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Journal of Nanoparticle Research

, 15:1888 | Cite as

Low density lipoproteins mediated nanoplatforms for cancer targeting

  • Anupriya Jain
  • Keerti Jain
  • Prashant Kesharwani
  • Narendra K. JainEmail author
Review

Abstract

Chemotherapy is a foremost remedial approach for the treatment of localized and metastasized tumors. In order to explore new treatment modalities for cancer, it is important to identify qualitative or quantitative differences in metabolic processes between normal and malignant cells. One such difference may be that of increased receptor-mediated cellular uptake of low density lipoproteins (LDLs) by cancer cells. Lipoproteins in general and specifically LDL are ideal candidates for loading and delivering cancer therapeutic and diagnostic agents due to their biocompatibility. By mimicking the endogenous shape and structure of lipoproteins, the reconstituted lipoproteins can remain in circulation for an extended period of time, while largely evading the reticuloendothelial cells in the body’s defenses. In this account, we review the field of low density inspired nanoparticles in relation to the delivery of cancer imaging and therapeutic agents. LDL has instinctive cancer targeting potential and has been used to incorporate various lipophillic molecules to transport them to tumors. Nature’s method of rerouting LDL provides a strategy to extend the cancer targeting potential of lipoproteins far off its constricted purview. In this review, we have discussed the various aspects of LDL including its role in cancer imaging and chemotherapy in retrospect and prospect and current efforts aimed to further improve the delivery efficacy of LDL–drug complexes with reduced chances of drug resistance leading to optimal drug delivery. This review provides a strong support for the concept of using LDL as a drug carrier.

Keywords

Lipoproteins Low density lipoprotein (LDL) Chemotherapy Drug carrier Targeted drug delivery 

Abbreviations

ABC-Transporters

ATP-Binding Cassette Transporter

ACAT

AcylCoA:Cholesterol Acyltransferase

Ac-LDL

Acetylated LDL

ACM

Aclacinomycin

ALL

Acute lymphocytic leukemia

AML

Acute myeloid leukemia

AP-2

Adaptin protein

Apo B-100

Apolipoprotein B-100

Apo E

Apolipoprotein E

bHLH-zip

Basic helix–loop–helix leucine zipper

BNCT

Boron neutron capture therapy

Ce6

Chlorin e6

CLA

Conjugated linoleic acid

COP-2 vesicle

Coat protein complex coated vesicle

COX-2

Cyclo-oxygenase 2

CT

Computed tomography

DIL

1,1′-Dioctyl-3,3,3′,3′-tetra methyl indocarbocyanide

DMEM

Dulbecco’s modified Eagle’s medium

DNM

Daunomycin

Dox

Doxorubicin

DpIUdR

3′,5′-O-dipalmitoyl-5-iodo-2′-deoxyuridine

DSC

Differential scanning calorimetry

ECM

Extracellular membrane

EDTA

Ethylene diamine tetra acetic acid

EGF

Epidermal growth factor

EM

Electron microscopy

FCR

Fractional clearance rate

FdUrd

Floxuridine

FRs

Folate receptors

HDL

High density lipoprotein

HepG2 cells

Human hepatoma cell line

HMGCoA reductase

3-Hydroxy-3-methylglutaryl coenzyme A reductase

ICAM-1

Intercellular adhesion molecule-1

INSIG 1/2

Insulin-induced gene1/2

LBNP

Lipoprotein-based nanoplatform

LDE

Low density emulsion

LDL

Low density lipoproteins

LDLR

Low density lipoprotein receptor

LHRH

Luteinizing hormone releasing hormone

MAPKs

Mitogen-activated protein kinases

Me-LDL

Methylated LDL

MRI

Magnetic resonance imaging

MTT

3(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

Nc

Napthocyanine

NIR

Near infra red imaging

NIRF

Near infra red imaging fluorophore

OL

Oleate

Ox-LDL

Oxidized LDL

PDT

Photodynamic therapy

PET

Positron emission tomography

PGE2

Prostaglandin E2

PKC

Protein kinase C

PS

Photosensitizer

Pz

Porphyrazine

RES

Reticulo endothelial system

RT-PCR

Reverse transcriptase polymerase chain reaction

SCAP

Sterol cleavage activating protein

SDS-PAGE

Sodium dodecyl sulphate polyacrylamide gel electrophoresis

SiNcBOA

Tetra-t-butyl silicon naphthalocyanine bisoleate

SiPcBOA

Tetra-t-butyl silicon phthalocyanine bearing two oleate moieties at its axial positions

SP1/2

Specific proteases1/2

SPECT

Single-photon emission computed tomography

SRE

Sterol regulatory element

SREBP

Sterol regulatory element binding protein

SSD

Sterol sensing domain

TNF

Tumor necrosis factor

VLDL

Very low density lipoprotein

Notes

Acknowledgments

The author Ms. Anupriya Jain is thankful to University Grant Commission (UGC), New Delhi, India for providing financial assistance in the form of Junior Research Fellowship (JRF) during this work.

