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Accelerated DOX release from L-histidine-based polymeric micelles triggered by an early endosomal pH of 6.0 was achieved by pH-sensitive micelles

Doxorubicin-loaded polymeric micelle overcomes multidrug resistance of cancer by double-targeting folate receptor and early endosomal pH.

SMALL, no. 11 (2008): 2043-2050

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摘要

An optimized, pH-sensitive mixed-micelle system conjugated with folic acid is prepared in order to challenge multidrug resistance (MDR) in cancers. The micelles are composed of poly(histidine (His)-co-phenylalanine (Phe))-b-poly(ethylene glycol) (PEG) and poly(L-lactic acid) (PLLA)-b-PEG-folate. Core-forming, pH-sensitive hydrophobic bloc...更多

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简介
  • One of the major challenges in successful cancer chemotherapy is to overcome intrinsic or acquired multidrug resistance (MDR) in tumors.[1,2,3,4,5] MDR mechanisms are associated with a number of efflux pumps including P-glycoprotein (Pgp)[6,7,8,9] and multidrug-resistant protein (MRP),[10] altered expression of antiapoptotic protein Bcl-2[11] and tumor suppressor protein p53,[12] changes in topoisomerase II activity,[13] modifications in glutathione S-transferase,[14] and others.
  • In an effort to reverse MDR, Pgp. Other approaches using poly(ethylene oxide)-b-poly(ecaprolactone) nanoparticles[25] and polymeric nonionic surfactants such as Pluronics[26] and poly(alkylcyanoacrylate) nanoparticles[27] have been studied to overcome MDR.
  • Resistant cancer cells eventually die upon exposure to 10- to 100-fold-higher drug concentrations than would kill sensitive counterparts,[32,33,34] yielding to the hypothesis that there may be a limit for cells to defend themselves against cytotoxic chemicals by various MDR mechanisms
重点内容
  • One of the major challenges in successful cancer chemotherapy is to overcome intrinsic or acquired multidrug resistance (MDR) in tumors.[1,2,3,4,5] MDR mechanisms are associated with a number of efflux pumps including P-glycoprotein (Pgp)[6,7,8,9] and multidrug-resistant protein (MRP),[10] altered expression of antiapoptotic protein Bcl-2[11] and tumor suppressor protein p53,[12] changes in topoisomerase II activity,[13] modifications in glutathione S-transferase,[14] and others
  • Because the resistance of clinical tumors is not often explained by Pgp overexpression, various other mechanisms associated with multicellular events, soluble factors, and cellular adhesion have been proposed for clinically relevant MDR.[28,29,30]
  • Most living organisms, including bacteria and healthy organs in the body, share common MDR mechanisms expressed by cancer cells
  • Accelerated DOX release from L-histidine-based polymeric micelles triggered by an early endosomal pH of 6.0 was achieved by pH-sensitive micelles
  • The micelle core was composed of histidine/phenylalanine (16 mol%) copolymer (80 wt%) and poly(L-lactic acid) (20 wt%)
  • This composition was obtained by optimization of the micelle properties in the presence of %20 wt% DOX. When this triggered release was combined with active targeting via folate receptor-mediated endocytosis, this nanosystem was able to effectively kill drugsensitive ovarian cancer cells as well as drug-resistant counterpart cells
结果
  • It is known that when monomers with ionizable groups are polymerized, or attached to a polymer, the pK values are shifted.[44] The apparent pKb values of PHP(10), PHP(16), PHP(22), and PHP(27), estimated from Polymer.
