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Multifunctional nanoparticles for use in theranostic applications

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Abstract

Theranostics is a promising field that combines therapeutics and diagnostics into single multifunctional formulations. This field is driven by advancements in nanoparticle systems capable of providing the necessary functionalities. By utilizing these powerful nanomedicines, the concept of personalized medicine can be realized by tailoring treatment strategies to the individual. This review gives a brief overview of the components of a theranostic system and the challenges that designing truly multifunctional nanoparticles present. Considerations when choosing a class of nanoparticle include the size, shape, charge, and surface chemistry, while classes of nanoparticles discussed are polymers, liposomes, dendrimers, and polymeric micelles. Targeting to disease states can be achieved either through passive or active targeting which uses specific ligands to target receptors that are overexpressed in tumors and common targeting elements are presented. To image the interactions with disease states, contrast agents are included in the nanoparticle formulation. Imaging options include optical imaging techniques, computed tomography, nuclear based, and magnetic resonance imaging. The interplay between all of these components needs to be carefully considered when designing a theranostic system.

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References

  1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA: Cancer J Clin. 2014;64(1):9–29.

    Google Scholar 

  2. DeSantis CE, Lin CC, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2014. CA-Cancer J Clin. 2014;64(4):252–71.

    Article  PubMed  Google Scholar 

  3. Sahoo S, Labhasetwar V. Nanotech approaches to delivery and imaging drug. Drug Discov Today. 2003;8(24):1112–20.

    Article  CAS  PubMed  Google Scholar 

  4. Cheng Z, Al Zaki A, Hui JZ, Muzykantov VR, Tsourkas A. Multifunctional nanoparticles: cost versus benefit of adding targeting and imaging capabilities. Science. 2012;338(6109):903–10.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Kelkar SS, Reineke TM. Theranostics: combining imaging and therapy. Bioconjug Chem. 2011;22(10):1879–903.

    Article  CAS  PubMed  Google Scholar 

  6. Ryu JH, Lee S, Son S, et al. Theranostic nanoparticles for future personalized medicine. J Control Release. 2014;190:477–84.

    Article  CAS  PubMed  Google Scholar 

  7. Kalia M et al. Personalized oncology: recent advances and future challenges. Metab, Clin Exp. 2013;62:S11–4.

    Article  CAS  Google Scholar 

  8. McGeough C, Bjourson A. Diagnostic, prognostic and theranostic genetic biomarkers for rheumatoid arthritis. J Clin Cell Immuno. 2012;6(002):1–5.

    Google Scholar 

  9. Gelderblom H, Verweij J, Nooter K, Sparreboom A, Cremophor EL. The drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer. 2001;37(13):1590–8.

    Article  CAS  PubMed  Google Scholar 

  10. Cho K, Wang X, Nie S, Chen Z, Shin DM. Therapeutic nanoparticles for drug delivery in cancer. Clin Cancer Res. 2008;14(5):1310–6.

    Article  CAS  PubMed  Google Scholar 

  11. Allen T, Cullis P. Drug delivery systems: entering the mainstream. Science. 2004;303(5665):1818–22.

    Article  CAS  PubMed  Google Scholar 

  12. Davis ME, Chen Z, Shin DM. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov. 2008;7(9):771–82.

    Article  CAS  PubMed  Google Scholar 

  13. Brannon-Peppas L, Blanchette J. Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev. 2004;56(11):1649–59.

    Article  CAS  PubMed  Google Scholar 

  14. Kamaly N, Xiao Z, Valencia PM, Radovic-Moreno AF, Farokhzad OC. Targeted polymeric therapeutic nanoparticles: design, development and clinical translation. Chem Soc Rev. 2012;41(7):2971–3010.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Zhang S, Li J, Lykotrafitis G, Bao G, Suresh S. Size-dependent endocytosis of nanoparticles. Adv Mater. 2009;21(4):419.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  16. Sahay G, Alakhova DY, Kabanov AV. Endocytosis of nanomedicines. J Control Release. 2010;145(3):182–95.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Gratton SEA, Ropp PA, Pohlhaus PD, et al. The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci U S A. 2008;105(33):11613–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Wang J, Byrne JD, Napier ME, DeSimone JM. More effective nanomedicines through particle design. Small. 2011;7(14):1919–31.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Choi HS, Liu W, Misra P, et al. Renal clearance of quantum dots. Nat Biotechnol. 2007;25(10):1165–70.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Moghimi SM, Szebeni J. Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. Prog Lipid Res. 2003;42(6):463–78.

    Article  CAS  PubMed  Google Scholar 

  21. Torchilin VP. Micellar nanocarriers: pharmaceutical perspectives. Pharm Res. 2007;24(1):1–16.

    Article  CAS  PubMed  Google Scholar 

  22. Geng Y, Dalhaimer P, Cai S, et al. Shape effects of filaments versus spherical particles in flow and drug delivery. Nat Nanotechnol. 2007;2(4):249–55.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Verma A, Stellacci F. Effect of surface properties on nanoparticle-cell interactions. Small. 2010;6(1):12–21.