References

  1. Anderson RGW, Brown MS, Goldstein JL (1977) The role of the coated endocytotic vesicle in the uptake of receptor bound low density lipoproteins in the human fibroblast cell. Cell 10:351–364Google Scholar
  2. Angelin B, Raviola CA, Innerarity TL, Mahley RW (1983) Rapid regulation of apolipoprotein B/E receptors, but not of apolipoprotein E receptors, by intestinal lipoproteins and bile acids. J Clin Invest 71:816–831Google Scholar
  3. Arias-Moreno X, Velazquez-Campoy A, Rodriguez JC, Pocov M, Sancho J (2008) Mechanism of low density lipoprotein (LDL) release in the endosome: implications of the stability and Ca2+ affinity of the fifth binding module of the LDL receptor. J Biol Chem 283:22670–22679Google Scholar
  4. Bachor R, Shea CR, Gillies R, Hasan T (1991) Photosensitized destruction of human bladder carcinoma cells treated with chlorin e6-conjugated microspheres. Proc Natl Acad Sci USA 88:1580–1584Google Scholar
  5. Bertato MP, Oliveira CP, Wajchenberg BL, Lerario AC, Maranhão RC (2012) Plasma kinetics of an LDL-like nanoemulsion and lipid transfer to HDL in subjects with glucose intolerance. Clinics (Sao Paulo) 67:347–353Google Scholar
  6. Bi WX, Xu SD, Zhang PH, Kong P (2000) Antitumoral activity of low density lipoprotein aclacinomycin complex in mice bearing H22 tumor. World J Gastroenterol 6:140–142Google Scholar
  7. Bien CM, Espenshade PJ (2010) Proteins in fungi: hypoxic transcription factors linked to pathogenesis. Eukaryot Cell 9:352–359Google Scholar
  8. Bijsterbosch MK, Van Berkel TJC (1990) Uptake of lactosylated low density lipoprotein by galactose-specific receptors in rat liver. Biochem J 270:233–239Google Scholar
  9. Bildstein L, Dubernet C, Couvreur P (2011) Prodrug-based intracellular delivery of anticancer agents. Adv Drug Deliv Rev 63:3–23Google Scholar
  10. Bilheimer DW, Grundy SM, Brown MS, Goldstein JS (1983) Mevinolin and colestipol stimulate receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes. Proc Natl Acad Sci USA 80:4124–4128Google Scholar
  11. Bozoky Z, Balogh L, Mathe D, Fulop L, Bertok L, Janoki GA (2004) Preparation and investigation of 99m technetium labeled low density lipoproteins in rabbits with experimentally induced hypercholesterolemia. Eur Biophys J 33:140–145Google Scholar
  12. Brown MS, Goldstein JL (1974) Familial hypercholesterolemia: defective binding of lipoproteins to cultured fibroblasts associated with impaired regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Proc Natl Acad Sci USA 71:788–792Google Scholar
  13. Brown MS, Goldstein JL (1986) A receptor-mediated pathway for cholesterol homeostasis. Science 232:34–47Google Scholar
  14. Brown MS, Goldstein JL (1994) A receptor-mediated pathway for cholesterol binding of anthracycline derivatives to human serum lipoproteins. Anticancer Res 14:2353–2355Google Scholar
  15. Brown MS, Goldstein JL (2009) Cholesterol feedback: from Schoenheimer’s bottle to Scap’s Meladl. J Lipid Res 50:S15–S27Google Scholar
  16. Brown MS, Brannan PG, Bohmfalk HA, Brunschede GY, Dana SE, Helgeson J, Goldstein JL (1975) Use of mutant fibroblasts in the analysis of the regulation of cholesterol metabolism in human cells. J Cell Physiol 85:425–436Google Scholar
  17. Callahan DE, Forte TM, Afzal SMJ, Deen DF, Kahl SB, Bjornstad KA, Bauer WF, Blakely EA (1991) Boronated protoporphyrin (BOPP): localization in lysosomes of the human glioma cell line SF-767 with uptake modulated by lipoprotein levels. Int J Radiat Oncol Biol Phys 3:488–495Google Scholar
  18. Caruso MG, Osella AR, Notarnicola M, Berloco P, Leo S, Bonfiglio C, Di Leo A (1998) Prognostic value of low density lipoprotein receptor expression in colorectal carcinoma. Oncol Rep 5:927–930Google Scholar
  19. Caruso MG, Notarnicola M, Cavallini A (2001) Low density lipoprotein receptor and mRNA expression in human colorectal cancer. Anticancer Res 21:429–433Google Scholar
  20. Caruso MG, Messa C, Orlando A, Attoma BD, Notarnicola M (2008) Early induction of LDL receptor gene expression by genistein in DLD-1 colon cancer cell line. Fitoterapia 79:524–528Google Scholar
  21. Cerda SR, Wilkinson J 4th, Broitman SA (1995) Regulation of cholesterol synthesis in four colonic adenocarcinoma cell lines. Lipids 30:1083–1092Google Scholar
  22. Chao FC, Efron B, Wolf P (1975) The possible prognostic usefulness of assessing serum proteins and cholesterol in malignancy. Cancer 35:1223–1229Google Scholar
  23. Chapman MJ (1980) Animal lipoproteins: chemistry, structure, and comparative aspects. J Lipid Res 21:789–853Google Scholar
  24. Chappell DA, Fry GL, Waknitz MA, Berns JJ (1991) Ligand size as a determinant for catabolism by the low density lipoprotein (LDL) receptor pathway: a lattice model for LDL binding. J Biol Chem 266:19296–19302Google Scholar
  25. Chassany O, Urien S, Claudepierre P, Bastian G, Tillement JP (1994) Binding of anthracyclines derivatives to human serum lipoproteins. Anticancer Res 14:2353–2355Google Scholar
  26. Chen Y, Hughes-Fulford M (2001) Human prostate cancer cells lack feedback regulation of low density lipoprotein receptor and its regulator, SREBP2. Int J Cancer 91:41–45Google Scholar
  27. Chu AC, Tsang SY, Lo EH, Fung KP (2001) Low density lipoprotein as a targeted carrier for doxorubicin in nude mice bearing human hepatoma HepG2 cells. Life Sci 70:591–601Google Scholar
  28. Chung NS, Wasan KM (2004) Potential role of the low-density lipoprotein receptor family as mediators of cellular drug uptake. Adv Drug Deliv Rev 56:1315–1334Google Scholar
  29. Ciftci K, Trovitch P (2003) Current approaches in the treatment of melanoma-II: immuno and gene therapy. Turk J Cancer 33:127–136Google Scholar
  30. Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, Hobbs HH (2005) Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet 37:161–165Google Scholar
  31. Corbin IR, Li H, Chen J, Lund-Katz S, Zhou R, Glickson JD, Zheng G (2006) Low-density lipoprotein nanoparticles as magnetic resonance imaging contrast agents. Neoplasia 8:488–498Google Scholar
  32. Corbin IR, Chen J, Cao W, Li H, Lund-Katz S, Zhou R, Glickson JD, Zheng G (2007) Enhanced cancer-targeted delivery using engineered high density lipoprotein based nanocarriers. J Biomed Nanotechnol 3:367–376Google Scholar
  33. Crich SG, Lanzardo S, Alberti D, Belfiore S, Ciampa A, Giovenzana GB, Lovazzano C, Pagliarin R, Aime S (2007) Magnetic resonance imaging detection of tumor cells by targeting low-density lipoprotein receptors with Gd-loaded low-density lipoprotein particles. Neoplasia 9:1046–1056Google Scholar
  34. Davis CG, Elhammer A, Russell DW, Schneider WJ, Kornfeld S, Brown MS, Goldstein JL (1986) Deletion of clustered O-linked carbohydrates does not impair function of low density lipoprotein receptor in transfected fibroblasts. J Biol Chem 261:2828–2838Google Scholar
