Abstract
Among the many scientific advances to come from the study of nanoscience, the development of ligand-targeted nanoparticles to eliminate solid tumors is predicted to have a major impact on human health. There are many reports describing novel designs and testing of targeted nanoparticles to treat cancer. While the principles of the technology are well demonstrated in controlled lab experiments, there are still many hurdles to overcome for the science to mature into truly efficacious targeted nanoparticles that join the arsenal of agents currently used to treat cancer in humans. One of these hurdles is overcoming unwanted biodistribution to the liver while maximizing delivery to the tumor. This almost certainly requires advances in both nanoparticle stealth technology and targeting. Currently, it continues to be a challenge to control the loading of ligands onto polyethylene glycol (PEG) to achieve maximal targeting. Nanoparticle cellular uptake and subcellular targeting of genes and siRNA also remain a challenge. This review examines the types of ligands that have been most often used to target nanoparticles to solid tumors. As the science matures over the coming decade, careful control over ligand presentation on nanoparticles of precise size, shape, and charge will likely play a major role in achieving success.
Similar content being viewed by others
References
Wisse E, De Zanger RB, Charels K, Van Der Smissen P, McCuskey RS. The liver sieve: considerations concerning the structure and function of endothelial fenestrae, the sinusoidal wall and the space of Disse. Hepatology. 1985;5(4):683–92.
Torchilin VP. Targeted pharmaceutical nanocarriers for cancer therapy and imaging. AAPS J. 2007;9(2):E128–47.
Rettig GR, Rice KG. Non-viral gene delivery: from the needle to the nucleus. Expert Opin Biol Ther. 2007;7(6):799–808.
Das M, Mohanty C, Sahoo SK. Ligand-based targeted therapy for cancer tissue. Expert Opin Drug Deliv. 2009;6(3):285–304.
Iyer AK, Khaled G, Fang J, Maeda H. Exploiting the enhanced permeability and retention effect for tumor targeting. Drug Discov Today. 2006;11(17–18):812–8.
Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer-chemotherapy—mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 1986;46(12):6387–92.
Fleischer CC, Payne CK. Nanoparticle surface charge mediates the cellular receptors used by protein-nanoparticle complexes. J Phys Chem B. 2012;116(30):8901–7.
Liu Z, Jiao Y, Wang T, Zhang Y, Xue W. Interactions between solubilized polymer molecules and blood components. J Cont Rel. 2012;160(1):14–24.
Merdan T, Kunath K, Petersen H, Bakowsky U, Voigt KH, Kopecek J, et al. PEGylation of poly(ethylene imine) affects stability of complexes with plasmid DNA under in vivo conditions in a dose-dependent manner after intravenous injection into mice. Bioconj Chem. 2005;16(4):785–92.
Yan X, Kuipers F, Havekes LM, Havinga R, Dontje B, Poelstra K, et al. The role of apolipoprotein E in the elimination of liposomes from blood by hepatocytes in the mouse. Bioch Biophys Res Commun. 2005;328(1):57–62.
Jansen RW, Molema G, Harms G, Kruijt JK, van Berkel TJC, Hardonk MJ, et al. Formaldehyde treated albumin contains monomeric and polymeric forms that are differently cleared by endothelial and kupffer cells of the liver: evidence for scavenger receptor heterogeneity. Biochem Biophys Res Commun. 1991;180:23–32.
Kawabata K, Takakura Y, Hashida M. The fate of plasmid DNA after intravenous injection in mice: involvement of scavenger receptors in its hepatic uptake. Pharm Res. 1995;12(6):825–30.
Kamps JA, Morselt HW, Swart PJ, Meijer DK, Scherphof GL. Massive targeting of liposomes, surface-modified with anionized albumins, to hepatic endothelial cells. Proc Natl Acad Sci U S A. 1997;94(21):11681–5.
Xu Z, Tian J, Smith JS, Byrnes AP. Clearance of adenovirus by Kupffer cells is mediated by scavenger receptors, natural antibodies, and complement. J Virol. 2008;82(23):11705–13.
Kamps JA, Scherphof GL. Receptor versus non-receptor mediated clearance of liposomes. Adv Drug Del Rev. 1998;32(1–2):81–97.
Wong SY, Pelet JM, Putnam D. Polymer systems for gene delivery-past, present, and future. Prog Polym Sci. 2007;32(8–9):799–837.
Tseng Y-C, Mozumdar S, Huang L. Lipid-based systemic delivery of siRNA. Adv Drug Deliv Rev. 2009;61(9):721–31.