    Article  CAS  PubMed  Google Scholar 

  24. Toy R, Bauer L, Hoimes C, Ghaghada KB, Karathanasis E. Targeted nanotechnology for cancer imaging. Adv Drug Deliv Rev. 2014;76:79–97.

    Article  CAS  PubMed  Google Scholar 

  25. Doshi N, Prabhakarpandian B, Rea-Ramsey A, Pant K, Sundaram S, Mitragotri S. Flow and adhesion of drug carriers in blood vessels depend on their shape: a study using model synthetic microvascular networks. J Control Release. 2010;146(2):196–200.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Decuzzi P, Godin B, Tanaka T, et al. Size and shape effects in the biodistribution of intravascularly injected particles. J Control Release. 2010;141(3):320–7.

    Article  CAS  PubMed  Google Scholar 

  27. Zhao F, Zhao Y, Liu Y, Chang X, Chen C, Zhao Y. Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Small. 2011;7(10):1322–37.

    Article  CAS  PubMed  Google Scholar 

  28. Wilhelm C, Billotey C, Roger J, Pons JN, Bacri JC, Gazeau F. Intracellular uptake of anionic superparamagnetic nanoparticles as a function of their surface coating. Biomaterials. 2003;24(6):1001–11.

    Article  CAS  PubMed  Google Scholar 

  29. Dausend J, Musyanovych A, Dass M, et al. Uptake mechanism of oppositely charged fluorescent nanoparticles in HeLa cells. Macromol Biosci. 2008;8(12):1135–43.

    Article  CAS  PubMed  Google Scholar 

  30. Karmali PP, Simberg D. Interactions of nanoparticles with plasma proteins: implication on clearance and toxicity of drug delivery systems. Expert Opin Drug Deliv. 2011;8(3):343–57.

    Article  CAS  PubMed  Google Scholar 

  31. Vonarbourg A, Passirani C, Saulnier P, Benoit JP. Parameters influencing the stealthiness of colloidal drug delivery systems. Biomaterials. 2006;27(24):4356–73.

    Article  CAS  PubMed  Google Scholar 

  32. Veronese FM, Pasut G. PEGylation, successful approach to drug delivery. Drug Discov Today. 2005;10(21):1451–8.

    Article  CAS  PubMed  Google Scholar 

  33. Soppimath K, Aminabhavi T, Kulkarni A, Rudzinski W. Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release. 2001;70(1–2):1–20.

    Article  CAS  PubMed  Google Scholar 

  34. Agnihotri S, Mallikarjuna N, Aminabhavi T. Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J Control Release. 2004;100(1):5–28.

    Article  CAS  PubMed  Google Scholar 

  35. Bala I, Hariharan S, Kumar M. PLGA nanoparticles in drug delivery: the state of the art. Crit Rev Ther Drug Carrier Syst. 2004;21(5):387–422.

    Article  CAS  PubMed  Google Scholar 

  36. Gu F, Zhang L, Teply BA, et al. Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers. Proc Natl Acad Sci U S A. 2008;105(7):2586–91.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Malam Y, Loizidou M, Seifalian AM. Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer. Trends Pharmacol Sci. 2009;30(11):592–9.

    Article  CAS  PubMed  Google Scholar 

  38. Zhang H, Ma Y, Sun X. Chemically-selective surface glyco-functionalization of liposomes through staudinger ligation. Chem Commun. 2009;21:3032–4.

    Article  CAS  Google Scholar 

  39. Noble GT, Stefanick JF, Ashley JD, Kiziltepe T, Bilgicer B. Ligand-targeted liposome design: challenges and fundamental considerations. Trends Biotechnol. 2014;32(1):32–45.

    Article  CAS  PubMed  Google Scholar 

  40. Al-Jamal WT, Kostarelos K. Liposomes: from a clinically established drug delivery system to a nanoparticle platform for theranostic nanomedicine. Acc Chem Res. 2011;44(10):1094–104.

    Article  CAS  PubMed  Google Scholar 

  41. Allen TM, Cullis PR. Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev. 2013;65(1):36–48.

    Article  CAS  PubMed  Google Scholar 

  42. Astruc D, Boisselier E, Ornelas C. Dendrimers designed for functions: from physical, photophysical, and supramolecular properties to applications in sensing, catalysis, molecular electronics, photonics, and nanomedicine. Chem Rev. 2010;110(4):1857–959.

    Article  CAS  PubMed  Google Scholar 

  43. Kaminskas LM, Boyd BJ, Porter CJH. Dendrimer pharmacokinetics: the effect of size, structure and surface characteristics on ADME properties. Nanomedicine. 2011;6(6):1063–84.

