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Synthesis of PEGylated hyaluronic acid for loading dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt) in nanoparticles for cancer treatment

Xiu-Quan Quan ,  Lin Kang ,  Xue-Zhe Yin ,  Zhe-Hu Jin ,  Zhong-Gao Gao

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Citation:  Xiu-Quan Quan, Lin Kang, Xue-Zhe Yin, Zhe-Hu Jin, Zhong-Gao Gao. Synthesis of PEGylated hyaluronic acid for loading dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt) in nanoparticles for cancer treatment[J]. Chinese Chemical Letters, 2015, 26(6): 695-699. doi: 10.1016/j.cclet.2015.04.024 shu

Synthesis of PEGylated hyaluronic acid for loading dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt) in nanoparticles for cancer treatment

    • 通讯作者: Zhong-Gao Gao,
  • 基金项目:

    This study was supported by research grants from the National Natural Science Foundation of China (No. 81373342) (No. 81373342)

    Beijing Natural Science Foundation (Nos. 2141004, 7142114). (Nos. 2141004, 7142114)

摘要: Dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt), a cisplatin (CDDP) analog, has shown lower toxicity than CDDP and no cross-resistance with CDDP in many CDDP-resistant cancers. PEGylated hyaluronan (mPEG-HA) is an mPEG conjugated with hyaluronan biodegradable polymer which is a naturally occurring biopolymer in the interstitium, is primarily cleared by the lymphatic system. mPEGhyaluronan-DACHPt (PEG-HA-Pt) conjugate could circulate long-term in the bloodstream and increase DACHPt concentration in the tumor site and decrease systemic toxicity. mPEG-HA conjugates with the range of 1%-5% substitution were synthesized, and the structures were confirmed by 1H NMR and IR. The particle size of DACHPt incorporated with mPEG-HA was about 86 nm and the loading content and efficiency were about 19% (w/w) and 86%, respectively. The synthesized mPEG-HA with different PEG substitution degrees presented non toxicity, and the cell viability of DACHPt loaded in mPEG-HA nanoparticles increased with increasing doses of DACHPt. DACHPt release from nanoparticles slightly decreased with increasing PEG substitution degree from 1% to 5% at 37 ℃, pH 7.4 PBS solution. The DACHPt loaded inmPEG-HA nanoparticles significantly inhibited the growth of A549 xenografts in nude mice when compared to the DACHPt loaded in HA nanoparticles and the control group after 4 weeks treatment (p < 0.01 compared with control). The body weight change curve shows that the mice weight loss was less than 5% by treating with both DACHPt loaded in mPEG-HA and HA nanoparticles. In conclusion, a novel DACHPt loaded mPEG-HA delivery system was developed with sustained release and increased platinum concentration in the tumor.

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    1. [1] S. Carrick, D. Ghersi, N. Wilcken, J. Simes, Platinum containing regimens for metastatic breast cancer, Cochrane Database Syst. Rev. (2004) CD003374, http://dx.doi.org/10.1002/14651858.CD003374.pub3.[1] S. Carrick, D. Ghersi, N. Wilcken, J. Simes, Platinum containing regimens for metastatic breast cancer, Cochrane Database Syst. Rev. (2004) CD003374, http://dx.doi.org/10.1002/14651858.CD003374.pub3.

    2. [2] G. Chu, Cellular-responses to cisplatin—the roles of DNA-binding proteins and DNA-repair, J. Biol. Chem. 269 (1994) 787-790.[2] G. Chu, Cellular-responses to cisplatin—the roles of DNA-binding proteins and DNA-repair, J. Biol. Chem. 269 (1994) 787-790.

    3. [3] D.C. Ihde, J.L. Mulshine, B.S. Kramer, et al., Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung-cancer, J. Clin. Oncol. 12 (1994) 2022-2034.[3] D.C. Ihde, J.L. Mulshine, B.S. Kramer, et al., Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung-cancer, J. Clin. Oncol. 12 (1994) 2022-2034.

    4. [4] R.P. Perng, Y.M. Chen, M. Lu, et al., Gemcitabine versus the combination of cisplatin and etoposide in patients with inoperable non-small-cell lung cancer in a phase II randomized study, J. Clin. Oncol. 15 (1997) 2097-2102.[4] R.P. Perng, Y.M. Chen, M. Lu, et al., Gemcitabine versus the combination of cisplatin and etoposide in patients with inoperable non-small-cell lung cancer in a phase II randomized study, J. Clin. Oncol. 15 (1997) 2097-2102.