  • A hydrophobic environment is known to lower the local dielectric constant and to weaken the ionization tendency of an ionizable group.[45,46] The copolymerization with Phe shifts the pKb of the imidazole group in the His residue to a lower pH.
结论
  • Accelerated DOX release from L-histidine-based polymeric micelles triggered by an early endosomal pH of 6.0 was achieved by pH-sensitive micelles.
  • The micelle core was composed of histidine/phenylalanine (16 mol%) copolymer (80 wt%) and poly(L-lactic acid) (20 wt%).
  • This composition was obtained by optimization of the micelle properties in the presence of %20 wt% DOX.
  • When this triggered release was combined with active targeting via folate receptor-mediated endocytosis, this nanosystem was able to effectively kill drugsensitive ovarian cancer cells as well as drug-resistant counterpart cells.
表格
  • Table1: Characterization of poly(Histidine-co-phenylalanine)
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基金
  • This work was supported by NIH CA101850. [1] G
引用论文
  • [18] M. M. Gottesman, I. Pastan, S. V. Ambudkar, Curr. Opin. Genet. Dev. 1996, 6, 610–617.
    Google ScholarFindings
  • [19] M. Tomonaga, M. Oka, F. Narasaki, M. Fukuda, R. Nakano, H. Takatani, K. Ikeda, K. Terashi, I. Matsuo, H. Soda, K. H. Cowan, S. Kohno, Jpn. J. Cancer Res. 1996, 87, 1263–1270.
    Google ScholarLocate open access versionFindings
  • [20] F. Narasaki, I. Matsuo, N. Ikuno, M. Fukuda, H. Soda, M. Oka, Anticancer Res. 1996, 16, 2079–2082.
    Google ScholarLocate open access versionFindings
  • [21] P. F. Juranka, R. L. Zastawny, V. Ling, FASEB J. 1989, 3, 2583–2592.
    Google ScholarFindings
  • [22] S. P. Cole, R. G. Deeley, Bioessays 1998, 20, 931–940.
    Google ScholarFindings
  • [23] J. Renes, E. G. de Vries, P. L. Jansen, M. Muller, Drug Resist. Update 2000, 3, 289–302.
    Google ScholarLocate open access versionFindings
  • [24] B. I. Sikic, J. Clin. Oncol. 1993, 11, 1629–1635.
    Google ScholarFindings
  • [25] T. Skovsgaard, D. Nielsen, C. H. Maare, K. Wassermann, Int. Rev. Cytol. 1994, 156, 77–157.
    Google ScholarLocate open access versionFindings
  • [26] G. A. Fisher, B. I. Sikic, Hematol. Oncol. Clin. North Am. 1995, 9, 363–382.
    Google ScholarLocate open access versionFindings
  • [27] C. Mamot, D. C. Drummond, K. Hong, D. B. Kirpotin, J. W. Park, Drug Resist. Update 2003, 6, 271–279.
    Google ScholarLocate open access versionFindings
  • [28] J. Huwyler, A. Cerletti, G. Fricker, A. N. Eberle, J. Drewe, J. Drug Targeting 2002, 10, 73–79.
    Google ScholarLocate open access versionFindings
  • [29] C. E. Soma, C. Dubernet, D. Bentolila, S. Benita, P. Couvreur, Biomaterials 2000, 21, 1–7.
    Google ScholarLocate open access versionFindings
  • [30] S. C. J. Steiniger, J. Kreuter, A. S. Khalansky, I. N. Skidan, A. I. Bobruskin, Z. S. Smirnova, S. E. Severin, R. Uhl, M. Kock, K. D. Geiger, S. E. Gelperina, Int. J. Cancer 2004, 109, 759–767.
    Google ScholarLocate open access versionFindings
  • [31] Z. Liu, X. Y. Wu, R. Bendayan, J. Pharm. Sci. 1999, 88, 412–418.
    Google ScholarLocate open access versionFindings
  • [32] R. Cheung, Y. Ying, A. M. Rauth, N. Marcon, X. Y. Wu, Biomaterials 2005, 26, 5375–5385.
    Google ScholarLocate open access versionFindings
  • [33] A. C. Verdierede, C. Dubernet, F. Nemati, E. Soma, M. Appel, J. Ferte, S. Bernard, F. Puisieux, P. Couvreur, Br. J. Cancer 1997, 76, 198–205.
    Google ScholarLocate open access versionFindings