    Article  CAS  PubMed  Google Scholar 

  44. Oerlemans C, Bult W, Bos M, Storm G, Nijsen JFW, Hennink WE. Polymeric micelles in anticancer therapy: targeting, imaging and triggered release. Pharm Res. 2010;27(12):2569–89.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Matsumura Y. Preclinical and clinical studies of NK012, an SN-38-incorporating polymeric micelles, which is designed based on EPR effect. Adv Drug Deliv Rev. 2011;63(3):184–92.

    Article  CAS  PubMed  Google Scholar 

  46. Sutton D, Nasongkla N, Blanco E, Gao J. Functionalized micellar systems for cancer targeted drug delivery. Pharm Res. 2007;24(6):1029–46.

    Article  CAS  PubMed  Google Scholar 

  47. Http://www.doxil.com/.

  48. Nagore E, Insa A, Sanmartin O. Antineoplastic therapy-induced palmar plantar erythrodysesthesia (‘hand-foot’) syndrome. Incidence, recognition and management. Am J Clin Dermatol. 2000;1(4):225–34.

    Article  CAS  PubMed  Google Scholar 

  49. Longhi A, Ferrari S, Bacci G, Specchia S. Long-term follow-up of patients with doxorubicin-induced cardiac toxicity after chemotherapy for osteosarcoma. Anticancer Drugs. 2007;18(6):737–44.

    Article  CAS  PubMed  Google Scholar 

  50. Goto S, Ihara Y, Urata Y, et al. Doxorubicin-induced DNA intercalation and scavenging by nuclear glutathione S-transferase pi. FASEB J. 2001;15(14):2702–14.

    Article  CAS  PubMed  Google Scholar 

  51. Thorn CF, Oshiro C, Marsh S, et al. Doxorubicin pathways: pharmacodynamics and adverse effects. Pharmacogenet Genom. 2011;21(7):440–6.

    Article  CAS  Google Scholar 

  52. Cho H, Yoon I, Yoon HY, et al. Polyethylene glycol-conjugated hyaluronic acid-ceramide self-assembled nanoparticles for targeted delivery of doxorubicin. Biomaterials. 2012;33(4):1190–200.

    Article  CAS  PubMed  Google Scholar 

  53. Rowinsky E, Donehower R. Drug-therapy—paclitaxel (taxol). N Engl J Med. 1995;332(15):1004–14.

    Article  CAS  PubMed  Google Scholar 

  54. Spencer C, Faulds D. Paclitaxel—a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of cancer. Drugs. 1994;48(5):794–847.

    Article  CAS  PubMed  Google Scholar 

  55. Lanza G, Yu X, Winter P, et al. Targeted antiproliferative drug delivery to vascular smooth muscle cells with a magnetic resonance imaging nanoparticle contrast agent implications for rational therapy of restenosis. Circulation. 2002;106(22):2842–7.

    Article  CAS  PubMed  Google Scholar 

  56. Redis RS, Berindan-Neagoe I, Pop VI, Calin GA. Non-coding RNAs as theranostics in human cancers. J Cell Biochem. 2012;113(5):1451–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  57. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.

    Article  CAS  PubMed  Google Scholar 

  58. Calin GA, Dumitru CD, Shimizu M, et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002;99(24):15524–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Hatley ME, Patrick DM, Garcia MR, et al. Modulation of K-ras-dependent lung tumorigenesis by microRNA-21. Cancer Cell. 2010;18(3):282–93.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Zhao J, Lin J, Yang H, et al. MicroRNA-221/222 negatively regulates estrogen receptor alpha and is associated with tamoxifen resistance in breast cancer. J Biol Chem. 2008;283(45):31079–86.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Fujita Y, Kojima K, Hamada N, et al. Effects of miR-34a on cell growth and chemoresistance in prostate cancer PC3 cells. Biochem Biophys Res Commun. 2008;377(1):114–9.

    Article  CAS  PubMed  Google Scholar 

  62. Chen Y, Zhu X, Zhang X, Liu B, Huang L. Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy. Mol Ther. 2010;18(9):1650–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Kim J, Yeom J, Ko J, et al. Effective delivery of anti-miRNA DNA oligonucleotides by functionalized gold nanoparticles. J Biotechnol. 2011;155(3):287–92.

    Article  CAS  PubMed  Google Scholar 

  64. Oh Y, Park TG. siRNA delivery systems for cancer treatment. Adv Drug Deliv Rev. 2009;61(10):850–62.

    Article  CAS  PubMed  Google Scholar 

  65. Peer D, Park EJ, Morishita Y, Carman CV, Shimaoka M. Systemic leukocyte-directed siRNA delivery revealing cyclin D1 as an anti-inflammatory target. Science. 2008;319(5863):627–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. Schiffelers RM, Storm G. ICS-283: a system for targeted intravenous delivery of siRNA. Expert Opin Drug Deliv. 2006;3(3):445–54.

