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Self-organized nanoparticles based on chitosan-folic acid and dextran succinate-doxorubicin conjugates for drug targeting

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Abstract

Folic acid-decorated self-organized nanoparticles were fabricated to target folate receptor of cancer cells. Doxorubicin (DOX) was conjugated with carboxyl group of dextran backbone using succinic anhydride (DexSU-DOX). DOX-loaded self-organized nanoparticles were prepared by complexation with folic acid-grafted chitosan (ChitoFA) and DexSU-DOX. Nanoparticles in the aqueous environment have spherical shapes with average size less than 100 nm and their sizes were increased by coated with ChitoPEG or ChitoFA. At cell culture study with KB cells, ChitoFA coated nanoparticles (FADex NP) revealed folate-receptor mediated endocytosis to cancer cells and cell viability was significantly changed by folate receptor targeting. Tumor xenograft model of KB cells also showed similar results, i.e. FAdex NP efficiently inhibited growth of tumor compared to the treatment group with blocking of folate receptor. These results indicated that DOX-loaded nanoparticles of FADex NP are promising vehicle for anticancer drug targeting.

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References

  • Akiyoshi, K., S. Kobayashi, S. Shichibe, D. Mix, M. Baudys, S.W. Kim, and J. Sunamoto. 1998. Self-assembled hydrogel nanoparticle of cholesterol-bearing pullulan as a carrier of protein drugs: complexation and stabilization of insulin. Journal of Controlled Release 54: 313–320.

    Article  CAS  PubMed  Google Scholar 

  • Bowman, K., and K.W. Leong. 2006. Chitosan nanoparticles for oral drug and gene delivery. International journal of nanomedicine 1: 117–128.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cabral, H., Y. Matsumoto, K. Mizuno, Q. Chen, M. Murakami, M. Kimura, Y. Terada, M.R. Kano, K. Miyazono, M. Uesaka, N. Nishiyama, and K. Kataoka. 2011. Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nature Nanotechnology 6: 815–823.

    Article  CAS  PubMed  Google Scholar 

  • Cadée, J.A., M.J. van Luyn, L.A. Brouwer, J.A. Plantinga, P.B. van Wachem, C.J. de Groot, W. den Otter, and W.E. Hennink. 2000. In vivo biocompatibility of dextran-based hydrogels. Journal of Biomedical Materials Research 50: 397–404.

    Article  PubMed  Google Scholar 

  • Dosio, F., P. Milla, and L. Cattel. 2010. EC-145, a folate-targeted Vinca alkaloid conjugate for the potential treatment of folate receptor-expressing cancers. Current Opinion in Investigational Drugs 11: 1424–1433.

    CAS  PubMed  Google Scholar 

  • Gref, R., Y. Minamitake, M.T. Peracchia, V. Trubetskoy, V. Torchilin, and R. Langer. 1994. Biodegradable long-circulating polymeric nanospheres. Science 263: 1600–1603.

    Article  CAS  PubMed  Google Scholar 

  • Ichinose, K., N. Tomiyama, M. Nakashima, Y. Ohya, M. Ichikawa, T. Ouchi, and T. Kanematsu. 2000. Antitumor activity of dextran derivatives immobilizing platinum complex (II). Anti-Cancer Drugs 11: 33–38.

    Article  CAS  PubMed  Google Scholar 

  • Janes, K.A., P. Calvo, and M.J. Alonso. 2001. Polysaccharide colloidal particles as delivery systems for macromolecules. Advanced Drug Delivery Reviews 47: 83–97.

    Article  CAS  PubMed  Google Scholar 

  • Jeong, Y.I., S.T. Kim, S.G. Jin, H.H. Ryu, Y.H. Jin, T.Y. Jung, I.Y. Kim, and S. Jung. 2008. Cisplatin-incorporated hyaluronic acid nanoparticles based on ion-complex formation. Journal of Pharmaceutical Sciences 97: 1268–1276.

    Article  CAS  PubMed  Google Scholar 

  • Jeong, Y.I., S.G. Jin, I.Y. Kim, J. Pei, M. Wen, T.Y. Jung, K.S. Moon, and S. Jung. 2010. Doxorubicin-incorporated nanoparticles composed of poly(ethylene glycol)-grafted carboxymethyl chitosan and antitumor activity against glioma cells in vitro. Colloids Surfaces B Biointerfaces 79: 149–155.

    Article  CAS  Google Scholar 

  • Jeong, Y.I., D.H. Kim, C.W. Chung, J.J. Yoo, K.H. Choi, C.H. Kim, S.H. Ha, and D.H. Kang. 2012. Self-assembled nanoparticles of hyaluronic acid/poly(DL-lactide-co-glycolide) block copolymer. Colloids Surfaces B Biointerfaces 90: 28–35.

