Journal of Chemical Biology

, Volume 6, Issue 1, pp 7–23 | Cite as

Strategies to target tumors using nanodelivery systems based on biodegradable polymers, aspects of intellectual property, and market

  • Michele F. Oliveira
  • Pedro P. G. Guimarães
  • Alinne D. M. Gomes
  • Diego Suárez
  • Rubén D. Sinisterra


Cancer Nanodelivery systems Biodegradable polymers Targeting Intellectual property 




A10 RNA aptamer

A10 2′-fluoropyrimidine RNA aptamer


Adrenocorticotropin hormone


Corticotropin releasing factor






1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride


Enhanced permeability and retention


Folic acid


Human epidermal receptors


Magnetic resonance imaging






Platelet-derived growth factor receptor


Poly(ethylene glycol)


Positron emission tomography


Poly(glycolic acid)


Poly(lactic acid)






Prostate-specific membrane antigen


Small interfering RNA


Single photon emission computed tomography


d-α-tocopheryl polyethylene glycol succinate


Vascular cell adhesion molecule-1


Endothelial growth factor receptors


Wheat germ agglutinin


  1. 1.
    Hamdy S, Haddadi A, Hung RW, Lavasanifar A (2011) Targeting dendritic cells with nano-particulate PLGA cancer vaccine formulations. Adv Drug Deliv Rev 63(10–11):943–955CrossRefGoogle Scholar
  2. 2.
    Shen H, You J, Zhang G, Ziemys A, Li Q, Bai L, Deng X, Erm DR, Liu X, Li C, Ferrari M (2012) Cooperative, nanoparticle-enabled thermal therapy of breast cancer. Adv Healthc Mater 1(1):84–89. doi:10.1002/adhm.201100005 CrossRefGoogle Scholar
  3. 3.
    WHO (2008) Accessed 21 March 2012
  4. 4.
    Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2(3):161–174CrossRefGoogle Scholar
  5. 5.
    Ferguson TA, Choi J, Green DR (2011) Armed response: how dying cells influence T-cell functions. Immunol Rev 241:77–88CrossRefGoogle Scholar
  6. 6.
    Veiseh O, Kievit FM, Ellenbogen RG, Zhang M (2011) Cancer cell invasion: treatment and monitoring opportunities in nanomedicine. Adv Drug Deliv Rev 63(8):582–596CrossRefGoogle Scholar
  7. 7.
    Barton CL (2011) Innovations in the delivery of cancer therapies. Business InsightsGoogle Scholar
  8. 8.
    Chabner BA, Roberts TG (2005) Timeline—chemotherapy and the war on cancer. Nat Rev Cancer 5(1):65–72. doi:10.1038/nrc1529 CrossRefGoogle Scholar
  9. 9.
    Lewis LD (2006) Cancer pharmacotherapy: 21st century ‘magic bullets’ and changing paradigms. Br J Clin Pharmacol 62(1):1–4. doi:10.1111/j.1365-2125.2006.02721.x CrossRefGoogle Scholar
  10. 10.
    Teixeira LA, Fonseca CO (2007) De doença desconhecida a problema de saúde pública: o INCA e o controle do câncer no Brasil. Acessed 28 Aug 2012
  11. 11.
    ACS (2012) Accessed 10 Jan 2012
  12. 12.
    Rosenberg B, Camp L, Grimley E, Thomson A (1967) The inhibition of growth or cell division in Escherichia coli by different ionic species of platinum (IV) complexes. J Biol Chem 242(25):1347–1352Google Scholar
  13. 13.
    Wang D, Lippard SJ (2005) Cellular processing of platinum anticancer drugs. Nat Rev Drug Discov 4(4):307–320. doi:10.1038/nrd1691 CrossRefGoogle Scholar
  14. 14.
    Zhang CX, Lippard SJ (2003) New metal complexes as potential therapeutics. Curr Opin Chem Biol 7(4):481–489CrossRefGoogle Scholar
  15. 15.
    Ferrari M (2005) Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer 5(3):161–171. doi:10.1038/nrc1566 CrossRefGoogle Scholar
  16. 16.
    Guo J, Bourre L, Soden DM, O’Sullivan GC, O’Driscoll C (2011) Can non-viral technologies knockdown the barriers to siRNA delivery and achieve the next generation of cancer therapeutics? Biotechnol Adv 29(4):402–417CrossRefGoogle Scholar
  17. 17.
    Haile S (2008) Cancer metastasis and in vivo dissemination of tissue-dwelling pathogens: extrapolation of mechanisms and exchange of treatment strategies thereof. Med Hypotheses 70(2):375–377CrossRefGoogle Scholar
  18. 18.
    Rowinsky E, Donehower R (1995) Paclitaxel (Taxol). N Engl J Med 332(15):1004–1014CrossRefGoogle Scholar
  19. 19.
