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The preparation and characterization of micelles from poly(γ-glutamic acid)-graft-poly(l-lactide) and the cellular uptake thereof

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Abstract

Chemotherapy is a traditional therapeutic approach for the treatment of many solid tumors, but the poor solubility and low bioavailability of hydrophobic anti-cancer drugs greatly limit their applications. In this article, DOX-loaded micelles were fabricated based on an amphiphilic graft polymer composed of hydrophilic poly(γ-glutamic acid) (γ-PGA) and hydrophobic poly (l-lactide) (PLLA). The structure of the copolymers and the characteristic of the micelles were studied. The release profiles of doxorubicin as a model drug from the micelles were measured. Due to the protonation of the amino group of DOX and the conformational alteration of γ-PGA, the release of DOX from γ-PGA-g-PLLA micelle was faster in the acid condition, which is beneficial to tumor therapy. The cellular uptake of the DOX-loaded γ-PGA-g-PLLA micelle was proved to be a GGT-mediated process.

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References

  1. Peer D, Karp JM, Hong S, et al. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2007;2:751–60.

    Article  Google Scholar 

  2. 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;46:6387–92.

    Google Scholar 

  3. Zhong Y, Meng F, Deng C, et al. Ligand-directed active tumor-targeting polymeric nanoparticles for cancer chemotherapy. Biomacromolecules. 2014;15:1955–69.

    Article  Google Scholar 

  4. Wang X, Li S, Shi Y, et al. The development of site-specific drug delivery nanocarriers based on receptor mediation. J Control Release. 2014;193:139–53.

    Article  Google Scholar 

  5. Barouki R, Finidori J, Chobert M, et al. Biosynthesis and processing of gamma-glutamyl transpeptidase in hepatoma tissue culture cells. J Biol Chem. 1984;259:7970–4.

    Google Scholar 

  6. Pompella A, De Tata V, Paolicchi A, et al. Expression of γ-glutamyl transferase in cancer cells and its significance in drug resistance. Biochem Pharmacol. 2006;71:231–8.

    Article  Google Scholar 

  7. Yao D, Jiang D, Huang Z, et al. Abnormal expression of hepatoma specific γ-glutamyl transferase and alteration of γ-glutamyl transferase gene methylation status in patients with hepatocellular carcinoma. Cancer. 2000;88:761–9.

    Article  Google Scholar 

  8. Liao ZX, Peng SF, Ho YC, et al. Mechanistic study of transfection of chitosan/DNA complexes coated by anionic poly (γ-glutamic acid). Biomaterials. 2012;33:3306–15.

    Article  Google Scholar 

  9. Peng SF, Tseng MT, Ho YC, et al. Mechanisms of cellular uptake and intracellular trafficking with chitosan/DNA/poly (γ-glutamic acid) complexes as a gene delivery vector. Biomaterials. 2011;32:239–48.

    Article  Google Scholar 

  10. Peng SF, Yang MJ, Su CJ, et al. Effects of incorporation of poly (γ-glutamic acid) in chitosan/DNA complex nanoparticles on cellular uptake and transfection efficiency. Biomaterials. 2009;30:1797–808.

    Article  Google Scholar 

  11. Kurosaki T, Kitahara T, Fumoto S, et al. Ternary complexes of pDNA, polyethylenimine, and γ-polyglutamic acid for gene delivery systems. Biomaterials. 2009;30:2846–53.

    Article  Google Scholar 

  12. Chang KY, Cheng LW, Ho GH, et al. Fabrication and characterization of poly(γ-glutamic acid)-graft-chondroitin sulfate/polycaprolactone porous scaffolds for cartilage tissue engineering. Acta Biomater. 2009;5:1937–47.

    Article  Google Scholar 

  13. Zeng Wen HuWK, Hao Li, et al. Preparation and characterization of poly (γ-glutamic acid) hydrogels as potential tissue engineering scaffolds. Chin J Polym Sci. 2014;32:1507–14.

    Article  Google Scholar 

  14. Wang X, Uto T, Akagi T, et al. Poly (γ-glutamic acid) nanoparticles as an efficient antigen delivery and adjuvant system: potential for an aids vaccine. J Med Virol. 2008;80:11–9.