Martin ME, Rice KG. Peptide-guided gene delivery. AAPS J. 2007;9(1):E18–29.
Hatakeyama H, Akita H, Harashima H. A multifunctional envelope type nano device (MEND) for gene delivery to tumours based on the EPR effect: a strategy for overcoming the PEG dilemma. Adv Drug Deliv Rev. 2011;63(3):152–60.
Lozza C, Navarro-Teulon I, Pelegrin A, Pouget J-P, Vives E. Peptides in receptor-mediated radiotherapy: from design to the clinical application in cancers. Front Oncol. 2013;3(247):1–13.
Kizzire K, Khargharia S, Rice KG. High-affinity PEGylated polyacridine peptide polyplexes mediate potent in vivo gene expression. Gene Ther. 2013;20(4):407–16.
Oupicky D, Konak C, Dash PR, Seymour LW, Ulbrich K. Effect of albumin and polyanion on the structure of DNA complexes with polycation containing hydrophilic nonionic block. Bioconjug Chem. 1999;10(5):764–72.
Dash PR, Read ML, Barrett LB, Wolfert MA, Seymour LW. Factors affecting blood clearance and in vivo distribution of polyelectrolyte complexes for gene delivery. Gene Ther. 1999;6:643–50.
Khargharia S, Kizzire K, Ericson MD, Baumhover NJ, Rice KG. PEG length and chemical linkage controls polyacridine peptide DNA polyplex pharmacokinetics, biodistribution, metabolic stability and in vivo gene expression. J Cont Rel. 2013;170(3):325–33.
Khargharia S, Baumhover NJ, Duskey JT, Crowley ST, Rice KG. Mechanism of PEGyalted DNA polyplex capture by the liver. Molecular therapy. 2014:submitted.
Nobs L, Buchegger F, Gurny R, Allemann E. Current methods for attaching targeting ligands to liposomes and nanoparticles. J Pharm Sci. 2004;93(8):1980–92.
Liu YP, Tong C, Dispenzieri A, Federspiel MJ, Russell SJ, Peng KW. Polyinosinic acid decreases sequestration and improves systemic therapy of measles virus. Cancer Gene Ther. 2012;19(3):202–11.
Burkel WE, Low FN. The fine structure of rat liver sinusoids, space of Disse and associated tissue space. Amer J Anat. 1966;118(3):769–83.
Scherphof GL, Kamps JA. The role of hepatocytes in the clearance of liposomes from the blood circulation. Prog Lipid Res. 2001;40(3):149–66.
Kamps JA, Scherphof GL. Biodistribution and uptake of liposomes in vivo. Methods Enzym. 2004;387:257–66.
Li SD, Huang L. Nanoparticles evading the reticuloendothelial system: role of the supported bilayer. Biochim Biophys Acta. 2009;1788(10):2259–66.
Varkouhi AK, Scholte M, Storm G, Haisma HJ. Endosomal escape pathways for delivery of biologicals. J Cont Rel. 2011;151(3):220–8.
Giacca M, Zacchigna S. Virus-mediated gene delivery for human gene therapy. J Cont Rel. 2012;161(2):377–88.
Paszko E, Senge MO. Immunoliposomes. Curr Med Chem. 2012;19(31):5239–77.
Josan JS, Handl HL, Sankaranarayanan R, Xu L, Lynch RM, Vagner J, et al. Cell-specific targeting by heterobivalent ligands. Bioconjug Chem. 2011;22(7):1270–8.
Munoz EM, Correa J, Riguera R, Fernandez-Megia E. Real-time evaluation of binding mechanisms in multivalent interactions: a surface plasmon resonance kinetic approach. JACS.135(16):5966–5969.
Cecioni S, Faure S, Darbost U, Bonnamour I, Parrot-Lopez H, Roy O, et al. Selectivity among two lectins: probing the effect of topology, multivalency and flexibility of “clicked” multivalent glycoclusters. Chem-a Eur J. 17(7):2146–2159.
Lundquist JJ, Toone EJ. The cluster glycoside effect. Chem Rev. 2002;102(2):555–78.
Kane RS. Thermodynamics of multivalent interactions: influence of the linker. Langmuir. 2010;26(11):8636–40.
Mammen M, Choi SK, Whitesides GM. Polyvalent interactions in biological systems: implications for design and use of multivalent ligands and inhibitors. Angew Chem-Int Ed. 1998;37(20):2755–94.