    Soppimath KS, Liu LH, Seow WY, Liu SQ, Powell R, Chan P, Yang YY (2007) Multifunctional core/shell nanoparticles self-assembled from pH-induced thermosensitive polymers for targeted intracellular anticancer drug delivery. Adv Funct Mater 17(3):355–362. doi:10.1002/adfm.200500611 CrossRefGoogle Scholar
  20. 20.
    Wang H, Zhao Y, Wu Y, Hu YL, Nan KH, Nie GJ, Chen H (2011) Enhanced anti-tumor efficacy by co-delivery of doxorubicin and paclitaxel with amphiphilic methoxy PEG-PLGA copolymer nanoparticles. Biomaterials 32(32):8281–8290. doi:10.1016/j.biomaterials.2011.07.032 CrossRefGoogle Scholar
  21. 21.
    Takahara PM, Rosenzweig AC, Frederick CA, Lippard SJ (1995) Crystal-structure of double-stranded DNA containing the major adduct of the anticancer drug cisplatin. Nature 377(6550):649–652. doi:10.1038/377649a0 CrossRefGoogle Scholar
  22. 22.
    Oerlemans C, Bult W, Bos M, Storm G, Nijsen JFW, Hennink WE (2010) Polymeric micelles in anticancer therapy: targeting, imaging and triggered release. Pharm Res 27(12):2569–2589. doi:10.1007/s11095-010-0233-4 CrossRefGoogle Scholar
  23. 23.
    Dinarvand R, Sepehri N, Manoochehri S, Rouhani H, Atyabi F (2011) Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents. Int J Nanomed 6:877–895. doi:10.2147/ijn.s18905 CrossRefGoogle Scholar
  24. 24.
    Vergaro V, Scarlino F, Bellomo C, Rinaldi R, Vergara D, Maffia M, Baldassarre F, Giannelli G, Zhang X, Lvov YM, Leporatti S (2011) Drug-loaded polyelectrolyte microcapsules for sustained targeting of cancer cells. Adv Drug Deliv Rev 63(9):847–864CrossRefGoogle Scholar
  25. 25.
    Peer D, Karp JM, Hong S, FaroKhzad OC, Margalit R, Langer R (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2(12):751–760. doi:10.1038/nnano.2007.387 CrossRefGoogle Scholar
  26. 26.
    Alexandrakis G, Brown EB, Tong RT, McKee TD, Campbell RB, Boucher Y, Jain RK (2004) Two-photon fluorescence correlation microscopy reveals the two-phase nature of transport in tumors. Nat Med 10(2):203–207. doi:10.1038/nm981 CrossRefGoogle Scholar
  27. 27.
    Geng Y, Dalhaimer P, Cai SS, Tsai R, Tewari M, Minko T, Discher DE (2007) Shape effects of filaments versus spherical particles in flow and drug delivery. Nat Nanotechnol 2(4):249–255. doi:10.1038/nnano.2007.70 CrossRefGoogle Scholar
  28. 28.
    Ramanujan S, Pluen A, McKee TD, Brown EB, Boucher Y, Jain RK (2002) Diffusion and convection in collagen gels: Implications for transport in the tumor interstitium. Biophys J 83(3):1650–1660CrossRefGoogle Scholar
  29. 29.
    Acharya S, Sahoo SK (2011) PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Adv Drug Deliv Rev 63(3):170–183. doi:10.1016/j.addr.2010.10.008 CrossRefGoogle Scholar
  30. 30.
    Alexis F, Rhee J-W, Richie JP, Radovic-Moreno AF, Langer R, Farokhzad OC (2008) New frontiers in nanotechnology for cancer treatment. Urol Oncol-Semin Ori Inv 26(1):74–85CrossRefGoogle Scholar
  31. 31.
    Bangham AD, Standish MM, Watkins JC (1965) Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 13(1):238, IN227CrossRefGoogle Scholar
  32. 32.
    Duncan R (2006) Polymer conjugates as anticancer nanomedicines. Nat Rev Cancer 6(9):688–701CrossRefGoogle Scholar
  33. 33.
    Haley B, Frenkel E (2008) Nanoparticles for drug delivery in cancer treatment. Urol Oncol-Semin Ori Inv 26(1):57–64. doi:10.1016/j.urolonc.2007.03.015 CrossRefGoogle Scholar
  34. 34.
    Thei DP, Eric Drexler JK et al (2006) Nanotechnology. Nat Nano 1(1):8–10CrossRefGoogle Scholar
  35. 35.
    Wang M, Thanou M (2010) Targeting nanoparticles to cancer. Pharmacol Res 62(2):90–99CrossRefGoogle Scholar
  36. 36.
    Sahoo SK, Parveen S, Panda JJ (2007) The present and future of nanotechnology in human health care. Nanomed-Nanotechnol Biol Med 3(1):20–31. doi:10.1016/j.nano.2006.11.008 CrossRefGoogle Scholar
  37. 37.
    Brannon-Peppas L, Blanchette JO (2004) Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev 56(11):1649–1659CrossRefGoogle Scholar
  38. 38.
    Davis ME, Chen Z, Shin DM (2008) Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov 7(9):771–782CrossRefGoogle Scholar
  39. 39.
    Jain RK, Stylianopoulos T (2010) Delivering nanomedicine to solid tumors. Nat Rev Clin Oncol 7(11):653–664. doi:10.1038/nrclinonc.2010.139 CrossRefGoogle Scholar