    Article  CAS  PubMed  Google Scholar 

  67. Barenholz Y. Doxil (R)—the first FDA-approved nano-drug: lessons learned. J Control Release. 2012;160(2):117–34.

    Article  CAS  PubMed  Google Scholar 

  68. O'Brien M, Wigler N, Inbar M, et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX (TM)/doxil (R)) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004;15(3):440–9.

    Article  PubMed  Google Scholar 

  69. Forssen EA, Ross ME. Daunoxome treatment of solid tumors: preclinical and clinical investigations. J Liposome Res. 1994;4(1):481–512.

    Article  Google Scholar 

  70. Green MR, Manikhas GM, Orlov S, et al. Abraxane((R)), a novel Cremophor((R))-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Ann Oncol. 2006;17(8):1263–8.

    Article  CAS  PubMed  Google Scholar 

  71. Melmed GY, Targan SR, Yasothan U, Hanicq D, Kirkpatrick P. Certolizumab pegol. Nat Rev Drug Discov. 2008;7(8):641–2.

    Article  CAS  PubMed  Google Scholar 

  72. Berges R. Eligard (R): pharmacokinetics, effect on testosterone and PSA levels and tolerability. Eur Urol Suppl. 2005;4(5):20–5.

    Article  CAS  Google Scholar 

  73. Dinndorf PA, Gootenberg J, Cohen MH, Keegan P, Pazdur R. FDA drug approval summary: pegaspargase (Oncaspar (R)) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). Oncologist. 2007;12(8):991–8.

    Article  CAS  PubMed  Google Scholar 

  74. Kim T, Kim D, Chung J, et al. Phase I and pharmacokinetic study of genexol-PM, a cremophor-free, polymeric micelle-formulated paclitaxel, in patients with advanced malignancies. Clin Cancer Res. 2004;10(11):3708–16.

    Article  CAS  PubMed  Google Scholar 

  75. Hamaguchi T, Matsumura Y, Suzuki M, et al. NK105, a paclitaxel-incorporating micellar nanoparticle formulation, can extend in vivo antitumour activity and reduce the neurotoxicity of paclitaxel. Br J Cancer. 2005;92(7):1240–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Plummer R, Wilson RH, Calvert H, et al. A phase I clinical study of cisplatin-incorporated polymeric micelles (NC-6004) in patients with solid tumours. Br J Cancer. 2011;104(4):593–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Danson S, Ferry D, Alakhov V, et al. Phase I dose escalation and pharmacokinetic study of pluronic polymer-bound doxorubicin (SP 1049C) in patients with advanced cancer. Br J Cancer. 2004;90(11):2085–91.

    PubMed Central  CAS  PubMed  Google Scholar 

  78. Matsumura Y, Hamaguchi T, Ura T, et al. Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin. Br J Cancer. 2004;91(10):1775–81.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  79. Maeda H, Greish K, Fang J. The EPR effect and polymeric drugs: a paradigm shift for cancer chemotherapy in the 21st century. Adv Polym Sci. 2006;193:103–21.

    Article  CAS  Google Scholar 

  80. Kobayashi H, Watanabe R, Choyke PL. Improving conventional enhanced permeability and retention (EPR) effects; what is the appropriate target? Theranostics. 2014;4(1):81–9.

    Article  PubMed Central  CAS  Google Scholar 

  81. Maruyama K. Intracellular targeting delivery of liposomal drugs to solid tumors based on EPR effects. Adv Drug Deliv Rev. 2011;63(3):161–9.

    Article  CAS  PubMed  Google Scholar 

  82. Acharya S, Sahoo SK. PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Adv Drug Deliv Rev. 2011;63(3):170–83.

    Article  CAS  PubMed  Google Scholar 

  83. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release. 2000;65(1–2):271–84.

    Article  CAS  PubMed  Google Scholar 

  84. Heldin C, Rubin K, Pietras K, Ostman A. High interstitial fluid pressure—an obstacle in cancer therapy. Nat Rev Cancer. 2004;4(10):806–13.

    Article  CAS  PubMed  Google Scholar 

  85. Maeda H. Vascular permeability in cancer and infection as related to macromolecular drug delivery, with emphasis on the EPR effect for tumor-selective drug targeting. Proc Jpn Acad Ser B Phys Biol Sci. 2012;88(3):53–71.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  86. Moghimi S, Hunter A, Murray J. Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev. 2001;53(2):283–318.

    CAS  PubMed  Google Scholar 

  87. Peer D, Karp JM, Hong S, FaroKHzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2007;2(12):751–60.

    Article  CAS  PubMed  Google Scholar 

  88. Baselga J, Norton L, Albanell J, Kim Y, Mendelsohn J. Recombinant humanized anti-HER2 antibody (herceptin (TM)) enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res. 1998;58(13):2825–31.