  35. Davis CG, van Driel IR, Russell DW, Brown MS, Goldstein JL (1987) The low density lipoprotein receptor identification of amino acids in cytoplasmic domain required for rapid endocytosis. J Biol Chem 262:4075Google Scholar
  36. De Smidt PC, Van Berkel TJC (1990) Prolonged serum half-life of antineoplastic drugs by incorporation into the low density lipoprotein. Cancer Res 50:7476–7482Google Scholar
  37. Decker EA (1995) The role of phenolics, conjugated linoleic acid, carnosine, and pyrroloquinoline quinone as nonessential dietary antioxidants. Nutr Rev 53:49–58Google Scholar
  38. Deforge LE, Degalan MR, Ruyan MK, Newton RS, Raymond E (1992) Comparison of methods for incorporating a radioiodinated residualizing cholesteryl ester analog into low density lipoprotein. Int J Radiat Appl Instrum B 19:115–182Google Scholar
  39. Dehouck B, Dehouck MP, Fruchart JC, Cacchelli R (1994) Upregulation of low density lipoprotein receptor at blood brain barrier: intercommunication between brain capillary endothelial cells and astrocytes. J Cell Biol 126:465–473Google Scholar
  40. Dietschy JM, Woollett LA, Spady DK (1993) The interaction of dietary cholesterol and specific fatty acids in the regulation of LDL receptor activity and plasma LDL-cholesterol concentrations. Ann N Y Acad Sci 676:11–26Google Scholar
  41. Dougherty TJ (1989) Photodynamic therapy—new approaches. Semin Surg Oncol 5:6–16Google Scholar
  42. Eisenberg S, Windmueller HG, Levy RI (1973) Metabolic fate of rat and human lipoprotein apolipoproteins in the rat. J Lipid Res 14:446–458Google Scholar
  43. Eley JG, Halbert GW, Florence AT (1990a) Incorporation of prednimustine into low density lipoprotein: activity against P388 cells in tissue culture. Int J Pharm 65:219–224Google Scholar
  44. Eley JG, Halbert GW, Florence AT (1990b) The incorporation of estramustine into low density lipoprotein and its activity in tissue culture. Int J Pharm 63:121–127Google Scholar
  45. Fass D, Blacklow S, Kim PS, Berger JM (1997) Molecular basis of familial hypercholesterolemia from structure of LDL receptor module. Nature 388:691–693Google Scholar
  46. Favre G (1992) Targeting of tumor cells by low density lipoproteins: principle and use of ellipticine derivatives. C R Seances Soc Biol Fil 186:73–87Google Scholar
  47. Filipovic I, Buddecke E (1986) Calcium channel blockers stimulate LDL receptor synthesis in human skin fibroblasts. Biochem Biophys Res Commun 136:845–850Google Scholar
  48. Filippatos TD, Liberopoulos EN, Pavlidis N, Elisaf MS, Mikhailidis DP (2009) Effects of hormonal treatment on lipids in patients with cancer. Cancer Treat Rev 35:175–184Google Scholar
  49. Firestone RA (1994) Low density lipoprotein as a vehicle for targeting antitumor compounds to cancer cells. Bioconjug Chem 5:105–113Google Scholar
  50. Firestone RA, Pisano JM, Falck JR (1984) Selective delivery of cytotoxic compounds to cells by the LDL pathway. J Med Chem 27:1037–1043Google Scholar
  51. Folsch H, Ohno H, Bonifacino JS, Mellman I (1999) A novel clathrin adaptor complex mediates basolateral targeting in polarized epithelial cells. Cell 99:189–198Google Scholar
  52. Fox PL, DiCorleto PE (1986) Modified low density lipoproteins suppress production of a platelet-derived growth factor-like protein by cultured endothelial cells. Proc Natl Acad Sci USA 83:4774–4778Google Scholar
  53. Gal D, Ohashi M, MacDonald PC, Buchsbaum HJ, Simpson ER (1981) LDL as a potential vehicle for chemotherapeutic agents and radionucleotides in the management of gynecologic neoplasms. Am J Obstet Gynecol 139:877–885Google Scholar
  54. Garand C, Guay D, Sereduk C, Chow D, Tsofack SP, Langlois M, Perreault E, Yin HH, Lebel M (2011) An integrative approach to identity YB-1 interacting proteins required for cisplatin resistance in MCF and MDA-MB-231 breast cancer cells. Cancer Sci 102:1410–1417Google Scholar
  55. Geninatti-Crich S, Alberti D, Szabo I, Deagostino A, Toppino A, Barge A, Ballarini F, Bortolussi S, Bruschi P, Protti N, Stella S, Altieri S, Venturello P, Aime S (2011) MRI-guided neutron capture therapy by use of a dual gadolinium/boron agent targeted at tumour cells through upregulated low-density lipoprotein transporters. Chemistry 17:8479–8486Google Scholar
  56. Glickson JD (2005) Rerouting lipoprotein nanoparticles to selected alternate receptors for the targeted delivery of cancer diagnostic and therapeutic agents. Proc Natl Acad Sci USA 49:17757–17762Google Scholar
  57. Goldstein JL, Brown MS (1973) Familial hypercholesterolemia: identification of a defect in the regulation of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase activity associated with overproduction of cholesterol (cholesterol synthesis/hyperlipidemia/low density lipoproteins/enzyme regulation/coronary heart disease). Proc Natl Acad Sci USA 70:2804–2808Google Scholar
  58. Goldstein JL, Brown MS (2001) Molecular medicine. The cholesterol quartet. Science 292:1310–1312Google Scholar
  59. Goldstein JL, Brown MS (2009) The LDL receptor. Arterioscler Thromb Vasc Biol 29:431–438Google Scholar
  60. Goto D, Okimoto T, Ono M, Shimotsu H, Abe K, Tsujita Y, Kuwano M (1997) Upregulation of low density lipoprotein receptor by gemfibrozil, a hypolipidemic agent, in human hepatoma cells through stabilization of mRNA transcripts. Arteioscler Thromb Vasc Biol 17:2707–2712Google Scholar
  61. Gregoriades G, Wills EJ, Swain CP,  Tavill AS (1974) Drug carrier potential of liposomes in cancer chemotherapy. Lancet 1313–1316Google Scholar
  62. Grove RI, Mazzucco CE, Radika SF, Shoyab M, Kiener PA (1991) Oncostatin M up-regulates low density lipoprotein receptors in HepG2 cells by a novel mechanism. J Biol Chem 266:18194–18199Google Scholar
  63. Gueddari N, Favre G, Hachem H, Marek E, Gaillard FL, Soula G (1993) Evidence for up-regulated LDLR in human lung adenocarcinoma cell line A549. Biochimie 75:811–819Google Scholar
  64. Habenicht AJ, Salbach P, Goerig M, Zeh W, Janssen-Timmen U, Blattner C (1990) The LDL receptor pathway delivers arachidonic acid for eicosanoid formation in cells stimulated by platelet-derived growth factor. Nature (Lond) 345:634–636Google Scholar
  65. Hamanaka R, Kohno K, Seguchi T, Okamura K, Morimoto A, Ono M (1992) Transcription factor SP-1 by tumor necrosis factor in human microvascular endothelial cells. J Biol Chem 267:13160–13165Google Scholar
  66. Hamblin MR, Newman EL (1994) Photosensitizer targeting in photodynamic therapy. II. Conjugates of haematoporphyrin with serum lipoproteins. J Photochem Photobiol, B 26:147–157Google Scholar
  67. Handley DA, Arbeeny CM, Chien S (1980) Colloidal gold–low density lipoprotein conjugates as membrane receptor probes. Circulation 62:211Google Scholar