  40. 40.
    Zhuo C (2010) Small-molecule delivery by nanoparticles for anticancer therapy. Trends Mol Med 16(12):594–602CrossRefGoogle Scholar
  41. 41.
    Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65(1–2):271–284. doi:10.1016/s0168-3659(99)00248-5 CrossRefGoogle Scholar
  42. 42.
    Kloover JS, den Bakker MA, Gelderblom H, van Meerbeeck JP (2004) Fatal outcome of a hypersensitivity reaction to paclitaxel: a critical review of premedication regimens. Br J Cancer 90(2):304–305. doi:10.1038/sj.bjc.6601301 CrossRefGoogle Scholar
  43. 43.
    Farokhzad OC, Langer R (2009) Impact of nanotechnology on drug delivery. Acs Nano 3(1):16–20. doi:10.1021/nn900002m CrossRefGoogle Scholar
  44. 44.
    Ghosh K, Kanapathipillai M, Korin N, McCarthy JR, Ingber DE (2012) Polymeric nanomaterials for islet targeting and immunotherapeutic delivery. Nano Lett 12:203–208. doi:10.1021/nl203334c CrossRefGoogle Scholar
  45. 45.
    Parveen S, Misra R, Sahoo SK (2012) Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine 8:147–166Google Scholar
  46. 46.
    Prakash S, Malhotra M, Shao W, Tomaro-Duchesneau C, Abbasi S (2011) Polymeric nanohybrids and functionalized carbon nanotubes as drug delivery carriers for cancer therapy. Adv Drug Deliv Rev 63(14–15):1340–1351CrossRefGoogle Scholar
  47. 47.
    Janakiram NB, Rao CV (2008) Molecular markers and targets for colorectal cancer prevention. Acta Pharmacol Sin 29(1):1–20. doi:10.1111/j.1745-7254.2008.00742.x CrossRefGoogle Scholar
  48. 48.
    Mahmud A, Xiong XB, Aliabadi HM, Lavasanifar A (2007) Polymeric micelles for drug targeting. J Drug Target 15(9):553–584. doi:10.1080/10611860701538586 CrossRefGoogle Scholar
  49. 49.
    Ma WW, Adjei AA (2009) Novel agents on the horizon for cancer therapy. CA Cancer J Clin 59(2):111–137. doi:10.3322/caac.20003 CrossRefGoogle Scholar
  50. 50.
    Dhanikula AB, Panchagnula R (1999) Localized paclitaxel delivery. Int J Pharm 183(2):85–100. doi:10.1016/s0378-5173(99)00087-3 CrossRefGoogle Scholar
  51. 51.
    Bissell MJ, Radisky D (2001) Putting tumours in context. Nat Rev Cancer 1(1):46–54. doi:10.1038/35094059 CrossRefGoogle Scholar
  52. 52.
    Byrne JD, Betancourt T, Brannon-Peppas L (2008) Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev 60(15):1615–1626CrossRefGoogle Scholar
  53. 53.
    Ellis LM, Hicklin DJ (2008) VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer 8(8):579–591. doi:10.1038/nrc2403 CrossRefGoogle Scholar
  54. 54.
    Francavilla C, Maddaluno L, Cavallaro U (2009) The functional role of cell adhesion molecules in tumor angiogenesis. Semin Cancer Biol 19(5):298–309. doi:10.1016/j.semcancer.2009.05.004 CrossRefGoogle Scholar
  55. 55.
    Hynes RO (2002) A reevaluation of integrins as regulators of angiogenesis. Nat Med 8(9):918–921. doi:10.1038/nm0902-918 CrossRefGoogle Scholar
  56. 56.
    Kobayashi H, Boelte KC, Lin PC (2007) Endothelial cell adhesion molecules and cancer progression. Curr Med Chem 14(4):377–386. doi:10.2174/092986707779941032 CrossRefGoogle Scholar
  57. 57.
    Li LY, Wartchow CA, Danthi SN, Shen ZM, Dechene N, Pease J, Choi HS, Doede T, Chu P, Ning SC, Lee DY, Bednarski MD, Knox SJ (2004) A novel antiangiogenesis therapy using an integrin antagonist or anti-FLK-1 antibody coated Y-90-labeled nanoparticles. Int J Radiat Oncol Biol Phys 58(4):1215–1227. doi:10.1016/j.ijrob.2003.10.057 CrossRefGoogle Scholar
  58. 58.
    Zhao YS, Bachelier R, Treilleux I, Pujuguet P, Peyruchaud O, Baron R, Clement-Lacroix P, Clezardin P (2007) Tumor alpha(nu)beta(3) integrin is a therapeutic target for breast cancer bone metastases. Cancer Res 67(12):5821–5830. doi:10.1158/0008-5472.can-06-4499 CrossRefGoogle Scholar
  59. 59.
    Guarneri V, Dieci MV, Conte P (2012) Enhancing intracellular taxane delivery: current role and perspectives of nanoparticle albumin-bound paclitaxel in the treatment of advanced breast cancer. Expert Opin Pharmacother 13(3):395–406. doi:10.1517/14656566.2012.651127 CrossRefGoogle Scholar
  60. 60.