    CAS  PubMed  Google Scholar 

  89. Zhang X, Eden HS, Chen X. Peptides in cancer nanomedicine: drug carriers, targeting ligands and protease substrates. J Control Release. 2012;159(1):2–13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  90. Hong S, Leroueil PR, Majoros IJ, Orr BG, Baker Jr JR, Holl MMB. The binding avidity of a nanoparticle-based multivalent targeted drug delivery platform. Chem Biol. 2007;14(1):107–15.

    Article  CAS  PubMed  Google Scholar 

  91. Pasqualini R, Ruoslahti E. Organ targeting in vivo using phage display peptide libraries. Nature. 1996;380(6572):364–6.

    Article  CAS  PubMed  Google Scholar 

  92. 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.

    Article  CAS  PubMed  Google Scholar 

  93. Http://Meetinglibrary.asco.org/content/32235-65.

  94. Phan A, Takimoto C, Adinin R, et al. Open label phase I study of MBP-426, a novel formulation of oxaliplatin, in patients with advanced or metastatic solid tumors. Mol Cancer Ther. 2007;6(12):3563S–4.

    Google Scholar 

  95. Senzer N, Nemunaitis J, Nemunaitis D, et al. Phase I study of a systemically delivered p53 nanoparticle in advanced solid tumors. Mol Ther. 2013;21(5):1096–103.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  96. Matsumura Y, Gotoh M, Muro K, et al. Phase I and pharmacokinetic study of MCC-465, a doxorubicin (DXR) encapsulated in PEG immunoliposome, in patients with metastatic stomach cancer. Ann Oncol. 2004;15(3):517–25.

    Article  CAS  PubMed  Google Scholar 

  97. Pittet L, Altreuter D, Ilyinskii P, et al. Development and preclinical evaluation of SEL-068, a novel targeted synthetic vaccine particle (tSVP (TM)) for smoking cessation and relapse prevention that generates high titers of antibodies against nicotine. J Immunol. 2012;188.

  98. Von Hoff DD, Mita M, Eisenberg P, et al. A phase I study of BIND-014, a PSMA-targeted nanoparticle containing docetaxel, in patients with refractory solid tumors. Cancer Res. 2013;73(8):85–6.

    Google Scholar 

  99. Patel O, Shulkes A, Baldwin GS. Gastrin-releasing peptide and cancer. Biochim Biophys Acta-Rev Cancer. 2006;1766(1):23–41.

    Article  CAS  Google Scholar 

  100. Wang RE, Niu Y, Wu H, Amin MN, Cai J. Development of NGR peptide-based agents for tumor imaging. Am J Nucl Med Mol Imaging. 2011;1(1):36–46.

    PubMed Central  CAS  PubMed  Google Scholar 

  101. Hersel U, Dahmen C, Kessler H. RGD modified polymers: biomaterials for stimulated cell adhesion and beyond. Biomaterials. 2003;24(24):4385–415.

    Article  CAS  PubMed  Google Scholar 

  102. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9(6):669–76.

    Article  CAS  PubMed  Google Scholar 

  103. Kitamura K, Takahashi T, Yamaguchi T, et al. Chemical-engineering of the monoclonal antibody-A7 by polyethylene-glycol for targeting cancer-chemotherapy. Cancer Res. 1991;51(16):4310–5.

    CAS  PubMed  Google Scholar 

  104. Laginha KM, Moase EH, Yu N, Huang A, Allen TM. Bioavailability and therapeutic efficacy of HER2 scFv-targeted liposomal doxorubicin in a murine model of HER2-overexpressing breast cancer. J Drug Target. 2008;16(7–8):605–10.

    Article  CAS  PubMed  Google Scholar 

  105. Sudimack J, Lee R. Targeted drug delivery via the folate receptor. Adv Drug Deliv Rev. 2000;41(2):147–62.

    Article  CAS  PubMed  Google Scholar 

  106. Huang C, Lo C, Chen H, Hsiue G. Multifunctional micelles for cancer cell targeting, distribution imaging, and anticancer drug delivery. Adv Funct Mater. 2007;17(14):2291–7.

    Article  CAS  Google Scholar 

  107. Qian Z, Li H, Sun H, Ho K. Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway. Pharmacol Rev. 2002;54(4):561–87.

    Article  CAS  PubMed  Google Scholar 

  108. Ghosh A, Heston WDW. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem. 2004;91(3):528–39.

    Article  CAS  PubMed  Google Scholar 

  109. Yarden Y. The EGFR family and its ligands in human cancer: signalling mechanisms and therapeutic opportunities. Eur J Cancer. 2001;37:S3–8.