  68. Handley DA, Arbeeny CM, Eder HA, Chien S (1981) Hepatic binding and internalization of low density lipoprotein–gold conjugates in rats treated with 17α-ethinylestradiol. J Cell Biol 90:778–787Google Scholar
  69. Harada K, Shimano H, Kawakami M, Ishibashi S, Gotoda T, Mori N, Takaku F, Yamada N (1990) Effect of tumor necrosis factor/cachectin on the activity of the low density lipoprotein receptor on human skin fibroblasts. Biochem Biophys Res Commun 172:1022–1027Google Scholar
  70. Hasan T (1992) Photosensitizer delivery mediated by macromolecular carrier systems. In: Henderson B, Dougherty T (eds) Photodynamic therapy: basic principles and clinical applications. Marcel Dekker, New York, pp 187–200Google Scholar
  71. Hasan T, Parrish JA (1996) Photodynamic therapy of cancer. In: Holland JF (ed) Cancer medicine, 4th edn. Williams and Wilkins, Baltimore, pp 739–751Google Scholar
  72. Hay RV, Fleming RM, Ryan JW, Williams KA, Stark VJ, Stark VJ, Lathrop KA, Harper PV (1991) Nuclear imaging analysis of human low-density lipoprotein biodistribution in rabbits and monkeys. J Nucl Med 32:1239–1245Google Scholar
  73. He G, Gupta S, Yi M, Michaely P, Hobbs HH, Cohen JC (2002) ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2. J Biol Chem 277:44044–44049Google Scholar
  74. Henriksson P, Ericsson S, Stege R, Ericsson M, Rudling M, Berglund L, Angelin B (1989) Hypercholesterolemia and increased elimination of low density lipoprotein receptor activity in metastatic cancer of the prostate. Lancet 2:1178–1180Google Scholar
  75. Ho YK, Smith RG, Brown MS, Goldstein JL (1978) Low-density lipoprotein (LDL) receptor activity in human acute myelogenous leukemia cells. Blood 52:1099–1114Google Scholar
  76. Ho YK, Smith GR, Brown MS, Goldstein JL (1979) Low density lipoprotein (LDL) receptor activity in human acute myelogenous leukemia cells. Blood 56:1099–1114Google Scholar
  77. Horton JD, Goldstein JL, Brown MS (2002) SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 109:1125–1131Google Scholar
  78. Huang S, Henry L, Ho YK, Pownall HJ, Rudenko G (2010) Mechanism of LDL binding and release probed by structure-based mutagenesis of the LDL receptor. J Lipid Res 51:297–308Google Scholar
  79. Hynds SA, Welsh J, Stewart JM, Jack A, Soukop M, Mcardle CS, Calman KC, Packard CJ, Stephard J (1984) Low density lipoprotein metabolism in mice with soft tissue tumors. Biochim Biophys Acta 795:589–595Google Scholar
  80. Innerarity TL, Friedlander EJ, Rall SC Jr, Weisgraber KH, Mahley RW (1983) The receptor-binding domain of human apolipoprotein E. Binding of apolipoprotein E fragments. J Biol Chem 258:12341–12347Google Scholar
  81. Ip C, Dong Y, Ip MM, Banni S, Carta G, Angioni E, Murru E, Spada S, Melis MP, Saebo A (2002) Conjugated linoleic acid isomers and mammary cancer prevention. Nutr Cancer 43:52–58Google Scholar
  82. Jack RW, Michelle BM, Liang JW (1994) Low density lipoprotein as a transporter of dolichol intermediates in mammalian circulation. Biochem J 297:321–325Google Scholar
  83. Jasanda F, Urizzi P, Souchard JP, Le Gaillard F, Favre G, Nepveu F (1996) Indium-111 labeling of low density lipoproteins with the DTPA-bis (stearylamide): evaluation as a potential radiopharmaceutical for tumor localization. Bioconjug Chem 7:2–81Google Scholar
  84. Jeon H, Blacklow SC (2005) Structure and physiologic function of the low-density lipoprotein receptor. Annu Rev Biochem 74:535–562Google Scholar
  85. Jeon H, Meng W, Takagi J, Eck MJ, Springer TA, Blacklow SC (2001) Implications of familial hypercholesterolemia from the structure of the LDL receptor YWTD EGF domain pair. Nat Struct Biol 8:499–504Google Scholar
  86. Jiang FN, Allison B, Liu D, Levy JG (1991) Enhanced photodynamic killing of target cells by either monoclonal antibody or low density lipoprotein mediated delivery systems. J Control Release 19:41–58Google Scholar
  87. Jonnalagadda SC, Cruz JS, Connell RJ, Scottc PM, Mereddy VR (2009) Synthesis of α-carboranyl-α-acyloxy-amides as potential BNCT agents. Tetrahedron Lett 50:4314–4317Google Scholar
  88. Jori G (1989) In vivo transport and pharmacokinetic behaviour of tumour photosensitizers. In: Photosensitizing compounds: their chemistry, biology and clinical use, Ciba foundation symposium 146, Wiley, ChichesterGoogle Scholar
  89. Jori G (1990) Factors controlling the selectivity and efficiency of tumour damage of photodynamic therapy. Lasers Med Sci 5:115–120Google Scholar
  90. Jori G (1991) Low-density lipoproteins-liposome delivery systems for tumor photosensitizers in vivo. In: Henderson BW, Dougherty TJ (eds) Photodynamic therapy. Marcel Dekker, New York, pp 173–186Google Scholar
  91. Jori G, Reddi E (1993) Strategies for tumour targeting by photodynamic sensitizers. In: Kessel D (ed) Photodynamic therapy of neoplastic disease. CRC Press, Boca Raton, pp 117–130Google Scholar
  92. Jori G, Beltramini M, Reddi E, Pagnan A, Tomio L, Tsanov T (1984) Evidence for a major role of plasma lipoproteins as haematoporphyrin carriers in vivo. Cancer Lett 24:291–297Google Scholar
  93. Jung-Testas I, Weintraub H, Dupuis D, Eychenne B, Baulieu DE, Robel P (1992) Low density lipoprotein-receptors in primary cultures of rat glial cells. J Steroid Biochem Mol Biol 42:597–605Google Scholar
  94. Kader A, Pater A (2002) Loading anticancer drugs into HDL as well as LDL has little affect on properties of complexes and enhances cytotoxicity to human carcinoma cells. J Control Release 80:29–44Google Scholar
  95. Kader A, Davis PJ, Kara M, Liu H (1998) Drug targeting using low density lipoprotein (LDL): physicochemical factors affecting drug loading into LDL particles. J Control Release 55:231–243Google Scholar
  96. Kahl SB, Wainschel LA, Pate DW, Callaway JC, Hiltunen J (1993) In vitro and in vivo studies with boronated low density lipoproteins for neutron capture. In: Autrinen L, Kallio M (eds) Proceedings of clinical BNCT workshop, Helsinki, pp 105–109Google Scholar
  97. Kerr DJ, Hynds SA, Shepherd J, Packard CJ, Kaye SB (1988) Comparative cellular uptake and cytotoxicity of a complex of daunomycin-low density lipoprotein in human squamous lung tumour cell monolayers. Biochem Pharmacol 37:3981–3986Google Scholar
  98. Khan IU, Beck-Sickinger AG (2008) Targeted tumor diagnosis and therapy with peptide hormones as radiopharmaceuticals. Anticancer Agents Med Chem 8:186–199Google Scholar
  99. Kibbey RG, Rizo J, Gierasch LM, Anderson RG (1998) The LDL receptor clustering motif interacts with the clathrin terminal domain in a reverse turn conformation. J Cell Biol 142:59–67Google Scholar
  100. Kita T, Brown MS, Watanabe Y, Goldstein JL (1981) Deficiency of low density lipoprotein receptors in liver and adrenal gland of the WHHL rabbit, an animal model of familial hypercholesterolemia. Proc Natl Acad Sci USA 78:2268–2272Google Scholar