Ashley CE, Carnes EC, Phillips GK, Padilla D, Durfee PN, Brown PA, et al. The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers (vol 10, pg 389, 2011). Nat Mater. 2011;10(5):389–397. doi:10.1038/nmat2992.
Zarbock A, Ley K, McEver RP, Hidalgo A. Leukocyte ligands for endothelial selectins: specialized glycoconjugates that mediate rolling and signaling under flow. Blood. 2011;118(26):6743–51.
Pirollo KF, Chang EH. Does a targeting ligand influence nanoparticle tumor localization or uptake? Trends Biotechnol. 2008;26(10):552–8.
Bartlett DW, Su H, Hildebrandt IJ, Weber WA, Davis ME. Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging. Proc Natl Acad Sci U S A. 2007;104(39):15549–54.
Wu AM, Yazaki PJ, Tsai SW, Nguyen K, Anderson AL, McCarthy DW, et al. High-resolution microPET imaging of carcino-embryonic antigen-positive xenografts by using a copper-64-labeled engineered antibody fragment. Proc Natl Acad Sci U S A. 2000;97(15):8495–500.
Hussain S, Plueckthun A, Allen TM, Zangemeister-Wittke U. Antitumor activity of an epithelial cell adhesion molecule-targeted nanovesicular drug delivery system. Mol Cancer Ther. 2007;6(11):3019–27.
Kirpotin DB, Drummond DC, Shao Y, Shalaby MR, Hong K, Nielsen UB, et al. Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models. Cancer Res. 2006;66(13):6732–40.
Neves MAD, Reinstein O, Saad M, Johnson PE. Defining the secondary structural requirements of a cocaine-binding aptamer by a thermodynamic and mutation study. Biophys Chem. 2010;153(1):9–16.
Song K-M, Lee S, Ban C. Aptamers and their biological applications. Sensors. 2012;12(1):612–31.
Cho EJ, Lee J-W, Ellington AD. Applications of aptamers as sensors. Annu Rev Anal Chem. 2009;2:241–64.
Wang H-Q, Wu Z, Tang L-J, Yu R-Q, Jiang J-H. Fluorescence protection assay: a novel homogeneous assay platform toward development of aptamer sensors for protein detection. Nucleic Acids Research. 2011;39(18).
Cerchia L, de Franciscis V. Nucleic acid-based aptamers as promising therapeutics in neoplastic diseases. Methods Mol Biol. 2007;361:187–200.
Mongelard F, Bouvet P. AS-1411, a guanosine-rich oligonucleotide aptamer targeting nucleolin for the potential treatment of cancer, including acute myeloid leukemia. Curr Opin Mol Ther. 2010;12(1):107–14.
Wilner SE, Wengerter B, Maier K, de Lourdes Borba Magalhaes M, Del Amo DS, Pai S, et al. An RNA alternative to human transferrin: a new tool for targeting human cells. Mol Ther Nucleic Acids. 2012;1:e21–1.
Thiel KW, Hernandez LI, Dassie JP, Thiel WH, Liu X, Stockdale KR, et al. Delivery of chemo-sensitizing siRNAs to HER2(+)-breast cancer cells using RNA aptamers. Nucleic Acids Res. 2012;40(13):6319–37.
Gupta S, Thirstrup D, Jarvis TC, Schneider DJ, Wilcox SK, Carter J, et al. Rapid histochemistry using slow off-rate modified aptamers with anionic competition. Appl Immunohistochem Mol Morphol. 2011;19(3):273–8.
Cerchia L, Esposito CL, Camorani S, Rienzo A, Stasio L, Insabato L, et al. Targeting axl with an high-affinity inhibitory aptamer. Mol Ther. 2012;20(12):2291–303.
Nishimoto T, Yamamoto Y, Yoshida K, Goto N, Ohnami S, Aoki K. Development of peritoneal tumor-targeting vector by in vivo screening with a random peptidedisplaying adenovirus library. Plos One. 2012;7(9):e45550–5.
Kurosaki T, Higuchi N, Kawakami S, Higuchi Y, Nakamura T, Kitahara T, et al. Self-assemble gene delivery system for molecular targeting using nucleic acid aptamer. Gene. 2012;491(2):205–9.
Daniels TR, Bernabeu E, Rodriguez JA, Patel S, Kozman M, Chiappetta DA, et al. The transferrin receptor and the targeted delivery of therapeutic agents against cancer. Biochim Et Biophys Acta-Gen Subj. 2012;1820(3):291–317.