    Article  CAS  Google Scholar 

  • Jeong, Y.I., K.D. Chung, D.H. Kim, Y.H. Kim, Y.S. Lee, and K.C. Choi. 2013. All-trans retinoic acid-incorporated nanoparticles of deoxycholic acid-conjugated dextran for treatment of CT26 colorectal carcinoma cells. International Journal of Nanomedicine 8: 485–493.

    PubMed Central  PubMed  Google Scholar 

  • Jeong, Y.I., S.H. Kim, T.Y. Jung, I.Y. Kim, S.S. Kang, Y.H. Jin, H.H. Ryu, H.S. Sun, S. Jin, K.K. Kim, K.Y. Ahn, and S. Jung. 2006. Polyion complex micelles composed of all-trans retinoic acid and poly (ethylene glycol)-grafted-chitosan. Journal of Pharmaceutical Sciences 95: 2348–2360.

    Article  CAS  PubMed  Google Scholar 

  • Kumar, M., G. Singh, V. Arora, S. Mewar, U. Sharma, N.R. Jagannathan, S. Sapra, A.K. Dinda, S. Kharbanda, and H. Singh. 2012. Cellular interaction of folic acid conjugated superparamagnetic iron oxide nanoparticles and its use as contrast agent for targeted magnetic imaging of tumor cells. International Journal of Nanomedicine 7: 3503–3516.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee, H.Y., Y.I. Jeong, and K.C. Choi. 2011. Hair dye-incorporated poly-γ-glutamic acid/glycol chitosan nanoparticles based on ion-complex formation. International Journal Nanomedicine 6: 2879–2888.

    CAS  Google Scholar 

  • Lim, S.H., Y.I. Jeong, K.S. Moon, H.H. Ryu, Y.H. Jin, S.G. Jin, T.Y. Jung, I.Y. Kim, S.S. Kang, and S. Jung. 2010. Anticancer activity of PEGylated matrix metalloproteinase cleavable peptide-conjugated adriamycin against malignant glioma cells. International Journal of Pharmaceutics 387: 209–214.

    Article  CAS  PubMed  Google Scholar 

  • Liu, X., W. Cui, B. Li, and Z. Hong. 2012. Targeted therapy for glioma using cyclic RGD-entrapped polyionic complex nanomicelles. International Journal of Nanomedicine 7: 2853–2862.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mbakidi, J.P., N. Drogat, R. Granet, T.S. Ouk, M.H. Ratinaud, E. Rivière, M. Verdier, and V. Sol. 2013. Hydrophilic chlorin-conjugated magnetic nanoparticles–potential anticancer agent for the treatment of melanoma by PDT. Bioorganic & Medicinal Chemistry Letters 23: 2486–2490.

    Article  CAS  Google Scholar 

  • Modi, S., J. Prakash Jain, A.J. Domb, and N. Kumar. 2006. Exploiting EPR in polymer drug conjugate delivery for tumor targeting. Current Pharmaceutical Design 12: 4785–4796.

    Article  CAS  PubMed  Google Scholar 

  • Saito, S., M. Tsugeno, D. Koto, Y. Mori, Y. Yoshioka, S. Nohara, and K. Murase. 2012. Impact of surface coating and particle size on the uptake of small and ultrasmall superparamagnetic iron oxide nanoparticles by macrophages. International Journal of Nanomedicine 7: 5415–5421.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang, W., F. Zhou, L. Ge, X. Liu, and F. Kong. 2012. Transferrin-PEG-PE modified dexamethasone conjugated cationic lipid carrier mediated gene delivery system for tumor-targeted transfection. International Journal of Nanomedicine 7: 2513–2522.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhou, X., M. Zhang, B. Yung, H. Li, C. Zhou, L.J. Lee, and R.J. Lee. 2012. Lactosylated liposomes for targeted delivery of doxorubicin to hepatocellular carcinoma. International Journal of Nanomedicine 7: 5465–5474.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zwicke GL, Mansoori GA, Jeffery CJ. 2012. Utilizing the folate receptor for active targeting of cancer nanotherapeutics. Nano Reviews 3.

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Correspondence to Ki-Choon Choi.

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Lee, K.D., Choi, SH., Kim, D.H. et al. Self-organized nanoparticles based on chitosan-folic acid and dextran succinate-doxorubicin conjugates for drug targeting. Arch. Pharm. Res. 37, 1546–1553 (2014). https://doi.org/10.1007/s12272-014-0489-z

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  • DOI: https://doi.org/10.1007/s12272-014-0489-z

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