  101. Komizu Y, Ueoka H, Ueoka R (2012) Selective accumulation and growth inhibition of hybrid liposomes to human hepatocellular carcinoma cells in relation to fluidity of plasma membranes. Biochem Biophys Res Commun 418:81–86Google Scholar
  102. Kopecka J, Campia I, Olivero P, Pescarmona G, Ghigo D, Bosia A, Riganti C (2011) A LDL-masked liposomal-doxorubicin reverses drug resistance in human cancer cells. J Control Release 149:196–205Google Scholar
  103. Kovanen PT, Bilheimer DW, Goldstein JL, Jaramillo JL, Brown MS (1981) Regulatory role for hepatic low density lipoprotein receptors in vivo in the dog. Proc Natl Acad Sci USA 78:1194–1198Google Scholar
  104. Krieger M, Goldstein JL, Brown MS (1978) Receptor mediated uptake of low density lipoprotein reconstituted with 25-hydroxycholesteryl oleate suppresses 3-hydroxy-3-methylglutaryl-coenzymeA reductase and inhibits growth of human fibroblasts. Proc Natl Acad Sci USA 75:5052–5056Google Scholar
  105. Krieger M, Smith LC, Anderson RG (1979) Reconstituted low density lipoprotein: a vehicle for the delivery of hydrophobic fluorescent probes to cells. J Supramol Struct 10:467–478Google Scholar
  106. Kukowska-Latallo JF, Candido KA, Cao Z, Nigavekar SS, Majoros IJ, Thomas TP, Balogh LP, Khan MK, Baker JR Jr (2005) Nanoparticle targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer. Cancer Res 65:5317–5324Google Scholar
  107. Kumar A, Middleton A, Chambers TC, Mehta KD (1998) Differential roles of extracellular signal-regulated kinase-1/2 and p38 MAPK in interleukin-1b and tumor necrosis factor A-induced low density lipoprotein receptor expression in HepG2 cells. J Biol Chem 273:15742–15748Google Scholar
  108. Langer M, Beck-Sickinger AG (2001) Peptides as carrier for tumor diagnosis and treatment. Curr Med Chem Anticancer Agents 1:71–93Google Scholar
  109. Laster BH, Kahl SB, Popenoe EA, Pate DW, Fairchild RG (1991) Biological efficacy of boronated low density lipoprotein for boron neutron capture therapy as measured in cell culture. Cancer Res 51:4588–4593Google Scholar
  110. Lees AM, Lees RS (1991) 99m Technetium-labeled low density lipoprotein: receptor recognition and intracellular sequestration of radiolabel. J Lipid Res 32:1–8Google Scholar
  111. Leitersdorf E, Stein O, Stein Y (1985) Angiotensin II stimulates receptor-mediated uptake of LDL by bovine adrenal cortical cells in primary culture. Biochim Biophys Acta 835:183–190Google Scholar
  112. Lenka M, Eleanor AB, Kathleen AB, Dennis FD, Laura JK, Trudy MF (2000) Human glioblastoma cell lines: levels of low density lipoprotein receptor and low density lipoprotein receptor related Protein1. Cancer Res 60:2300–2303Google Scholar
  113. Leppala J, Kallio M, Nikula T, Nikkinen P, Liewendahl K, Jaaskelainen J, Savolainen S, Gylling H, Hiltunen J, Callaway J et al (1995) Accumulation of 99mTc-low-density lipoprotein in human malignant glioma. Br J Cancer 71:383–387Google Scholar
  114. Levy R, Jurwitz E, Maran R, Sela M (1975) The specific cytotoxic effects of daunomycin conjugated to antitumor antibodies. Cancer Res 35:1182–1186Google Scholar
  115. Li C, Kraemer FB, Ahlborn TE, Liu J (1999) Induction of low density lipoprotein receptor (LDLR) transcription by oncostatin M is mediated by the extracellular signal-regulated kinase signaling pathway and the repeat 3 element of the LDLR promoter. J Biol Chem 274:6747–6753Google Scholar
  116. Li H, Zhang Z, Blessington D, Nelson DS, Zhou R, Lund Katz S, Chance B, Glickson JD, Zheng G (2004) Carbocyanine labeled LDL for optical imaging of tumors. Acad Radiol 11:669–677Google Scholar
  117. Li H, Marotta DE, Kim S, Busch TM, Wileyto EP, Zheng G (2005) High payload delivery of optical imaging and photodynamic therapy agents to tumors using phthalocyanine-reconstituted low density lipoprotein nanoparticles. J Biomed Opt 10:41203Google Scholar
  118. Liao W, Floren CH (1993) Tumor necrosis factor up-regulates expression of low-density lipoprotein receptors on HepG2 cells. Hepatol 17:898–907Google Scholar
  119. Liao W, Floren CH (1994) Upregulation of Low density lipoprotein receptor activity by tumor necrosis factor, a process independent of tumor necrosis factor induced lipid synthesis and secretion. Lipid 29:679–684Google Scholar
  120. Lindgren V, Luskey KL, Russel DW, Francke U (1985) Human genes involved in cholesterol metabolism: chromosomal mapping of the loci for the low density lipoprotein receptor and 3-hydroxy-3methylglutayl-coenzyme A reductase with cDNA probes. Proc Natl Acad Sci USA 82:8567–8571Google Scholar
  121. Lohse S, Derer S, Beyer T, Klausz K, Peipp M, Leusen JH, van de Winkel JG, Dechant M, Valerius T (2011) Recombinant dimeric IgA antibodies against the epidermal growth factor receptor mediate effective tumor cell killing. J Immunol 186:3770–3778Google Scholar
  122. Lum DF, McQuaid KR, Gilbertson VL, Hughes-Fulford M (1999) Coordinate up-regulation of low-density lipoprotein receptor and cyclo-oxygenase-2 gene expression in human colorectal cells and in colorectal adenocarcinoma biopsies. Int J Cancer 83:162–166Google Scholar
  123. Lundberg B (1987) Preparation of drug-low density lipoprotein complexes for delivery of antitumoral drugs via the low density lipoprotein pathway. Cancer Res 47:4105–4108Google Scholar
  124. Lundberg B (1992) Assembly of prednimustine low-density lipoprotein complexes and their cytotoxic activity in tissue culture. Cancer Chemo Pharm 29:241–247Google Scholar
  125. Lundberg B, Suominen L (1984) Preparation of biologically active analogs of serum low density lipoprotein. J Lipid Res 25:550–558Google Scholar
  126. Lund-Katz S, Laplaud PM, Phillips MC (1998) Apo lipoprotein B-100 conformation and particle surface charge in human LDL subspecies: implication for LDL receptor interaction. Biochemistry 37:12867–12874Google Scholar
  127. Lyon RP, Meyer DL, Setter JR, Senter PD (2012) Conjugation of anticancer drugs through endogenous monoclonal antibody cysteine residues. Methods Enzymol 502:123–138Google Scholar
  128. Mack JT, Townsend DM, Beljanski V, Tew KD (2007) The ABCA2 transporter: intracellular roles in trafficking and metabolism of LDL-derived cholesterol and sterol-related compounds. Curr Drug Metab 8:47–57Google Scholar
  129. Maletinska L, Blakely EA, Bjornstad KA, Deen DF, Knoff LJ, Forte TM (2000) Human glioblastoma cell lines: levels of low density lipoprotein receptor and low density receptor related protein. Cancer Res 60:2300–2303Google Scholar
  130. Manzoni C, Durati M, Eberini I, Schamag H, Marz W, Castiglioni S, Lovati MR (2003) Subcellular localization of soyabean 7s Globulin in HepG2 cell and LDL receptor up-regulation by its α-constituent subunit. J Nutr 133:2149–2155Google Scholar
  131. Maranhao RC, Gariochea B, Silva EL, Dorhiac-Llacer P, Cadena SMS, Coelho IJC (1994) Plasma kinetics and biodistribution of a lipid emulsion resembling low density lipoprotein in patients with acute leukemia. Cancer Res 54:4660–4666Google Scholar