    Article  CAS  PubMed  Google Scholar 

  110. Shen M, Gong F, Pang P, et al. An MRI-visible non-viral vector for targeted bcl-2 siRNA delivery to neuroblastoma. Int J Nanomed. 2012;7:3319–32.

    Article  CAS  Google Scholar 

  111. Wang H, Wang S, Liao Z, et al. Folate-targeting magnetic core-shell nanocarriers for selective drug release and imaging. Int J Pharm. 2012;430(1–2):342–9.

    Article  CAS  PubMed  Google Scholar 

  112. Swanson SD, Kukowska-Latallo JF, Patri AK, et al. Targeted gadolinium-loaded dendrimer nanoparticles for tumor-specific magnetic resonance contrast enhancement. Int J hNanomed. 2008;3(2):201–10.

    CAS  Google Scholar 

  113. Guthi JS, Yang S, Huang G, et al. MRI-visible micellar nanomedicine for targeted drug delivery to lung cancer cells. Mol Pharm. 2010;7(1):32–40.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  114. Lu P, Chen Y, Ou T, et al. Multifunctional hollow nanoparticles based on graft-diblock copolymers for doxorubicin delivery. Biomaterials. 2011;32(8):2213–21.

    Article  CAS  PubMed  Google Scholar 

  115. Kim Y, Jeon J, Hong SH, et al. Tumor targeting and imaging using cyclic RGD-PEGylated gold nanoparticle probes with directly conjugated iodine-125. Small. 2011;7(14):2052–60.

    Article  CAS  PubMed  Google Scholar 

  116. Morales-Avila E, Ferro-Flores G, Ocampo-Garcia BE, et al. Multimeric system of tc-99 m-labeled gold nanoparticles conjugated to c[RGDfK(C)] for molecular imaging of tumor alpha(v)beta(3) expression. Bioconjug Chem. 2011;22(5):913–22.

    Article  CAS  PubMed  Google Scholar 

  117. Pressly ED, Pierce RA, Connal LA, Hawker CJ, Liu Y. Nanoparticle PET/CT imaging of natriuretic peptide clearance receptor in prostate cancer. Bioconjug Chem. 2013;24(2):196–204.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  118. Benezra M, Penate-Medina O, Zanzonico PB, et al. Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma. J Clin Invest. 2011;121(7):2768–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  119. Chanda N, Kattumuri V, Shukla R, et al. Bombesin functionalized gold nanoparticles show in vitro and in vivo cancer receptor specificity. Proc Natl Acad Sci U S A. 2010;107(19):8760–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  120. Kim D, Jeong YY, Jon S. A drug-loaded aptamer-gold nanoparticle bioconjugate for combined CT imaging and therapy of prostate cancer. ACS Nano. 2010;4(7):3689–96.

    Article  CAS  PubMed  Google Scholar 

  121. Wang H, Zheng L, Peng C, Shen M, Shi X, Zhang G. Folic acid-modified dendrimer-entrapped gold nanoparticles as nanoprobes for targeted CT imaging of human lung adencarcinoma. Biomaterials. 2013;34(2):470–80.

    Article  CAS  PubMed  Google Scholar 

  122. Kinsella JM, Jimenez RE, Karmali PP, et al. X-ray computed tomography imaging of breast cancer by using targeted peptide-labeled bismuth sulfide nanoparticles. Angew Chem -Int Edit. 2011;50(51):12308–11.

    Article  CAS  Google Scholar 

  123. Bagalkot V, Zhang L, Levy-Nissenbaum E, et al. Quantum dot-aptamer conjugates for synchronous cancer imaging, therapy, and sensing of drug delivery based on bi-fluorescence resonance energy transfer. Nano Lett. 2007;7(10):3065–70.

    Article  CAS  PubMed  Google Scholar 

  124. Mulder WJM, Castermans K, van Beijnum JR, et al. Molecular imaging of tumor angiogenesis using alpha v beta 3-integrin targeted multimodal quantum dots. Angiogenesis. 2009;12(1):17–24.

    Article  CAS  PubMed  Google Scholar 

  125. Veiseh O, Sun C, Gunn J, et al. Optical and MRI multifunctional nanoprobe for targeting gliomas. Nano Lett. 2005;5(6):1003–8.

    Article  CAS  PubMed  Google Scholar 

  126. Wu W, Shen J, Banerjee P, Zhou S. Core-shell hybrid nanogels for integration of optical temperature-sensing, targeted tumor cell imaging, and combined chemo-photothermal treatment. Biomaterials. 2010;31(29):7555–66.