    Kim JG (2007) Cancer nanotechnology: engineering multifunctional nanostructures for targeting tumor cells and vasculatures. Georgia Institute of Technology, AtlantaGoogle Scholar
  61. 61.
    Daniels TR, Delgado T, Helguera G, Penichet ML (2006) The transferrin receptor. Part II: targeted delivery of therapeutic agents into cancer cells. Clin Immunol 121(2):159–176. doi:10.1016/j.clim.2006.06.006 CrossRefGoogle Scholar
  62. 62.
    Low PS, Antony AC (2004) Folate receptor-targeted drugs for cancer and inflammatory diseases—preface. Adv Drug Deliv Rev 56(8):1055–1058. doi:10.1016/j.addr.2004.02.003 CrossRefGoogle Scholar
  63. 63.
    Lu YJ, Low PS (2002) Folate targeting of haptens to cancer cell surfaces mediates immunotherapy of syngeneic murine tumors. Cancer Immunol Immunother 51(3):153–162. doi:10.1007/s00262-002-0266-6 CrossRefGoogle Scholar
  64. 64.
    Richardson DR, Kalinowski DS, Lau S, Jansson PJ, Lovejoy DB (2009) Cancer cell iron metabolism and the development of potent iron chelators as anti-tumour agents. Biochim Biophys Acta, Gen Subj 1790(7):702–717. doi:10.1016/j.bbagen.2008.04.003 CrossRefGoogle Scholar
  65. 65.
    Sridhar SS, Seymour L, Shepherd FA (2003) Inhibitors of epidermal-growth-factor receptors: a review of clinical research with a focus on non-small-cell lung cancer. Lancet Oncol 4(7):397–406. doi:10.1016/s1470-2045(03)01137-9 CrossRefGoogle Scholar
  66. 66.
    Jabr-Milane LS, van Vlerken LE, Yadav S, Amiji MM (2008) Multi-functional nanocarriers to overcome tumor drug resistance. Cancer Treat Rev 34(7):592–602. doi:10.1016/j.ctrv.2008.04.003 CrossRefGoogle Scholar
  67. 67.
    Kateb B, Chiu K, Black KL, Yamamoto V, Khalsa B, Ljubimova JY, Ding H, Patil R, Portilla-Arias JA, Modo M, Moore DF, Farahani K, Okun MS, Prakash N, Neman J, Ahdoot D, Grundfest W, Nikzad S, Heiss JD (2011) Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: what should be the policy? NeuroImage 54(1):S106–S124CrossRefGoogle Scholar
  68. 68.
    Shapira A, Livney YD, Broxterman HJ, Assaraf YG (2011) Nanomedicine for targeted cancer therapy: towards the overcoming of drug resistance. Drug Resist Updat 14(3):150–163CrossRefGoogle Scholar
  69. 69.
    Singh R, Lillard JW (2009) Nanoparticle-based targeted drug delivery. Exp Mol Pathol 86(3):215–223. doi:10.1016/j.yexmp.2008.12.004 CrossRefGoogle Scholar
  70. 70.
    Gong J, Chen M, Zheng Y, Wang S, Wang Y (2012) Polymeric micelles drug delivery system in oncology. J Control Release 159:312–323Google Scholar
  71. 71.
    Torchilin VP (2007) Micellar nanocarriers: pharmaceutical perspectives. Pharm Res 24(1):1–16. doi:10.1007/s11095-006-9132-0 CrossRefGoogle Scholar
  72. 72.
    van Vlerken LE, Vyas TK, Amiji MM (2007) Poly(ethylene glycol)-modified nanocarriers for tumor-targeted and intracellular delivery. Pharm Res 24(8):1405–1414. doi:10.1007/s11095-007-9284-6 CrossRefGoogle Scholar
  73. 73.
    Chan JM, Zhang LF, Yuet KP, Liao G, Rhee JW, Langer R, Farokhzad OC (2009) PLGA-lecithin-PEG core-shell nanoparticles for controlled drug delivery. Biomaterials 30(8):1627–1634. doi:10.1016/j.biomaterials.2008.12.013 CrossRefGoogle Scholar
  74. 74.
    Mansour HM, Sohn M, Al-Ghananeem A, DeLuca PP (2010) Materials for pharmaceutical dosage forms: molecular pharmaceutics and controlled release drug delivery aspects. Int J Mol Sci 11(9):3298–3322. doi:10.3390/ijms11093298 CrossRefGoogle Scholar
  75. 75.
    Mohamed F, van der Walle CF (2008) Engineering biodegradable polyester particles with specific drug targeting and drug release properties. J Pharm Sci 97(1):71–87. doi:10.1002/jps.21082 CrossRefGoogle Scholar
  76. 76.
    Yang L, Zhang LJ, Webster TJ (2011) Nanobiomaterials: state of the art and future trends. Adv Eng Mater 13(6):B197–B217. doi:10.1002/adem.201080140 CrossRefGoogle Scholar
  77. 77.
    Bajpai AK, Shukla SK, Bhanu S, Kankane S (2008) Responsive polymers in controlled drug delivery. Prog Polym Sci 33(11):1088–1118. doi:10.1016/j.progpolymsci.2008.07.005 CrossRefGoogle Scholar
  78. 78.
    Seyednejad H, Ghassemi AH, van Nostrum CF, Vermonden T, Hennink WE (2011) Functional aliphatic polyesters for biomedical and pharmaceutical applications. J Control Release 152(1):168–176. doi:10.1016/j.jconrel.2010.12.016 CrossRefGoogle Scholar