  132. Masquelier M, Vitols S, Peterson C (1986) Low-density lipoprotein as a carrier of antitumoral drugs: in vivo fate of drug-human low-density lipoprotein complexes in mice. Cancer Res 46:3842–3847Google Scholar
  133. Masquelier M, Vitols S, Son MP, Marsc U, Larssonc BS, Peterson VDC (2000) Low density lipoprotein as a carrier of cytostatics in cancer chemotherapy: study of stability of drug-carrier complexes in blood. J Drug Target 8:155–161Google Scholar
  134. Maurer ME, Cooper JA (2006) The adaptor protein Dab2 sorts LDL receptors into coated pits independently of AP-2 and ARH. J Cell Sci 119:4235–4246Google Scholar
  135. Maziere JC, Santus R, Morliere P, Reyftmann JP, Candide C, Mora L, Salmon S, Maziere C, Gatt S, Dubertret L (1990) Cellular uptake and photosensitizing properties of anticancer porphyrins in cell membranes and low and high density lipoproteins. J Photochem Photobiol 6:61–68Google Scholar
  136. Medoza FJ, Espino SP, Cann KL, Bristow N, McCrea K, Los M (2005) Anti-tumor chemotherapy utilizing peptide-based approaches—apoptotic pathways, kinases, and proteasome as targets. Arch Immunol Ther Exp 53:47–60Google Scholar
  137. Mew D, Wat CK, Towers GHN, Levy JG (1983) Photoimmunotherapy: treatment of animal tumors with tumor specific monoclonal antibody haematoporphyrin conjugate. J Immunol 130:1473–1477Google Scholar
  138. Miller SR, Tartter PI, Papatestas AE, Slater G, Aufses AH (1981) Serum cholesterol and human colon cancer. J Natl Cancer Inst 67:297–300Google Scholar
  139. Moerlein SM, Daugherty A, Sobel BE, Welch MJ (1991) Metabolic imaging with gallium-68- and indium-111-labeled low-density lipoprotein. J Nucl Med 32:300–307Google Scholar
  140. Mosley ST, Goldstein JL, Brown MS, Falck JR, Anderson RGW (1981) Targeted killing of cultured cells by receptor-dependent photosensitization. Proc Natl Acad Sci USA 78:5717–5721Google Scholar
  141. Murakami M, Yshio Y, Mihara Y, Kuratsu J, Horiuchi S, Morino Y (1990) Cholesterol uptake by human glioma cells via receptor-mediated endocytosis of low-density lipoprotein. J Neurosurg 73:760–767Google Scholar
  142. Murakami S, Nitanai I, Uchida S, Konda-ohta Y, Asami Y, Kondo K, Sato M, Kawashima A, Hara H, Tomisawa K, Mei HB, Xiang CZ (1999) Up-regulation of low density lipoprotein receptor by a novel isobenzofranone derivative, MD-700. Artherosclerosis 146:281–290Google Scholar
  143. Ng KK, Lovell JF, Zheng G (2011) Lipoprotein inspired nanoparticles for cancer theranostics. Acc Chem Res 44:1105–1113Google Scholar
  144. Nicholson AC, Hajjar DP (1992) Transforming growth factor-α upregulates low density lipoprotein receptor mediated cholesterol metabolism in vascular smooth muscle cells. J Biol Chem 267:25982–25987Google Scholar
  145. Niendorf A, Nagele H, Gerding D, Meyer-Pannwitt U, Gebhardt A (1995) Increased LDL receptor mRNA expression in colon cancer is correlated with a rise in plasma cholesterol levels after curative surgery. Int J Cancer 61:461–464Google Scholar
  146. Norata G, Canti G, Ricci L, Nicolin A, Trezzi E, Catapano AL (1984) In vivo assimilation of low density lipoproteins by a fibrosarcoma tumour line in mice. Cancer Lett 25:203–208Google Scholar
  147. Notarnicola M, Messa C, Pricci M, Guerra V, Altomare DF, Montemurro S, Caruso MG (2004) Upregulation of 3-hydroxy-3-methylglutaryl coenzyme a reductase activity in left-sided human colon cancer. Anticancer Res 24:3837–3842Google Scholar
  148. Paterson HI, Appergren K (1973) Experimental studies on the uptake and retention of labelled proteins in a rat tumor. Eur J Cancer 9:109–116Google Scholar
  149. Pinheiro KV, Hungria VT, Ficker ES, Valduga CJ, Mesquita CH, Maranhao RC (2002) Plasma kinetics of a cholesterol-rich microemulsion (LDE) in patients with Hodgkin’s and non-Hodgkin’s lymphoma and a preliminary study on the toxicity of etoposide associated with LDE. Cancer Chemother Pharmacol 57:624–630Google Scholar
  150. Pinzón-Daza M, Garzón R, Couraud P, Ia Romero, Weksler B, Ghigo D, Bosia A, Riganti C (2012) The association of statins plus LDL receptor-targeted liposome-encapsulated doxorubicin increases in vitro drug delivery across blood–brain barrier cells. Br J Pharmacol 167:1431–1447Google Scholar
  151. Pires LA, Hegg R, Freitas ER, Tavares ER, Almeida CP, Baracat EC, Maranhão RC (2012) Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer. Braz J Med Biol Res 45:557–564Google Scholar
  152. Pitas RE, Boyles JK, Lee SH, Hui D, Weisgraber KH (1981a) Lipoproteins and their receptors in the central nervous system. J Biol Chem 262:14352–14360Google Scholar
  153. Pitas RE, Innerarity TL, Weinstein JN, Mahley RW (1981b) Acetoacetylated lipoproteins used to distinguish fibroblasts from macrophages in vitro by fluorescence microscopy. Arteriosclerosis 1:177–185Google Scholar
  154. Pitas RE, Boyles J, Mahley RW, Bissell DM (1985) Uptake of chemically modified low density lipoproteins in vivo is mediated by specific endothelial cells. J Cell Biol 100:103–117Google Scholar
  155. Pittman RC, Attie AD, Carew TE, Steinberg D (1979) Tissue site of degradation of low density lipoprotein: application of a method for determining fate of plasma proteins. Proc Natl Acad Sci USA 76:5345–5349Google Scholar
  156. Pluen A, Boucher Y, Ramanujan S, McKee TD, Gohongi T, di Tomaso E, Brown EB, Izumi Y, Campbell RB, Berk DA, Jain RK (2001) Role of tumor host interactions in interstitial diffusion of macromolecules: cranial vs. subcutaneous tumors. Proc Natl Acad Sci USA 98:4628–4633Google Scholar
  157. Ponec M, Havekes L, Kempennar J, Vermeer BJ (1984) Defective LDL metabolism in cultured normal, transformed, and malignant keratinocytes. J Invest Dermol 83:436–440Google Scholar
  158. Ponti M, Forrow SM, Souhami RL, D’Incalci M, Hartley JA (1991) Measurement of the sequence specificity of covalent DNA modification by antineoplastic agents using Taq DNA polymerase. Nucleic Acids Res 19:2929–2933Google Scholar
  159. Pritchard KI (2009) Ovarian suppression/ablation in premenopausal ER-positive breast cancer patients: issues and recommendations. Oncol 23:27–33Google Scholar
  160. Rai P, Mallidi S, Zheng X, Rahmanzadeh R, Mir Y, Elringtona S, Khurshid A, Hasan T (2010) Development and applications of photo-triggered theranostic agents. Adv Drug Deliv Rev 62:1094–1124Google Scholar
  161. Reihner E, Angelin B, Rudling M, Ewerth S, Bjorkhem I, Einarsson K (1990) Regulation of hepatic cholesterol metabolism in humans: stimulatory effects of cholestyramine on HMG-CoA reductase activity and low density lipoprotein receptor expression in gallstone patients. J Lipid Res 31:2219–2226Google Scholar
  162. Rensen PC, Vrueh RL, Kuiper J (2001) Recombinant lipoproteins: lipoprotein-like lipid particles for drug targeting. Adv Drug Deliv Rev 47:251–276Google Scholar