    Article  CAS  PubMed  Google Scholar 

  127. Olson ES, Jiang T, Aguilera TA, et al. Activatable cell penetrating peptides linked to nanoparticles as dual probes for in vivo fluorescence and MR imaging of proteases. Proc Natl Acad Sci U S A. 2010;107(9):4311–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  128. Yu MK, Park J, Jon S. Targeting strategies for multifunctional nanoparticles in cancer imaging and therapy. Theranostics. 2012;2(1):3–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  129. Maloney D, GrilloLopez A, White C, et al. IDEC-C2B8 (rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood. 1997;90(6):2188–95.

    CAS  PubMed  Google Scholar 

  130. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350(23):2335–42.

    Article  CAS  PubMed  Google Scholar 

  131. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351(4):337–45.

    Article  CAS  PubMed  Google Scholar 

  132. Nygren P. Alternative binding proteins: affibody binding proteins developed from a small three-helix bundle scaffold. Febs J. 2008;275(11):2668–76.

    Article  CAS  PubMed  Google Scholar 

  133. Ponka P, Lok C. The transferrin receptor: role in health and disease. Int J Biochem Cell Biol. 1999;31(10):1111–37.

    Article  CAS  PubMed  Google Scholar 

  134. Anabousi S, Bakowsky U, Schneider M, Huwer H, Lehr C, Ehrhardt C. In vitro assessment of transferrin-conjugated liposomes as drug delivery systems for inhalation therapy of lung cancer. Eur J Pharm Sci. 2006;29(5):367–74.

    Article  CAS  PubMed  Google Scholar 

  135. Sahoo SK, Ma W, Labhasetwar V. Efficacy of transferrin-conjugated paclitaxel-loaded nanoparticles in a murine model of prostate cancer. Int J Cancer. 2004;112(2):335–40.

    Article  CAS  PubMed  Google Scholar 

  136. Daniels TR, Bernabeu E, Rodriguez JA, et al. The transferrin receptor and the targeted delivery of therapeutic agents against cancer. Biochim Biophys Acta-Gen Subj. 2012;1820(3):291–317.

    Article  CAS  Google Scholar 

  137. Nilsson F, Tarli L, Viti F, Neri D. The use of phage display for the development of tumour targeting agents. Adv Drug Deliv Rev. 2000;43(2–3):165–96.

    Article  CAS  PubMed  Google Scholar 

  138. Low PS, Kularatne SA. Folate-targeted therapeutic and imaging agents for cancer. Curr Opin Chem Biol. 2009;13(3):256–62.

    Article  CAS  PubMed  Google Scholar 

  139. Watanabe K, Kaneko M, Maitani Y. Functional coating of liposomes using a folate-polymer conjugate to target folate receptors. Int J Nanomedicine. 2012;7:3679–88.

    PubMed Central  CAS  PubMed  Google Scholar 

  140. Hilgenbrink A, Low P. Folate receptor-mediated drug targeting: from therapeutics to diagnostics. J Pharm Sci. 2005;94(10):2135–46.

    Article  CAS  PubMed  Google Scholar 

  141. Reubi J. Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev. 2003;24(4):389–427.

    Article  CAS  PubMed  Google Scholar 

  142. Arias JL. Drug targeting strategies in cancer treatment: an overview. Mini Rev Med Chem. 2011;11(1):1–17.

    Article  CAS  PubMed  Google Scholar 

  143. Haubner R, Wester H, Reuning U, et al. Radiolabeled alpha(v)beta(3) integrin antagonists: a new class of tracers for tumor targeting. J Nucl Med. 1999;40(6):1061–71.

    CAS  PubMed  Google Scholar 

  144. Zhan C, Gu B, Xie C, Li J, Liu Y, Lu W. Cyclic RGD conjugated poly(ethylene glycol)-co-poly(lactic acid) micelle enhances paclitaxel anti-glioblastoma effect. J Control Release. 2010;143(1):136–42.

    Article  CAS  PubMed  Google Scholar 

  145. Cornelio DB, Roesler R, Schwartsmann G. Gastrin-releasing peptide receptor as a molecular target in experimental anticancer therapy. Ann Oncol. 2007;18(9):1457–66.

    Article  CAS  PubMed  Google Scholar 

  146. Janib SM, Moses AS, MacKay JA. Imaging and drug delivery using theranostic nanoparticles. Adv Drug Deliv Rev. 2010;62(11):1052–63.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  147. Debbage P, Jaschke W. Molecular imaging with nanoparticles: giant roles for dwarf actors. Histochem Cell Biol. 2008;130(5):845–75.

    Article  CAS  PubMed  Google Scholar 

  148. Choi KY, Jeon EJ, Yoon HY, et al. Theranostic nanoparticles based on PEGylated hyaluronic acid for the diagnosis, therapy and monitoring of colon cancer. Biomaterials. 2012;33(26):6186–93.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  149. Medintz IL, Uyeda HT, Goldman ER, Mattoussi H. Quantum dot bioconjugates for imaging, labelling and sensing. Nat Mater. 2005;4(6):435–46.