  79. 79.
    Vroman I, Tighzert L (2009) Biodegradable polymers. Materials 2(2):307–344. doi:10.3390/ma2020307 CrossRefGoogle Scholar
  80. 80.
    Park J, Mattessich T, Jay SM, Agawu A, Saltzman WM, Fahmy TM (2011) Enhancement of surface ligand display on PLGA nanoparticles with amphiphilic ligand conjugates. J Control Release 156(1):109–115CrossRefGoogle Scholar
  81. 81.
    Gaucher GV, Marchessault RH, Leroux J-C (2010) Polyester-based micelles and nanoparticles for the parenteral delivery of taxanes. J Control Release 143(1):2–12CrossRefGoogle Scholar
  82. 82.
    Kumari A, Yadav SK, Yadav SC (2010) Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B-Biointerfaces 75(1):1–18. doi:10.1016/j.colsurfb.2009.09.001 CrossRefGoogle Scholar
  83. 83.
    Liong M, Lu J, Kovochich M, Xia T, Ruehm SG, Nel AE, Tamanoi F, Zink JI (2008) Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery. Acs Nano 2(5):889–896. doi:10.1021/nn800072t CrossRefGoogle Scholar
  84. 84.
    Park JH, Lee S, Kim JH, Park K, Kim K, Kwon IC (2008) Polymeric nanomedicine for cancer therapy. Prog Polym Sci 33(1):113–137. doi:10.1016/j.progpolymsci.2007.09.003 CrossRefGoogle Scholar
  85. 85.
    Schroeder A, Heller DA, Winslow MM, Dahlman JE, Pratt GW, Langer R, Jacks T, Anderson DG (2012) Treating metastatic cancer with nanotechnology. Nat Rev Cancer 12(1):39–50CrossRefGoogle Scholar
  86. 86.
    Zhou Q, Guo X, Chen T, Zhang Z, Shao SJ, Luo C, Li JR, Zhou SB (2011) Target-specific cellular uptake of folate-decorated biodegradable polymer micelles. J Phys Chem B 115(43):12662–12670. doi:10.1021/jp207951e CrossRefGoogle Scholar
  87. 87.
    Danquah MK, Zhang XA, Mahato RI (2011) Extravasation of polymeric nanomedicines across tumor vasculature. Adv Drug Deliv Rev 63(8):623–639CrossRefGoogle Scholar
  88. 88.
    Jang SH, Wientjes MG, Lu D, Au JLS (2003) Drug delivery and transport to solid tumors. Pharm Res 20(9):1337–1350. doi:10.1023/a:1025785505977 CrossRefGoogle Scholar
  89. 89.
    Liang CY, Yang YB, Ling Y, Huang YS, Li T, Li XM (2011) Improved therapeutic effect of folate-decorated PLGA-PEG nanoparticles for endometrial carcinoma. Bioorg Med Chem 19(13):4057–4066. doi:10.1016/j.bmc.2011.05.016 CrossRefGoogle Scholar
  90. 90.
    Maeda H, Bharate GY, Daruwalla J (2009) Polymeric drugs for efficient tumor-targeted drug delivery based on EPR-effect. Eur J Pharm Biopharm 71(3):409–419. doi:10.1016/j.ejpb.2008.11.010 CrossRefGoogle Scholar
  91. 91.
    Maeda H, Greish K, Fang J (2006) The EPR effect and polymeric drugs: a paradigm shift for cancer chemotherapy in the 21st century. In: SatchiFainaro R, Duncan R (eds) Polymer therapeutics II: Polymers as drugs, conjugates and gene delivery systems. Adv Polym Sci 193:103–121. doi:10.1007/12_026
  92. 92.
    Xu J, Ganesh S, Amiji M (2011) Non-condensing polymeric nanoparticles for targeted gene and siRNA delivery. Int J Pharm 427:21–34Google Scholar
  93. 93.
    Bae YH, Park K (2011) Targeted drug delivery to tumors: myths, reality and possibility. J Control Release 153(3):198–205CrossRefGoogle Scholar
  94. 94.
    Couvreur P, Vauthier C (2006) Nanotechnology: intelligent design to treat complex disease. Pharm Res 23(7):1417–1450. doi:10.1007/s11095-006-0284-8 CrossRefGoogle Scholar
  95. 95.
    Danhier F, Feron O, Preat V (2010) To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release 148(2):135–146. doi:10.1016/j.jconrel.2010.08.027 CrossRefGoogle Scholar
  96. 96.
    Lammers T, Kiessling F, Hennink WE, Storm G (2012) Drug targeting to tumors: Principles, pitfalls and (pre-) clinical progress. J Control Release 161:175–187Google Scholar
  97. 97.
    Lee ES, Gao ZG, Bae YH (2008) Recent progress in tumor pH targeting nanotechnology. J Control Release 132(3):164–170. doi:10.1016/j.jconrel.2008.05.003 CrossRefGoogle Scholar
  98. 98.
    Vladimir T (2009) Multifunctional and stimuli-sensitive pharmaceutical nanocarriers. Eur J Pharm Biopharm 71(3):431–444CrossRefGoogle Scholar
  99. 99.