  163. Reza JZ, Nikzamir A, Doosti M, Pour MS (2010) A modification method for isolation and acetylation of low density lipoprotein of human plasma by density discontinuous gradient ultracentrifugation. J Biol Sci 10:785–789Google Scholar
  164. Roberts WG, Hasan T (1993) Tumor secreted vascular permeability factor influences photosensitizer uptake. Cancer Res 53:1–5Google Scholar
  165. Rudenko G, Henry L, Henderson K, Ichtchenko K, Brown MS, Goldstein JL, Deisenhefer J (2002) Structure of the LDL receptor extracellular domain at endosomal pH. Science 298:2353–2358Google Scholar
  166. Rudling MJ, Collins VP, Peterson CO (1983) Delivery of aclacinomycin A to human glioma cells in vitro by the low-density lipoprotein pathway. Cancer Res 43:4600–4605Google Scholar
  167. Rudling MJ, Angelin B, Peterson CO, Collins VP (1990) Low density lipoprotein receptor activity in human intracranial tumors and its relation to cholesterol requirement. Cancer Res 50:483–487Google Scholar
  168. Russell DW, Schneider WJ, Kamamoto T, Luskey K, Brown M, Goldstein JL (1984) Domain map of the LDL receptor: sequence homology with the epidermal growth factor precursor. Cell 37:577–585Google Scholar
  169. Samadi-Baboli M, Favre G, Blancy E, Soula G (1989) Preparation of low density lipoprotein-9 methoxy ellipticin complex and its cytotoxic effect against L1210 and P388 leukemic cells in vitro. Eur J Cancer Oncol 25:233–241Google Scholar
  170. Samadi-Baboli M, Favre G, Bernadou J, Berg D, Soula G (1990) Comparative study of the incorporation of ellipticin-esters into low density lipoprotein (LDL) and selective cell uptake of drug-LDL complex via the LDL receptor pathway in vitro. Biochem Pharmacol 40:203–212Google Scholar
  171. Samadi-Baboli M, Favre G, Canal P, Soula G (1993) Low density lipoprotein for cytotoxic drug targeting: improved activity of elliptinium derivative against B16 melanoma in mice. Br J Cancer 68:319–326Google Scholar
  172. Schally AV, Nagy A (1999) Cancer chemotherapy based on targeting of cytotoxic peptide conjugates to their receptors on tumors. Eur J Endocrinol 141:1–14Google Scholar
  173. Schally AV, Nagy A (2004) Chemotherapy targeted to cancers through tumoral hormone receptors. Trends Endocrinol Metab 15:300–310Google Scholar
  174. Schmidt-Erfurth U, Bauman W, Gragoudas E, Flotte TJ, Michaud NA, Bimgruber R, Hasan T (1994) Photodynamic therapy of experimental choroidal melanoma using lipoprotein-delivered benzoporphyrin. Ophthalmology 101:89–99Google Scholar
  175. Schmidt-Erfurth U, Diddens H, Birngruber R, Hasan T (1997) Photodynamic targeting of human retinoblastoma cells using covalent low density lipoprotein conjugates. Br J Cancer 75:54–61Google Scholar
  176. Segrest JP, Jones MK, Loof HD, Dashti N (2002) Structure of apolipoprotein B-100 in low density lipoproteins. J Lipid Res 42:1346–1367Google Scholar
  177. Sekar N, Veldhuis JD (2004) Involvement of Sp1 and SREBP-1a in transcriptional activation of the LDL receptor gene by insulin and LH in cultured porcine granulosa-luteal cells. Am J Physiol Endocrinol Metab 287:E128–E135Google Scholar
  178. Seki J, Okita A, Watanabe M, Nakagawa T, Honda K, Tatewaki N (1985) Plasma lipoproteins as drug carriers: pharmacological activities and disposition of the complex of β-sitosteryl-β-d-glucopyranoside with plasma lipoproteins. J Pharm Sci 74:1259–1264Google Scholar
  179. Setiawan Y, Moore DE, Allen BJ (1996) Selective uptake of boronated low-density lipoprotein in melanomaxenografts achieved by diet supplementation. Br J Cancer 74:1705–1708Google Scholar
  180. Shaomei YP, Dezhong Y, Guixiang Z, Kris-Etherton PM, Etherton TD (2004) Conjugated linoleic acid upregulates LDL receptor gene expression in HepG2 cells. J Nutr 134:68–71Google Scholar
  181. Shaw MK, Newton RS, Sliskovic DR, Roth BD, Ferguson E, Krause BR (1990) Hep-G2 cells and primary rat hepatocytes differ in their response to inhibitors of HMG-CoA reductase. Biochem Biophys Res Commun 170:726–734Google Scholar
  182. Sher J, Pronczuk A, Hajri T, Hayes KC (2003) Dietary conjugated linoleic acid lowers plasma cholesterol during cholesterol supplementation, but accentuates the atherogenic lipid profile during the acute phase response in hamsters. J Nutr 133:456–460Google Scholar
  183. Sherlock S (1995) Alcoholic liver disease. Lancet 345:227–229Google Scholar
  184. Shimano H, Aburatani H, Mori N, Ishibashi S, Gotohda T, Mokuno H, Kawakami M, Akanuma Y, Takaku F, Murase T et al (1988) Downregulation of hepatic LDL receptor protein and messenger RNA in fasted rabbits. J Biochem 104:712–716Google Scholar
  185. Simon N, Dailly E, Jolliet P, Tillement JP, Urien S (1997) pH dependent binding of ligands to serum lipoproteins. Pharm Res 14:527–532Google Scholar
  186. Song L, Li H, Sunar U, Chen J, Corbin I, Yodh AG, Zheng G (2007) Naphthalocyanine reconstituted LDL nanoparticles for in vivo cancer imaging and treatment. Int J Nanomed 2:767–774Google Scholar
  187. Spady DK, Dietschy JM (1985) Dietary saturated triacylglycerols suppress hepatic low-density lipoprotein receptor activity in the hamster. Proc Natl Acad Sci USA 82:4526–4530Google Scholar
  188. Sreekanth CN, Bava SV, Sreekumar E, Anto RJ (2011) Molecular evidences for the chemosensitizing efficacy of liposomal curcumin in paclitaxel chemotherapy in mouse models of cervical cancer. Oncogene 30:3139–3152Google Scholar
  189. Stein O, Weinstein Y, Steinberg D (1976) Binding, internalization and degradation of low density lipoprotein by normal human fibroblasts and by fibroblasts from a case of homozygous familial hypercholesterolemia (cell membrane receptors/cholesterol biosynthesis). Biochemistry 73:14–18Google Scholar
  190. Steiniger SCJ, Kreuter J, Khalansky AS, Skidan IN, Bobruskin AI, Smirnova ZS, Severin SE, Uhl R, Kock M, Geiger KD, Gelperina SE (2004) Chemotherapy of glioblastoma in rats using doxorubicin-loaded nanoparticles. Int J Cancer 109:759–767Google Scholar
  191. Stephan ZF, Yurachek EC (1993) Rapid fluorometric assay of LDL receptor activity by DiI-labeled LDL. J Lipid Res 34:325–330Google Scholar
  192. Stranzl A, Schmidt H, Winkler R, Kostner GM (1997) Low-density lipoprotein receptor mRNA in human breast cancer cells: influence by PKC modulators. Breast Cancer Res Treat 42:195–205Google Scholar
  193. Streicher R, Kotzka J, Muller-Wieland D, Siemeister G, Munck M, Avci H, Krone W (1996) SREBP-1 mediates activation of the low density lipoprotein receptor promoter by insulin and insulin like growth factor. J Biol Chem 271:7128–7133Google Scholar
  194. Streicher J, Valent P, Schmidt H, Sengolge G, Wagner O, Strobl W, Hörl WH, Derfler K (1999) Up-regulation of LDL-receptor expression by LDL-immunoapheresis in patients with familial hypercholesterolemia. J Invest Med 47:378–387Google Scholar