    Article  CAS  PubMed  Google Scholar 

  150. Tan WB, Jiang S, Zhang Y. Quantum-dot based nanoparticles for targeted silencing of HER2/neu gene via RNA interference. Biomaterials. 2007;28(8):1565–71.

    Article  CAS  PubMed  Google Scholar 

  151. Derfus A, Chan W, Bhatia S. Probing the cytotoxicity of semiconductor quantum dots. Nano Lett. 2004;4(1):11–8.

    Article  CAS  Google Scholar 

  152. Shilo M, Reuveni T, Motiei M, Popovtzer R. Nanoparticles as computed tomography contrast agents: current status and future perspectives. Nanomedicine. 2012;7(2):257–69.

    Article  CAS  PubMed  Google Scholar 

  153. Liu Y, Ai K, Lu L. Nanoparticulate X-ray computed tomography contrast agents: from design validation to in vivo applications. Acc Chem Res. 2012;45(10):1817–27.

    Article  CAS  PubMed  Google Scholar 

  154. Zhu J, Zheng L, Wen S, et al. Targeted cancer theranostics using alpha-tocopheryl succinate-conjugated multifunctional dendrimer-entrapped gold nanoparticles. Biomaterials. 2014;35(26):7635–46.

    Article  CAS  PubMed  Google Scholar 

  155. Rabin O, Perez J, Grimm J, Wojtkiewicz G, Weissleder R. An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles. Nat Mater. 2006;5(2):118–22.

    Article  CAS  PubMed  Google Scholar 

  156. Zanzonico P. Principles of nuclear medicine imaging: planar, SPECT, PET, multi-modality, and autoradiography systems. Radiat Res. 2012;177(4):349–64.

    Article  CAS  PubMed  Google Scholar 

  157. Pysz MA, Gambhir SS, Willmann JK. Molecular imaging: current status and emerging strategies. Clin Radiol. 2010;65(7):500–16.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  158. Jennings LE, Long NJ. ‘Two is better than one’-probes for dual-modality molecular imaging. Chem Commun. 2009;24:3511–24.

    Article  CAS  Google Scholar 

  159. Kao H, Lin Y, Chen C, et al. Evaluation of EGFR-targeted radioimmuno-gold-nanoparticles as a theranostic agent in a tumor animal model. Bioorg Med Chem Lett. 2013;23(11):3180–5.

    Article  CAS  PubMed  Google Scholar 

  160. Liu Y, Welch MJ. Nanoparticles labeled with positron emitting nuclides: advantages, methods, and applications. Bioconjug Chem. 2012;23(4):671–82.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  161. Gambhir SS. Molecular imaging of cancer with positron emission tomography. Nat Rev Cancer. 2002;2(9):683–93.

    Article  CAS  PubMed  Google Scholar 

  162. Juweid M, Cheson B. Current concepts—positron-emission tomography and assessment of cancer therapy. N Engl J Med. 2006;354(5):496–507.

    Article  CAS  PubMed  Google Scholar 

  163. Chen F, Hong H, Zhang Y, et al. In vivo tumor targeting and image-guided drug delivery with antibody-conjugated, radio labeled mesoporous silica nanoparticles. ACS Nano. 2013;7(10):9027–39.

    Article  CAS  PubMed  Google Scholar 

  164. Wang C, Ravi S, Garapati US, et al. Multifunctional chitosan magnetic-graphene (CMG) nanoparticles: a theranostic platform for tumor-targeted co-delivery of drugs, genes and MRI contrast agents. J Mat Chem B. 2013;1(35):4396–405.

    Article  CAS  Google Scholar 

  165. Kim KS, Park W, Hu J, Bae YH, Na K. A cancer-recognizable MRI contrast agents using pH-responsive polymeric micelle. Biomaterials. 2014;35(1):337–43.

    Article  CAS  PubMed  Google Scholar 

  166. Liu T, Li X, Qian Y, Hu X, Liu S. Multifunctional pH-disintegrable micellar nanoparticles of asymmetrically functionalized beta-cyclodextrin-based star copolymer covalently conjugated with doxorubicin and DOTA-gd moieties. Biomaterials. 2012;33(8):2521–31.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was funded by the National Science Foundation (DMR-0908795) and Cleveland State University through a Faculty Research Development Award and a Cellular and Molecular Medicine Specialization Fellowship (JC).

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The authors declare that no conflict of interest exists.

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  1. Department of Chemical and Biomedical Engineering, Cleveland State University, Cleveland, OH, 44115, USA

    James T. Cole & Nolan B. Holland

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Correspondence to Nolan B. Holland.

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Cole, J.T., Holland, N.B. Multifunctional nanoparticles for use in theranostic applications. Drug Deliv. and Transl. Res. 5, 295–309 (2015). https://doi.org/10.1007/s13346-015-0218-2

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