Hogemann D, Josephson L, Weissleder R, Basilion JP. Improvement of MRI probes to allow efficient detection of gene expression. Bioconjug Chem. 2000;11(6):941–6.
Hogemann-Savellano D, Bos E, Blondet C, Sato F, Abe T, Josephson L, et al. The transferrin receptor: a potential molecular Imaging marker for human cancer. Neoplasia. 2003;5(6):495–506.
Davis ME. The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinic. Mol Pharm. 2009;6(3):659–68.
Senzer N, Nemunaitis J, Nemunaitis D, Bedell C, Edelman G, Barve M, et al. Phase I study of a systemically delivered p53 nanoparticle in advanced solid tumors. Mol Ther. 2013;21(5):1096–103.
Khalaj-Kondori M, Sadeghizadeh M, Behmanesh M, Saggio I, Monaci P. Chemical coupling as a potent strategy for preparation of targeted bacteriophage-derived gene nanocarriers into eukaryotic cells. J Gene Med. 2011;13(11):622–31.
Hilgenbrink AR, Low PS. Folate receptor-mediated drug targeting: from therapeutics to diagnostics. J Pharm Sci. 2005;94(10):2135–46.
Yang J, Vlashi E, Low P. Folate-linked drugs for the treatment of cancer and inflammatory diseases. Sub-Cell Biochem. 2012;56:163–79.
Muller C, Schibli R. Prospects in folate receptor-targeted radionuclide therapy. Front Oncol. 2013;3:249.
Shiokawa T, Hattori Y, Kawano K, Ohguchi Y, Kawakami H, Toma K, et al. Effect of polyethylene glycol linker chain length of folate-linked microemulsions loading aclacinomycin a on targeting ability and antitumor effect in vitro and in vivo. Clin Cancer Res. 2005;11(5):2018–25.
Lee H, Lytton-Jean AKR, Chen Y, Love KT, Park AI, Karagiannis ED, et al. Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery. Nat Nanotechnol. 2012;7(6):389–93.
Arima H, Yoshimatsu A, Ikeda H, Ohyama A, Motoyama K, Higashi T, et al. Folate-PEG-appended dendrimer conjugate with alpha-cyclodextrin as a novel cancer cell selective siRNA delivery carrier. Mol Pharm. 2012;9(9):2591–604.
Kwon O-J, Kang E, Choi J-W, Kim SW, Yun C-O. Therapeutic targeting of chitosan-PEG-folate-complexed oncolytic adenovirus for active and systemic cancer gene therapy. J Cont Rel. 2013;169(3):257–65.
Yao H, Chen S-C, Shen Z, Huang Y-C, Zhu X, Wang X-M, et al. Functional characterization of a PEI-CyD-FA-coated adenovirus as delivery vector for gene therapy. Curr Med Chem. 2013;20(20):2601–8.
Zhao F, Yin H, Zhang Z, Li J. Folic acid modified cationic gamma-Cyclodextrin-oligoethylenimine star polymer with bioreducible disulfide linker for efficient targeted gene delivery. Biomacromolecules. 2013;14(2):476–84.
Mornet E, Carmoy N, Laine C, Lemiegre L, Le Gall T, Laurent I, et al. Folate-equipped nanolipoplexes mediated efficient gene transfer into human epithelial cells. Int J Mol Sci. 2013;14(1):1477–501.
Meirovitz A, Goldberg R, Binder A, Rubinstein AM, Hermano E, Elkin M. Heparanase in inflammation and inflammation-associated cancer. Febs J. 2013;280(10):2307.
Fan Y, Mao R, Yang J. NF-kappa B and STAT3 signaling pathways collaboratively link inflammation to cancer. Protein Cell. 2013;4(3):176–85.
Kisielewski R, Tolwinska A, Mazurek A, Laudanski P. Inflammation and ovarian cancer—current views. Ginekol Pol. 2013;84(4):293–7.
Inagaki-ohara K, Kondo T, Ito M, Yoshimuura A. SOCS, inflammation, and cancer. JAK-STAT. 2013;2(3):e24053–63.
Rimessi A, Patergnani S, Loannidi E, Pinton P. Chemoresistance and cancer-related inflammation: two hallmarks of cancer connected by an atypical link, PKC(gamma). Front Oncol. 2013;3(232):1–7.
Cronstein BN, Naime D, Ostad E. The antiinflammatory mechanism of methotrexate—increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in-vivo model of inflammation. J Clin Investig. 1993;92(6):2675–82.