  195. Suareza Y, Fernandez C, Gomez-Coronado D, Ferrueloa AJ, Davalos A, Martinez-otasa J, Lasunción MA (2004) Synergistic upregulation of low density lipoprotein receptor activity by tamoxifen and lovastatin. Cardiol Res 64:346–355Google Scholar
  196. Sullivan DC, Ferrari M (2004) Nanotechnology and tumor imaging: seizing an opportunity. Mol Imaging 3:364–369Google Scholar
  197. Tokui T, Kuroiwa C, Muramatsu S, Tokui Y, Sasagawa K, Ikeda T, Komai T (1995) Plasma lipoproteins as targeting carriers to tumour tissues after administration of a lipophilic agent to mice. Biopharm Drug Dispos 16:91–103Google Scholar
  198. Trivedi ER, Harney AS, Olive MB, Podgorski I, Moin K, Sloane BF, Barrett AG, Meade TJ, Hoffman BM (2010a) Chiral porphyrazine near-IR optical imaging agent exhibiting preferential tumor accumulation. Proc Natl Acad Sci USA 107:1284–1288Google Scholar
  199. Trivedi ER, Vesper BJ, Weitman H, Ehrenberg B, Barrett AG, Radosevich JA, Hoffman BM (2010b) Chiral bis-acetal porphyrazines as near-infrared optical agents for detection and treatment of cancer. Photochem Photobiol 86:410–417Google Scholar
  200. Trouet A, Deprez-de Campeneere D, De Duve C (1972) Chemotherapy through lysosomes with DNA–daunorubicin complexes. Nature (Lond) 239:110–112Google Scholar
  201. Urizzi P, Souchard JP, Palevody C, Ratovo G, Hollande E, Nepveu F (1997) Internalization of indium-labeled LDL through a lipid chelating anchor in human pancreatic cancer cells as a potential radiopharmaceutical for tumor localization. J Cancer 70:315–322Google Scholar
  202. Vallabhajosula S, Goldsmith SJ (1990) 99mTc-low density lipoprotein: intracellularly trapped radiotracer for noninvasive imaging of low density lipoprotein metabolism in vivo. Semin Nucl Med 20:68–79Google Scholar
  203. Van Hillegersberg R, Kort WJ, Wilson JH (1994) Current status of photodynamic therapy in oncology. Drugs 48:510–527Google Scholar
  204. Vermeer BJ, Wijsman MC, Mommaas-Kienhuis AM, Ponec M, Havekes L (1985) Modulation of LDL receptor activity in squamous carcinoma cells by variation in cell density. Eur J Cell Biol 300:353–369Google Scholar
  205. Versluis AJ, Van Geel PJ, Oppelaar H, Van Berkel TJ, Bijsterbosch MK (1996) Receptor-mediated uptake of low-density lipoprotein by B16 melanoma cells in vitro and in vivo in mice. Br J Cancer 74:525–532Google Scholar
  206. Vitols S (1991) Uptake of low density lipoprotein by malignant cells: possible therapuetic applications. Cancer Cell 3:488–495Google Scholar
  207. Vitols S, Gahrton G, Ost A, Peterson C (1984a) Elevated low density lipoprotein receptor activity in leukaemic cells with monocytic differentiation. Blood 63:1186–1193Google Scholar
  208. Vitols S, Gahrton G, Peterson C (1984b) Significance of the low-density lipoprotein receptor pathway for the in vitro accumulation of AD-32 incorporated into LDL in normal and leukemic white blood cells. Cancer Treat Rep 68:515–520Google Scholar
  209. Vitols S, Gahrton G, Bjorkholm M, Peterson C (1985) Hypercholesterolemia in malignancy due to elevated low density lipoprotein receptor activity in tumor cells: evidence from studies in patients with leukemia. Lancet 2:1150–1153Google Scholar
  210. Vitols S, Angelin B, Ericsson S, Gahrton G, Juliusson G, Masquelier M, Paul C, Peterson C, Rudling M, Söderberg-Reid K et al (1990) Uptake of low density lipoproteins by human leukemic cells in vivo: relation to plasma lipoprotein levels and possible relevance for selective chemotherapy. Proc Natl Acad Sci USA 87:2598–2602Google Scholar
  211. Vitols S, Peterson C, Larsson O, Holm P, Aberg B (1992) Elevated uptake of low density lipoproteins by human lung cancer tissue in vivo. Cancer Res 52:6244–6247Google Scholar
  212. Walker AK, Jacobs RL, Watts JL, Rottiers V, Jiang K, Finnegan DM, Shioda T, Hansen M, Yang F, Niebergall LJ, Vance DE, Tzoneva M, Hart AC, Näär AM (2011) A conserved SREBP1/phosphatidylcholine feedback circuit regulates lipogenesis in metazoans. Cell 47:840–852Google Scholar
  213. Wall ME, Abernathy GS, Carrol FI, Taylor DJ (1969) The effects of some steroidal alkylating agents on experimental animal mammary tumor and leukemia systems. J Med Chem 12:810–818Google Scholar
  214. Wasan KM, Brocks DR, Lee SD, Sachs-Barrable K, Thornton SJ (2008) Impact of lipoproteins on the biological activity and disposition of hydrophobic drugs: implications for drug discovery. Nat Rev Drug Discov 7:84–99Google Scholar
  215. Weishaupt UR, Gomer CJ, Dougherty TJ (1976) Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumour. Cancer Res 36:2326–2329Google Scholar
  216. Williams CD, Avigan J (1972) In vitro effects of serum proteins and lipids on lipid synthesis in human skin fibroblasts and leukocytes grown in culture. Biochim Biophys Acta 260:413–423Google Scholar
  217. Yamamoto T, Davis CG, Brown MS, Schneider WJ, Casey ML, Goldstein JL, Russell DW (1984) The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA. Cell 39:27–38Google Scholar
  218. Yanovich S, Preston L, Shaw JM (1984) Characteristics of uptake and cytotoxicity of a low-density lipoprotein–daunomycin complex in P388 leukemic cells. Cancer Res 44:3377–3382Google Scholar
  219. Yeung TCH, Yang L, Huang Y, Wang J, Chen ZY (2000) Dietary conjugated linoleic acid mixture affects the activity of intestinal acyl coenzyme A: cholesterol acyltransferase in hamsters. Br J Nutr 84:935–941Google Scholar
  220. Yu N, Wang M (2008) Anticancer drug discovery targeting DNA hypermethylation. Curr Med Chem 15:1350–1375Google Scholar
  221. Zhang Z, Chen J, Ding L, Jin H, Lovell JF, Corbin IR, Cao W, Lo PC, Yang M, Tsao MS, Luo Q, Zheng G (2010) HDL-mimicking peptide-lipid nanoparticles with improved tumor targeting. Small 6:430–437Google Scholar
  222. Zheng G, Li H, Yang K, Blessington D, Licha K, Lund-Katz S, Chance B, Glickson JD (2002) Tricarbocyanine cholesteryl laurates labeled LDL: new near infrared fluorescent probes (NIRFs) for monitoring tumors and gene therapy of familial hypercholesterolemia. Bioorg Med Chem Lett 12:1485–1488Google Scholar
  223. Zheng G, Chen J, Li H, Glickson JD (2005) Rerouting lipoprotein nanoparticles to selected alternate receptors for the targeted delivery of cancer diagnostic and therapeutic agents. Proc Natl Acad Sci USA 102:17757–17762Google Scholar
  224. Zwaka TP, Hombach V, Torzewski J (2001) C-Reactive protein-mediated low density lipoprotein uptake by macrophages implications for atherosclerosis. Circulation 103:1194–1197Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Anupriya Jain
    • 1
  • Keerti Jain
    • 1
  • Prashant Kesharwani
    • 1
  • Narendra K. Jain
    • 1
    Email author
  1. 1.Pharmaceutics Research Laboratory, Department of Pharmaceutical SciencesDr. H. S. Gour UniversitySagarIndia

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