    Article  Google Scholar 

  15. Mi FL, Wu YY, Lin YH, et al. Oral delivery of peptide drugs using nanoparticles self-assembled by poly (γ-glutamic acid) and a chitosan derivative functionalized by trimethylation. Bioconjug Chem. 2008;19:1248–55.

    Article  Google Scholar 

  16. Akao T, Kimura T, Hirofuji Y, et al. A poly (γ-glutamic acid)-amphiphile complex as a novel nanovehicle for drug delivery system. J Drug Target. 2010;18:550–6.

    Article  Google Scholar 

  17. Shen HY, Akagi T, Akashi M. Polyampholyte nanoparticles prepared by self-complexation of cationized poly (γ-glutamic acid) for protein carriers. Macromol Biosci. 2012;12:1100–5.

    Article  Google Scholar 

  18. Shima F, Shudo M, Akagi T, et al. Preparation of siRNA carrier based on boronic acid functionalized amphiphilic poly (γ-glutamic acid) nanoparticles. Chem Lett. 2014;43:840–2.

    Article  Google Scholar 

  19. Zhu Y, Akagi T, Akashi M. Preparation and characterization of nanoparticles formed through stereocomplexation between enantiomeric poly (γ-glutamic acid)-graft-poly (lactide) copolymers. Polym J. 2013;45:560–6.

    Article  Google Scholar 

  20. Han L, Hiratake J, Kamiyama A, et al. Design, synthesis, and evaluation of γ-phosphono diester analogues of glutamate as highly potent inhibitors and active site probes of γ-glutamyl transpeptidase. Biochemistry. 2007;46:1432–47.

    Article  Google Scholar 

  21. Ouchi T, Uchida T, Arimura H, et al. Synthesis of poly (l-lactide) end-capped with lactose residue. Biomacromolecules. 2003;4:477–80.

    Article  Google Scholar 

  22. Zhao CL, Winnik MA, Riess G, et al. Fluorescence probe techniques used to study micelle formation in water-soluble block copolymers. Langmuir. 1990;6:514–6.

    Article  Google Scholar 

  23. Moyano DF, Saha K, Prakash G, et al. Fabrication of corona-free nanoparticles with tunable hydrophobicity. ACS Nano. 2014;8:6748–55.

    Article  Google Scholar 

  24. Sun Y, Zou W, Bian S, et al. Bioreducible PAA-g-PEG graft micelles with high doxorubicin loading for targeted antitumor effect against mouse breast carcinoma. Biomaterials. 2013;34:6818–28.

    Article  Google Scholar 

  25. Maeda H, Matsumura Y. Tumoritropic and lymphotropic principles of macromolecular drugs. Crit Rev Ther Drug Carrier Syst. 1988;6:193–210.

    Google Scholar 

  26. Righetti PG, Menozzi M, Gianazza E, et al. Protolytic equilibria of doxorubicin as determined by isoelectric focusing and ‘electrophoretic titration curves’. FEBS Lett. 1979;101:51–5.

    Article  Google Scholar 

  27. Checot F, Lecommandoux S, Gnanou Y, et al. Water-soluble stimuli-responsive vesicles from peptide-based diblock copolymers. Angew Chem Int Ed. 2002;41:1339–43.

    Article  Google Scholar 

  28. Ho GH, Ho TI, Hsieh KH, et al. γ-Polyglutamic acid produced by Bacillus subtilis (natto): structural characteristics, chemical properties and biological functionalities. J Chin Chem Soc. 2006;53:1363–84.

    Article  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (Grant Nos. 51373130, 21004080), the Program for New Century Excellent Talents in Universities (Grant No. NCET-09-0818) of the Ministry of Education of China, the Science and Technology Planning Project of Guangdong Province (Grant No. 2011A060901013), the Guangdong Innovative Research Team Program (Grant No. 2009010057), and the Program for Industry, University & Research Institute Collaboration of Guangdong Province (Grant No. 2012B091100452).

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Correspondence to Yihua Yin or Chao Zhang.

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Liu, M., Huang, G., Cong, Y. et al. The preparation and characterization of micelles from poly(γ-glutamic acid)-graft-poly(l-lactide) and the cellular uptake thereof. J Mater Sci: Mater Med 26, 187 (2015). https://doi.org/10.1007/s10856-015-5519-y

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  • DOI: https://doi.org/10.1007/s10856-015-5519-y

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