Furst DE, Kremer JM. Methotrexate in rheumatoid-arthritis. Arthritis Rheum. 1988;31(3):305–14.
Thomas TP, Goonewardena SN, Majoros IJ, Kotlyar A, Cao Z, Leroueil PR, et al. Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis. Arthritis Rheum. 2011;63(9):2671–80.
Zhou J, Tsai Y-T, Weng H, Baker DW, Tang L. Real time monitoring of biomaterial-mediated inflammatory responses via macrophage-targeting NIR nanoprobes. Biomaterials. 2011;32(35):9383–90.
Duchatelle V, Kritikou EA, Tardif J-C. Clinical value of drugs targeting inflammation for the management of coronary artery disease. Can J Cardiol. 2012;28(6):678–86.
Leuschner F, Dutta P, Gorbatov R, Novobrantseva TI, Donahoe JS, Courties G, et al. Therapeutic siRNA silencing in inflammatory monocytes in mice. Nat Biotechnol. 2011;29(11):1005–10.
Garg NK, Dwivedi P, Campbell C, Tyagi RK. Site specific/targeted delivery of gemcitabine through anisamide anchored chitosan/poly ethylene glycol nanoparticles: an improved understanding of lung cancer therapeutic intervention. Eur J Pharm Sci. 2012;47(5):1006–14.
Guo J, Ogier JR, Desgranges S, Darcy R, O’Driscoll C. Anisamide-targeted cyclodextrin nanoparticles for siRNA delivery to prostate tumours in mice. Biomaterials. 2012;33(31):7775–84.
Kim SK, Huang L. Nanoparticle delivery of a peptide targeting EGFR signaling. J Control Release. 2012;157(2):279–86.
Yang Y, Hu Y, Wang Y, Li J, Liu F, Huang L. Nanoparticle delivery of pooled siRNA for effective treatment of non-small cell lung caner. Mol Pharm. 2012;9(8):2280–9.
Zhang Y, Schwerbrock NMJ, Rogers AB, Kim WY, Huang L. Codelivery of VEGF siRNA and gemcitabine monophosphate in a single nanoparticle formulation for effective treatment of NSCLC. Mol Ther. 2013;21(8):1559–69.
Wang Y, Su H-H, Yang Y, Hu Y, Zhang L, Blancafort P, et al. Systemic delivery of modified mRNA encoding herpes simplex virus 1 thymidine kinase for targeted cancer gene therapy. Mol Ther. 2013;21(2):358–67.
Xie H, Diagaradjane P, Deorukhkar AA, Goins B, Bao A, Phillips WT, et al. Integrin alpha(v)beta(3)-targeted gold nanoshells augment tumor vasculature-specific imaging and therapy. Int J Nanomedicine. 2011;6:259–69.
Mokhtarieh AA, Kim S, Lee Y, Chung BH, Lee MK. Novel cell penetrating peptides with multiple motifs composed of RGD and its analogs. Biochem Biophys Res Commun. 2013;432(2):359–64.
Chen J-X, Xu X-D, Yang S, Yang J, Zhuo R-X, Zhang X-Z. Self-assembled BolA-like amphiphilic peptides as viral-mimetic gene vectors for cancer cell targeted gene delivery. Macromol Biosci. 2013;13(1):84–92.
Park J, Singha K, Son S, Kim J, Namgung R, Yun CO, et al. A review of RGD-functionalized nonviral gene delivery vectors for cancer therapy. Cancer Gene Ther. 2012;19(11):741–8.
Martin I, Dohmen C, Mas-Moruno C, Troiber C, Kos P, Schaffert D, et al. Solid-phase-assisted synthesis of targeting peptide-PEG-oligo(ethane amino)amides for receptormediated gene delivery. Org Biomol Chem. 2012;10(16):3258–68.
Liu S, Guo Y, Huang R, Li J, Huang S, Kuang Y, et al. Gene and doxorubicin co-delivery system for targeting therapy of glioma. Biomaterials. 2012;33(19):4907–16.
Wang X-L, Xu R, Wu X, Gillespie D, Jensen R, Lu Z-R. Targeted systemic delivery of a therapeutic siRNA with a multifunctional carrier controls tumor proliferation in mice. Mol Pharm. 2009;6(3):738–46.
Iwasaki T, Yamakawa M, Asaoka A, Kawano T, Ishibashi J. Anti-angiogenesis activities of novel peptide complexes: mitochondria-disruptive 9mer peptides conjugated with the integrin alpha V beta 3-homing cyclic RGD motif. Biosci Biotechnol Biochem. 2012;76(11):2044–8.