    Caldorera-Moore ME, Liechty WB, Peppas NA (2011) Responsive theranostic systems: integration of diagnostic imaging agents and responsive controlled release drug delivery carriers. Acc Chem Res 44(10):1061–1070. doi:10.1021/ar2001777 CrossRefGoogle Scholar
  100. 100.
    Mahato R, Tai WY, Cheng K (2011) Prodrugs for improving tumor targetability and efficiency. Adv Drug Deliv Rev 63(8):659–670. doi:10.1016/j.addr.2011.02.002 CrossRefGoogle Scholar
  101. 101.
    El-Aneed A (2004) An overview of current delivery systems in cancer gene therapy. J Control Release 94(1):1–14. doi:10.1016/j.jconrel.2003.09.013 CrossRefGoogle Scholar
  102. 102.
    Guo P, Coban O, Snead NM, Trebley J, Hoeprich S, Guo S, Shu Y (2010) Engineering RNA for Targeted siRNA delivery and medical application. Adv Drug Deliv Rev 62(6):650–666CrossRefGoogle Scholar
  103. 103.
    Hu C-MJ, Zhang L (2012) Nanoparticle-based combination therapy toward overcoming drug resistance in cancer. Biochem Pharmacol 83(8):1104–1111CrossRefGoogle Scholar
  104. 104.
    Patil Y, Panyam J (2009) Polymeric nanoparticles for siRNA delivery and gene silencing. Int J Pharm 367(1–2):195–203. doi:10.1016/j.ijpharm.2008.09.039 CrossRefGoogle Scholar
  105. 105.
    Cheng J, Teply BA, Sherifi I, Sung J, Luther G, Gu FX, Levy-Nissenbaum E, Radovic-Moreno AF, Langer R, Farokhzad OC (2007) Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery. Biomaterials 28(5):869–876. doi:10.1016/j.biomaterials.2006.09.047 CrossRefGoogle Scholar
  106. 106.
    Kocbek P, Obermajer N, Cegnar M, Kos J, Kristl J (2007) Targeting cancer cells using PLGA nanoparticles surface modified with monoclonal antibody. J Control Release 120(1–2):18–26. doi:10.1016/j.jconrel.2007.03.012 CrossRefGoogle Scholar
  107. 107.
    Liu Y, Li K, Pan J, Liu B, Feng S-S (2010) Folic acid conjugated nanoparticles of mixed lipid monolayer shell and biodegradable polymer core for targeted delivery of Docetaxel. Biomaterials 31(2):330–338CrossRefGoogle Scholar
  108. 108.
    Park J, Fong PM, Lu J, Russell KS, Booth CJ, Saltzman WM, Fahmy TM (2009) PEGylated PLGA nanoparticles for the improved delivery of doxorubicin. Nanomed-Nanotechnol Biol Med 5(4):410–418. doi:10.1016/j.nano.2009.02.002 CrossRefGoogle Scholar
  109. 109.
    Sutton D, Nasongkla N, Blanco E, Gao JM (2007) Functionalized micellar systems for cancer targeted drug delivery. Pharm Res 24(6):1029–1046. doi:10.1007/s11095-006-9223-y CrossRefGoogle Scholar
  110. 110.
    Zhou J, Patel TR, Fu M, Bertram JP, Saltzman WM (2012) Octa-functional PLGA nanoparticles for targeted and efficient siRNA delivery to tumors. Biomaterials 33(2):583–591CrossRefGoogle Scholar
  111. 111.
    Efthimiadou EK, Tapeinos C, Bilalis P, Kordas G (2011) New approach in synthesis, characterization and release study of pH-sensitive polymeric micelles, based on PLA-Lys-b-PEGm, conjugated with doxorubicin. J Nanoparticle Res 13(12):6725–6736. doi:10.1007/s11051-011-0579-5 CrossRefGoogle Scholar
  112. 112.
    Yoo J-W, Doshi N, Mitragotri S (2011) Adaptive micro and nanoparticles: temporal control over carrier properties to facilitate drug delivery. Adv Drug Deliv Rev 63(14–15):1247–1256CrossRefGoogle Scholar
  113. 113.
    Rasal RM, Janorkar AV, Hirt DE (2010) Poly(lactic acid) modifications. Prog Polym Sci 35(3):338–356. doi:10.1016/j.progpolymsci.2009.12.003 CrossRefGoogle Scholar
  114. 114.
    Thamake SI, Raut SL, Ranjan AP, Gryczynski Z, Vishwanatha JK (2011) Surface functionalization of PLGA nanoparticles by non-covalent insertion of a homo-bifunctional spacer for active targeting in cancer therapy. Nanotechnology 22(3):035101. doi:10.1088/0957-4484/22/3/035101 CrossRefGoogle Scholar
  115. 115.
    Sussman EM, Clarke MB, Shastri VP (2007) Single-step process to produce surface-functionalized polymeric nanoparticles. Langmuir 23(24):12275–12279. doi:10.1021/la701997x CrossRefGoogle Scholar
  116. 116.
    Wiradharma N, Zhang Y, Venkataraman S, Hedrick JL, Yang YY (2009) Self-assembled polymer nanostructures for delivery of anticancer therapeutics. Nano Today 4(4):302–317. doi:10.1016/j.nantod.2009.06.001 CrossRefGoogle Scholar