    5. [5] B. Desoize, C. Madoulet, Particular aspects of platinum compounds used at present in cancer treatment, Crit. Rev. Oncol. Hematol. 42 (2002) 317-325.[5] B. Desoize, C. Madoulet, Particular aspects of platinum compounds used at present in cancer treatment, Crit. Rev. Oncol. Hematol. 42 (2002) 317-325.

    6. [6] Y. Kidani, K. Inagaki, M. Iigo, A. Hoshi, K. Kuretani, Antitumor activity of 1,2-diaminocyclohexane-platinum complexes against sarcoma-180 ascites form, J. Med. Chem. 21 (1978) 1315-1318.[6] Y. Kidani, K. Inagaki, M. Iigo, A. Hoshi, K. Kuretani, Antitumor activity of 1,2-diaminocyclohexane-platinum complexes against sarcoma-180 ascites form, J. Med. Chem. 21 (1978) 1315-1318.

    7. [7] H. Cabral, N. Nishiyama, S. Okazaki, H. Koyama, K. Kataoka, Preparation and biological properties of dichloro(1,2-diaminocyclo-hexane) platinum (II)(DACHPt)-loaded polymeric micelles, J. Control. Release 101 (2005) 223-232.[7] H. Cabral, N. Nishiyama, S. Okazaki, H. Koyama, K. Kataoka, Preparation and biological properties of dichloro(1,2-diaminocyclo-hexane) platinum (II)(DACHPt)-loaded polymeric micelles, J. Control. Release 101 (2005) 223-232.

    8. [8] H. Cabral, N. Nishiyama, K. Kataoka, Optimization of (1,2-diamino-cyclohexane)-platinum(II)-loaded polymeric micelles directed to improved tumor targeting and enhanced antitumor activity, J. Control. Release 121 (2007) 146-155.[8] H. Cabral, N. Nishiyama, K. Kataoka, Optimization of (1,2-diamino-cyclohexane)-platinum(II)-loaded polymeric micelles directed to improved tumor targeting and enhanced antitumor activity, J. Control. Release 121 (2007) 146-155.

    9. [9] M. Murakami, H. Cabral, Y. Matsumoto, et al., Improving drug potency and efficacy by nanocarrier-mediated subcellular targeting, Sci. Transl. Med. 3 (2011) 64ra2.[9] M. Murakami, H. Cabral, Y. Matsumoto, et al., Improving drug potency and efficacy by nanocarrier-mediated subcellular targeting, Sci. Transl. Med. 3 (2011) 64ra2.

    10. [10] H. Cabral, Y. Matsumoto, K. Mizuno, et al., Accumulation of sub-100 nmpolymeric micelles in poorly permeable tumours depends on size, Nat. Nanotechnol. 6 (2011) 815-823.[10] H. Cabral, Y. Matsumoto, K. Mizuno, et al., Accumulation of sub-100 nmpolymeric micelles in poorly permeable tumours depends on size, Nat. Nanotechnol. 6 (2011) 815-823.

    11. [11] M. Rafi, H. Cabral, M. Kano, et al., Polymeric micelles incorporating (1,2-diaminocyclohexane) platinum(II) suppress the growth of orthotopic scirrhous gastric tumors and their lymph node metastasis, J. Control. Release 159 (2012) 189-196.[11] M. Rafi, H. Cabral, M. Kano, et al., Polymeric micelles incorporating (1,2-diaminocyclohexane) platinum(II) suppress the growth of orthotopic scirrhous gastric tumors and their lymph node metastasis, J. Control. Release 159 (2012) 189-196.

    12. [12] H. Cabral, M. Murakami, H. Hojo, et al., Targeted therapy of spontaneous murine pancreatic tumors by polymeric micelles prolongs survival and prevents peritoneal metastasis, Proc. Natl. Acad. Sci. U. S. A. 110 (2013) 11397-11402.[12] H. Cabral, M. Murakami, H. Hojo, et al., Targeted therapy of spontaneous murine pancreatic tumors by polymeric micelles prolongs survival and prevents peritoneal metastasis, Proc. Natl. Acad. Sci. U. S. A. 110 (2013) 11397-11402.