  • [34] A. V. Kabanov, E. V. Batrakova, V. Y. Alakhov, Adv. Drug. Deliv. Rev. 2002, 54, 759–779.
    Google ScholarLocate open access versionFindings
  • [35] A. Gabizon, R. Catane, B. Uziely, Cancer Res. 1994, 54, 987–992.
    Google ScholarFindings
  • [36] G. Storm, M. T. ten Kate, P. K. Working, I. A. Bakker-Woudenberg, Clin. Cancer Res. 1998, 4, 111–115.
    Google ScholarLocate open access versionFindings
  • [37] A. R. Thierry, D. Vige, S. S. Coughlin, J. A. Belli, A. Dritschilo, A. Rahman, FASEB J. 1993, 7, 572–579.
    Google ScholarFindings
  • [38] F. Nemati, C. Dubernet, H. Fessi, A. Colin de Verdiere, M. F. Poupon, F. Puisieux, P. Couvreur, Int. J. Pharm. 1996, 138, 237–246.
    Google ScholarLocate open access versionFindings
  • [39] R. H. Muller, K. Mader, S. Gohla, Eur. J. Pharm. Biopharm. 2000, 50, 161–177.
    Google ScholarLocate open access versionFindings
  • [40] R. H. Muller, D. Ruhl, S. Runge, K. Schulze-Forster, W. Mehnert, Pharm. Res. 1997, 14, 458–462.
    Google ScholarLocate open access versionFindings
  • [41] S. M. Hahn, A. Russo, J. A. Cook, J. B. Mitchell, Int. J. Oncol 1999, 14, 273–279.
    Google ScholarLocate open access versionFindings
  • [42] E. S. Lee, K. Na, Y. H. Bae, J. Controlled Release 2003, 91, 103–113.
    Google ScholarLocate open access versionFindings
  • [43] R. Duncan, Pharm. Sci. Technol. Today 1999, 2, 441–449.
    Google ScholarLocate open access versionFindings
  • [44] G. Mohajer, E. S. Lee, Y. H. Bae, Pharm. Res. 2007, 24, 1618–1627.
    Google ScholarLocate open access versionFindings
  • [45] J. M. Benns, J. S. Choi, R. I. Mahato, J. S. Park, S. W. Kim, Bioconjug. Chem. 2000, 11, 637–645.
    Google ScholarLocate open access versionFindings
  • [46] D. Putnam, C. A. Gentry, D. W. Pack, R. Langer, Proc. Natl. Acad. Sci. USA 2001, 98, 1200–1205.
    Google ScholarLocate open access versionFindings
  • [47] K. Prompruk, T. Govender, S. Zhang, C. D. Xiong, S. Stolnik, Int. J. Pharm. 2005, 297, 242–253.
    Google ScholarLocate open access versionFindings
  • [48] H. Yin, E. S. Lee, D. Kim, K. H. Lee, K. T. Oh, Y. H. Bae, J. Controlled Release 2008, 126, 130–138.
    Google ScholarLocate open access versionFindings
  • [49] D. Suton, S. Wang, N. Nasongkla, J. Gao, E. E. Dormidontova, Exp. Biol. Med. 2007, 232, 1090–1099.
    Google ScholarLocate open access versionFindings
  • [50] N. Raghunand, B. P. Mahoney, R. J. Gillies, Biochem. Pharmacol. 2003, 66, 1219–1229.
    Google ScholarLocate open access versionFindings
  • [51] I. G. Gampbell, T. A. Jones, W. D. Foulkers, J. Trowsdale, Cancer Res. 1991, 51, 5329–5338.
    Google ScholarLocate open access versionFindings
  • [52] M. Pizzato, E. D. Blair, M. Fling, J. Kopf, A. Tomassetti, R. A. Weiss, Y. Takeuchi, Gene Therapy 2001, 8, 1088–1096.
    Google ScholarLocate open access versionFindings
  • [53] Z. G. Gao, D. H. Lee, D. I. Kim, Y. H. Bae, J. Drug Targeting 2005, 13, 391–397.
    Google ScholarLocate open access versionFindings
  • [54] S. M. Simon, M. Schindler, Proc. Natl. Acad. Sci. USA 1994, 91, 3497–3504.
    Google ScholarLocate open access versionFindings
  • [55] S. K. Han, K. Na, Y. H. Bae, Colloids Surf. A. Physicochem. Eng. Aspects 2003, 214, 49–59.
    Google ScholarLocate open access versionFindings
  • Revised: June 15, 2008
    Google ScholarFindings
  • 2050 www.small-journal.com ß 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim small 2008, 4, No. 11, 2043–2050
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