  117. 117.
    Chung YI, Kim JC, Kim YH, Tae G, Lee SY, Kim K, Kwon IC (2010) The effect of surface functionalization of PLGA nanoparticles by heparin- or chitosan-conjugated Pluronic on tumor targeting. J Control Release 143(3):374–382. doi:10.1016/j.jconrel.2010.01.017 CrossRefGoogle Scholar
  118. 118.
    Parveen S, Sahoo SK (2011) Long circulating chitosan/PEG blended PLGA nanoparticle for tumor drug delivery. Eur J Pharmacol 670(2–3):372–383CrossRefGoogle Scholar
  119. 119.
    Bilensoy E, Sarisozen C, Esendagli G, Dogan AL, Aktas Y, Sen M, Mungan NA (2009) Intravesical cationic nanoparticles of chitosan and polycaprolactone for the delivery of Mitomycin C to bladder tumors. Int J Pharm 371(1–2):170–176. doi:10.1016/j.ijpharm.2008.12.015 CrossRefGoogle Scholar
  120. 120.
    Chakravarthi SS, Robinson DH (2011) Enhanced cellular association of paclitaxel delivered in chitosan-PLGA particles. Int J Pharm 409(1–2):111–120. doi:10.1016/j.ijpharm.2011.02.034 CrossRefGoogle Scholar
  121. 121.
    Khandare J, Minko T (2006) Polymer–drug conjugates: progress in polymeric prodrugs. Prog Polym Sci 31(4):359–397CrossRefGoogle Scholar
  122. 122.
    Thanh NTK, Green LAW (2010) Functionalisation of nanoparticles for biomedical applications. Nano Today 5(3):213–230. doi:10.1016/j.nantod.2010.05.003 CrossRefGoogle Scholar
  123. 123.
    Dhar S, Gu FX, Langer R, Farokhzad OC, Lippard SJ (2008) Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA-PEG nanoparticles. Proc Natl Acad Sci U S A 105(45):17356–17361. doi:10.1073/pnas.0809154105 CrossRefGoogle Scholar
  124. 124.
    Zhao H, Yung LYL (2008) Selectivity of folate conjugated polymer micelles against different tumor cells. Int J Pharm 349(1–2):256–268CrossRefGoogle Scholar
  125. 125.
    Pan J, Feng SS (2008) Targeted delivery of paclitaxel using folate-decorated poly(lactide)—vitamin E TPGS nanoparticles. Biomaterials 29(17):2663–2672. doi:10.1016/j.biomaterials.2008.02.020 CrossRefGoogle Scholar
  126. 126.
    Wang C, Ho PC, Lim LY (2010) Wheat germ agglutinin-conjugated PLGA nanoparticles for enhanced intracellular delivery of paclitaxel to colon cancer cells. Int J Pharm 400(1–2):201–210CrossRefGoogle Scholar
  127. 127.
    Heidel JD, Davis ME (2011) Clinical developments in nanotechnology for cancer therapy. Pharm Res 28(2):187–199. doi:10.1007/s11095-010-0178-7 CrossRefGoogle Scholar
  128. 128.
    Lee SH, Mok H, Lee Y, Park TG (2011) Self-assembled siRNA-PLGA conjugate micelles for gene silencing. J Control Release 152(1):152–158. doi:10.1016/j.jconrel.2010.12.007 CrossRefGoogle Scholar
  129. 129.
    Susa M, Milane L, Amiji MM, Hornicek FJ, Duan ZF (2011) Nanoparticles: a promising modality in the treatment of sarcomas. Pharm Res 28(2):260–272. doi:10.1007/s11095-010-0173-z CrossRefGoogle Scholar
  130. 130.
    Hans ML, Lowman AM (2002) Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater Sci 6(4):319–327. doi:10.1016/s1359-0286(02)00117-1 CrossRefGoogle Scholar
  131. 131.
    Xiong XB, Uludag H, Lavasanifar A (2009) Biodegradable amphiphilic poly(ethylene oxide)-block-polyesters with grafted polyamines as supramolecular nanocarriers for efficient siRNA delivery. Biomaterials 30(2):242–253. doi:10.1016/j.biomaterials.2008.09.025 CrossRefGoogle Scholar
  132. 132.
    Bastani B, Fernandez D (2002) Intellectual property rights in nanotechnology. Thin Solid Films 420:472–477. doi:10.1016/s0040-6090(02)00843-x CrossRefGoogle Scholar
  133. 133.
    Merchant M (2010) Nanotechnology in Healthcare. Business Insights, 16–218Google Scholar
  134. 134.
    Koppikar V, Maebius S, Rutt S (2004) Current trends in nanotech patents: a view from inside the patent office. Nanotechnol Law Bus 1(1):24–30Google Scholar
  135. 135.
    Laurie A, Axford GRL (2006) Patent drafting considerations for nanotechnology inventions. Nanotechnol Law Bus 3(3):305Google Scholar
  136. 136.
    O’Neill S, Hermann K, Klein M, Landes J, Bawa R (2007) Broad claiming in nanotechnology patents: is litigation inevitable? Nanotechnol Law Bus 4(1):595–606Google Scholar
  137. 137.