Miura Y, Takenaka T, Toh K, Wu S, Nishihara H, Kano MR, et al. Cyclic RGD-linked polymeric micelles for targeted delivery of platinum anticancer drugs to glioblastoma through the blood–brain tumor barrier. ACS Nano. 2013;7(10):8583–92.
Marelli UK, Rechenmacher F, Sobahi TRA, Mas-Moruno C, Kessler H. Tumor targeting via integrin ligands. Front Oncol. 2013;3(222):1–12.
Ferro-Flores G, Ramirez FM, Melendez-Alafort L, Santos-Cuevas CL. Peptides for in vivo target-specific cancer imaging. Mini-Rev Med Chem. 2010;10(1):87–97.
Ming X, Alam MR, Fisher M, Yan Y, Chen X, Juliano RL. Intracellular delivery of an antisense oligonucleotide via endocytosis of a G protein-coupled receptor. Nucleic Acids Res. 2010;38(19):6567–76.
Bleul R, Thiermann R, Marten GU, House MJ, St Pierre TG, Hafeli UO, et al. Continuously manufactured magnetic polymersomes—a versatile tool (not only) for targeted cancer therapy. Nanoscale. 2013;5(23):11385–93.
Accardo A, Mansi R, Salzano G, Morisco A, Aurilio M, Parisi A, et al. Bombesin peptide antagonist for target-selective delivery of liposomal doxorubicin on cancer cells. J Drug Target. 2013;21(3):240–9.
Burgus R, Ling N, Butcher M, Guillemi R. Primary structure of somatostatin—hypothalamic peptide that inhibits secretion of pituitary growth-hormone. Proc Natl Acad Sci U S A. 1973;70(3):684–8.
Reubi JC. New specific radioligand for one subpopulation of brain somatostatin receptors. Life Sci. 1985;36(19):1829–36.
Lattuada D, Casnici C, Crotta K, Mastrotto C, Franco P, Schmid HA, et al. Inhibitory effect of pasireotide and octreotide on lymphocyte activation. J Neuroimmunol. 2007;182(1–2):153–9.
Hershberger RE, Newman BL, Florio T, Bunzow J, Civelli O, Li XJ, et al. The somatostatin receptors Sstr1 and Sstr2 are coupled to inhibition of adenylyl-cyclase in Chinese-hamster ovary cells via pertussis-toxin-sensitive pathways. Endocrinology. 1994;134(3):1277–85.
Nurhidayat, Tsukamoto Y, Sigit K, Sasaki F. Sex differentiation of growth hormone-releasing hormone and somatostatin neurons in the mouse hypothalamus: an immunohistochemical and morphological study. Brain Res. 1999;821(2):309–21.
Kvols LK, Woltering EA. Role of somatostatin analogs in the clinical management of non-neuroendocrine solid tumors. Anti-Cancer Drugs. 2006;17(6):601–8.
Chen F, Odorisio MS, Hermann G, Hayes J, Malarkey WB, Odorisio TM. Mechanisms of action of long-acting analogs of somatostatin. Regul Pept. 1993;44(3):285–95.
Kaupmann K, Bruns C, Hoyer D, Seuwen K, Lubbert H. Distribution and 2nd messenger coupling of 4 somatostatin receptor subtypes expressed in brain. Febs Lett. 1993;331(1–2):53–9.
Patel YC, Greenwood MT, Panetta R, Demchyshyn L, Niznik H, Srikant CB. Mini review—the somatostatin receptor family. Life Sci. 1995;57(13):1249–65.
Surujpaul PP, Gutierrez-Wing C, Ocampo-Garcia B, Ramirez FM, de Murphy CA, Pedraza-Lopez M, et al. Gold nanoparticles conjugated to [Tyr(3)]Octreotide peptide. Biophys Chem. 2008;138(3):83–90.
Oyen WJG, Bodei L, Giammarile F, Maecke HR, Tennvall J, Luster M, et al. Targeted therapy in nuclear medicine-current status and future prospects. Ann Oncol. 2007;18(11):1782–92.
Imam SK. Molecular nuclear imaging: the radiopharmaceuticals (review). Cancer Biother Radiopharm. 2005;20(2):163–72.
Susini C, Buscail L. Rationale for the use of somatostatin analogs as antitumor agents. Ann Oncol. 2006;17(12):1733–42.
Pan X, Thompson R, Meng X, Wu D, Xu L. Tumor-targeted RNA-interference: functional non-viral nanovectors. Am J Cancer Res. 2011;1(1):25–42.
Shen H, Hu D, Du J, Wang X, Liu Y, Wang Y, et al. Paclitaxel-octreotide conjugates in tumor growth inhibition of A549 human non-small cell lung cancer xenografted into nude mice. Eur J Pharmacol. 2008;601(1–3):23–9.
Parry JJ, Eiblmaier M, Andrews R, Meyer LA, Higashikubo R, Anderson CJ, et al. Characterization of somatostatin receptor subtype 2 expression in stably transfected A-427 human cancer cells. Mol Imaging. 2007;6(1):56–67.
Parry JJ, Chen R, Andrews R, Lears KA, Rogers BE. Identification of critical residues involved in ligand binding and g protein signaling in human somatostatin receptor subtype 2. Endocrinology. 2012;153(6):2747–55.
Koper JW, Markstein R, Kohler C, Kwekkeboom DJ, Avezaat CJJ, Lamberts SWJ, et al. Somatostatin inhibits the activity of adenylate-cyclase in cultured human meningioma cells and stimulates their growth. J Clin Endocrinol Metab. 1992;74(3):543–7.
Fruhwald MC, O’Dorisio MS, Pietsch T, Reubi JC. High expression of somatostatin receptor subtype 2 (sst(2)) in medulloblastoma: Implications for diagnosis and therapy. Pediatr Res. 1999;45(5):697–708.
Hofland LJ, Vankoetsveld PM, Waaijers M, Zuyderwijk J, Breeman WAP, Lamberts SWJ. Internalization of the radioiodinated somatostatin analog [I-125-Tyr(3)]octreotide by mouse and human pituitary-tumor cells—increase by unlabeled octreotide. Endocrinology. 1995;136(9):3698–706.
Poell F, Lehmann D, Illing S, Ginj M, Jacobs S, Lupp A, et al. Pasireotide and octreotide stimulate distinct patterns of sst(2A) somatostatin receptor phosphorylation. Mol Endocrinol. 2010;24(2):436–46.
Bakker WH, Krenning EP, Breeman WA, Koper JW, Kooij PP, Reubi JC, et al. Receptor scintigraphy with a radioiodinated somatostatin analog—radiolabeling, purification, biologic activity, and invivo application in animals. J Nucl Med. 1990;31(9):1501–9.
Bushnell D, Menda Y, O’Dorisio T, Madsen M, Miller S, Carlisle T, et al. Effects of intravenous amino acid administration with Y-90 DOTA-Phe1-Ty3-octreotide (SMT487 [OctreoTher (TM)]) treatment. Cancer Biother Radiopharm. 2004;19(1):35–41.
Antunes P, Ginj M, Walter MA, Chen J, Reubi J-C, Maecke HR. Influence of different spacers on the biological profile of a DOTA-somatostatin analogue. Bioconjug Chem. 2007;18(1):84–92.
Eberle AN, Mild G. Receptor-mediated tumor targeting with radiopeptides Part 1. General principles and methods. J Recept Signal Transduct. 2009;29(1):1–37.
Schottelius M, Wester H-J. Molecular imaging targeting peptide receptors. Methods. 2009;48(2):161–77.
Reubi JC, Maecke HR. Peptide-based probes for cancer imaging. J Nucl Med. 2008;49(11):1735–8.
Vaidyanathan G, Affleck DJ, Norman J, O’Dorisio S, Zalutsky MR. A radloiodinated MEBG-octreotate conjugate exhibiting enhanced uptake and reten tion in SSTR2-expressing tumor cells. Bioconjug Chem. 2007;18(6):2122–30.
Zhang Y, Zhang H, Wang X, Wang J, Zhang X, Zhang Q. The eradication of breast cancer and cancer stem cells using octreotide modified paclitaxel active targeting micelles and salinomycin passive targeting micelles. Biomaterials. 2012;33(2):679–91.
Niu J, Su Z, Xiao Y, Huang A, Li H, Bao X, et al. Octreotide-modified and pH-triggering polymeric micelles loaded with doxorubicin for tumor targeting delivery. Eur J Pharm Sci. 2012;45(1–2):216–26.
Guo Y, Ferdani R, Anderson CJ. Preparation and biological evaluation of Cu-64 labeled Tyr(3)-octreotate using a phosphonic acid-based cross-bridged macrocyclic chelator. Bioconjug Chem. 2012;23(7):1470–7.