    Fraser-Moodie I (2008) Delivery mechanisms for large molecule drugs. Business Insights, 10–138Google Scholar
  138. 138.
    EPO (2010) Guidelines for examination in the European Patent Office. Part C—guidelines for substantive examination—Chapter IV patentability.Google Scholar
  139. 139.
    Burgess P, Hutt PB, Farokhzad OC, Langer R, Minick S, Zale S (2010) On firm ground: IP protection of therapeutic nanoparticles. Nat Biotechnol 28(12):1267–1271. doi:10.1038/nbt.1725 CrossRefGoogle Scholar
  140. 140.
    Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335–2342. doi:10.1056/NEJMoa032691 CrossRefGoogle Scholar
  141. 141.
    Shepherd FA, Pereira JR, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu DS, Johnston D, Bezjak A, Clark G, Santabarbara P, Seymour L, Natl Canc Inst Canada Clin T (2005) Erlotinib in previously treated non-small-cell lung cancer. New Eng J Med 353(2):123–132. doi:10.1056/NEJMoa050753 CrossRefGoogle Scholar
  142. 142.
    Kuesters GM, Campbell RB (2010) Conjugation of bevacizumab to cationic liposomes enhances their tumor-targeting potential. Nanomedicine 5(2):181–192. doi:10.2217/nnm.09.105 CrossRefGoogle Scholar
  143. 143.
    Shorr R, Rodriguez R (2007) Pharmaceutical and diagnostic compositions containing nanoparticles useful for treating targeted tissues and cells. US patent no. 7,521,066Google Scholar
  144. 144.
    Borbely J, Bodnar M, Hartmann JF, Hajdu I, Kollar J, Vamosi G (2008) Cancer cell diagnosis by targeting delivery of nanodevices. US patent no. 7,976,825Google Scholar
  145. 145.
    Huff TB, Tong L, Zhao Y, Hansen MN, Cheng JX, Wei A (2007) Hyperthermic effects of gold nanorods on tumor cells. Nanomedicine 2(1):125–132. doi:10.2217/17435889.2.1.125 CrossRefGoogle Scholar
  146. 146.
    Dixit V, Van den Bossche J, Sherman DM, Thompson DH, Andres RP (2006) Synthesis and grafting of thioctic acid-PEG-folate conjugates onto Au nanoparticles for selective targeting of folate receptor-positive tumor cells. Bioconjug Chem 17(3):603–609. doi:10.1021/bc050335b CrossRefGoogle Scholar
  147. 147.
    El-Sayed IH, Huang XH, El-Sayed MA (2006) Selective laser photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles. Cancer Lett 239(1):129–135. doi:10.1016/j.canlet.2005.07.035 CrossRefGoogle Scholar
  148. 148.
    Cleator S, Heller W, Coombes RC (2007) Triple-negative breast cancer: therapeutic options. Lancet Oncol 8(3):235–244. doi:10.1016/s1470-2045(07)70074-8 CrossRefGoogle Scholar
  149. 149.
    Oyelere Adegboyega K, EL-Sayed Mostafa A, Dreaden EC (2009) Targeted cellular delivery of nanoparticles. US Patent application no. 2011077581Google Scholar
  150. 150.
    Akhtari M, Engel J (2009) Use of functionalized magnetic nanoparticles in cancer detection and treatment. US Patent application no. 2011044911Google Scholar
  151. 151.
    Layton B (2008) Recent patents in bionanotechnologies: nanolithography, bionanocomposites, cell-based computing and entropy production. US patent no. 7,638,558Google Scholar
  152. 152.
    Liu L, Li C, Li X, Yuan Z, An Y, He B (2001) Biodegradable polylactide/poly(ethylene glycol)/polylactide triblock copolymer micelles as anticancer drug carriers. J Appl Polym Sci 80(11):1976–1982. doi:10.1002/app.1295 CrossRefGoogle Scholar
  153. 153.
    Radosz M, Xu P, Shen Y (2005) Nanoparticles for cytoplasmic drug delivery to cancer cells. US Patent application no. 2010203149Google Scholar
  154. 154.
    Desai NP, Soon-Shiong P (2007) Breast cancer therapy based on hormone receptor status with nanoparticles comprising taxane. US Patent application no. 20070519126Google Scholar
  155. 155.
    Moradi M (2005) Global developments in nano-enabled drug delivery market. Nanothecnology Law & Business 2(2):139–148Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Michele F. Oliveira
    • 1
  • Pedro P. G. Guimarães
    • 1
  • Alinne D. M. Gomes
    • 1
  • Diego Suárez
    • 1
  • Rubén D. Sinisterra
    • 1
  1. 1.Departamento de Química, Instituto de Ciências ExatasUniversidade Federal de Minas Gerais (UFMG)Belo HorizonteBrazil

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