Dai W, Jin W, Zhang J, Wang X, Wang J, Zhang X, et al. Spatiotemporally controlled co-delivery of anti-vasculature agent and cytotoxic drug by octreotide-modified stealth liposomes. Pharm Res. 2012;29(10):2902–11.
Xiao Y, Jaskula-Sztul R, Javadi A, Xu W, Eide J, Dammalapati A, et al. Co-delivery of doxorubicin and siRNA using octreotide-conjugated gold nanorods for targeted neuroendocrine cancer therapy. Nanoscale. 2012;4(22):7185–93.
Lecolle K, Begard S, Caillierez R, Demeyer D, Grellier E, Loyens A, et al. Sstr2A: a relevant target for the delivery of genes into human glioblastoma cells using fibermodified adenoviral vectors. Gene Ther. 2013;20(3):283–97.
Xu LP, Josan JS, Vagner J, Caplan MR, Hruby VJ, Mash EA, et al. Heterobivalent ligands target cell-surface receptor combinations in vivo. Proc Natl Acad Sci U S A. 2012;109(52):21295–300.
Ortner A, Wernig K, Kaisler R, Edetsberger M, Hajos F, Koehler G, et al. VPAC receptor mediated tumor cell targeting by protamine based nanoparticles. J Drug Target. 2010;18(6):457–67.
Liu Z, Stanojevic V, Brindamour LJ, Habener JF. GLP1-derived nonapeptide GLP1(28–36)amide protects pancreatic beta-cells from glucolipotoxicity. J Endocrinol. 2012;213(2):143–54.
Tafreshi NK, Huang X, Moberg VE, Barkey NM, Sondak VK, Tian H, et al. Synthesis and characterization of a melanoma-targeted fluorescence imaging probe by conjugation of a melanocortin 1 receptor (MC1R) specific ligand. Bioconjug Chem. 2012;23(12):2451–9.
Falciani C, Brunetti J, Lelli B, Accardo A, Tesauro D, Morelli G, et al. Nanoparticles exposing neurotensin tumor-specific drivers. J Pept Sci. 2013;19(4):198–204.
Rangger C, Helbok A, Ocak M, Radolf T, Andreae F, Virgolini II, et al. Design and evaluation of novel radiolabelled VIP derivatives for tumour targeting. Anticancer Res. 2013;33(4):1537–46.
Xu Y, Duggineni S, Espitia S, Richman DD, An J, Huang Z. A synthetic bivalent ligand of CXCR4 inhibits HIV infection. Biochem Biophys Res Commun. 2013;435(4):646–50.
Odorisio MS, Fleshman DJ, Qualman SJ, Odorisio TM. Vasoactive-intestinal-peptide - autocrine growth-factor in neuroblastoma. Regul Pept. 1992;37(3):213–26.
Khondee S, Baoum A, Siahaan TJ, Berkland C. Calcium condensed LABL-TAT complexes effectively target gene delivery to ICAM-1 expressing cells. Mol Pharm. 2011;8(3):788–98.
Blackburn WH, Dickerson EB, Smith MH, McDonald JF, Lyon LA. Peptide-functionalized nanogels for targeted siRNA delivery. Bioconjug Chem. 2009;20(5):960–8.
Angata T, Fujinawa R, Kurimoto A, Nakajima K, Kato M, Takamatsu S, et al. Integrated approach toward the discovery of glyco-biomarkers of inflammation-related diseases. Glycobiology of the immune response. Ann N Y Acad Sci. 2012;1253:159–69.
Pirogova E, Istivan T, Gan E, Cosic I. Advances in methods for therapeutic peptide discovery. Design and development. Curr Pharm Biotechnol. 2011;12(8):1117–27.
Liu BA, Engelmann BW, Nash PD. High-throughput analysis of peptide-binding modules. Proteomics. 2012;12(10):1527–46.
Levine RM, Scott CM, Kokkoli E. Peptide functionalized nanoparticles for nonviral gene delivery. Soft Matter. 2013;9(4):985–1004.
Author information
Authors and Affiliations
Corresponding author
Additional information
Guest Editors: Mahavir B. Chougule and Chalet Tan
Rights and permissions
About this article
Cite this article
Duskey, J.T., Rice, K.G. Nanoparticle Ligand Presentation for Targeting Solid Tumors. AAPS PharmSciTech 15, 1345–1354 (2014). https://doi.org/10.1208/s12249-014-0143-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1208/s12249-014-0143-6