    13. [13] S. Deshayes, H. Cabral, T. Ishii, et al., Phenylboronic acid-installed polymeric micelles for targeting sialylated epitopes in solid tumors, J. Am. Chem. Soc. 135 (2013) 15501-15507.[13] S. Deshayes, H. Cabral, T. Ishii, et al., Phenylboronic acid-installed polymeric micelles for targeting sialylated epitopes in solid tumors, J. Am. Chem. Soc. 135 (2013) 15501-15507.

    14. [14] J.R. Fraser, T.C. Laurent, Turnover and metabolism of hyaluronan, Ciba Found. Symp. 143 (1989) 41-53 (discussion 53-59, 281-285).[14] J.R. Fraser, T.C. Laurent, Turnover and metabolism of hyaluronan, Ciba Found. Symp. 143 (1989) 41-53 (discussion 53-59, 281-285).

    15. [15] C.B. Knudson, W. Knudson, Hyaluronan-binding proteins in development, tissue homeostasis, and disease, FASEB J. 7 (1993) 1233-1241.[15] C.B. Knudson, W. Knudson, Hyaluronan-binding proteins in development, tissue homeostasis, and disease, FASEB J. 7 (1993) 1233-1241.

    16. [16] J. Entwistle, C.L. Hall, E.A. Turley, HA receptors: regulators of signaling to the cytoskeleton, J. Cell. Biochem. 61 (1996) 569-577.[16] J. Entwistle, C.L. Hall, E.A. Turley, HA receptors: regulators of signaling to the cytoskeleton, J. Cell. Biochem. 61 (1996) 569-577.

    17. [17] T.C. Laurent, Biochemistry of hyaluronan, Acta Otolaryngol. 442 (1987) 7-24.[17] T.C. Laurent, Biochemistry of hyaluronan, Acta Otolaryngol. 442 (1987) 7-24.

    18. [18] K. Akima, H. Ito, Y. Iwata, et al., Evaluation of antitumor activities of hyaluronate binding antitumor drugs: synthesis, characterization and antitumor activity, J. Drug Target. 4 (1996) 1-9.[18] K. Akima, H. Ito, Y. Iwata, et al., Evaluation of antitumor activities of hyaluronate binding antitumor drugs: synthesis, characterization and antitumor activity, J. Drug Target. 4 (1996) 1-9.

    19. [19] Q. Hua, C.B. Knudson, W.J. Knudson, Internalization of hyaluronan by chondrocytes occurs via receptor mediated endocytosis, J. Cell Sci. 106 (1993) 365-375.[19] Q. Hua, C.B. Knudson, W.J. Knudson, Internalization of hyaluronan by chondrocytes occurs via receptor mediated endocytosis, J. Cell Sci. 106 (1993) 365-375.

    20. [20] V. Mironov, G.D. Prestwich, Fabrication of tubular tissue constructs by centrifugal casting of cells suspended in an in situ crosslinkable hyaluronan-gelatin hydrogel, Biomaterials 26 (2005) 7628-7635.[20] V. Mironov, G.D. Prestwich, Fabrication of tubular tissue constructs by centrifugal casting of cells suspended in an in situ crosslinkable hyaluronan-gelatin hydrogel, Biomaterials 26 (2005) 7628-7635.

    21. [21] M. Kurisawa, H. Uyama, Injectable biodegradable hydrogels composed of hyaluronic acid-tyramine conjugates for drug delivery and tissue engineering, Chem. Commun. 34 (2005) 4312-4314.[21] M. Kurisawa, H. Uyama, Injectable biodegradable hydrogels composed of hyaluronic acid-tyramine conjugates for drug delivery and tissue engineering, Chem. Commun. 34 (2005) 4312-4314.

    22. [22] K. Avgoustakis, A. Beletsi, Z. Panagi, et al., PLGA-mPEG nanoparticles of cisplatin: in vitro nanoparticle degradation, in vivo drug release and in vivo drug residence in blood properties, J. Control. Release 79 (2001) 123-135.[22] K. Avgoustakis, A. Beletsi, Z. Panagi, et al., PLGA-mPEG nanoparticles of cisplatin: in vitro nanoparticle degradation, in vivo drug release and in vivo drug residence in blood properties, J. Control. Release 79 (2001) 123-135.

    23. [23] M.S. Newman, G.T. Colbern, P.K. Working, C. Engbers, M.A. Amantea, Comparative pharmacokinetics, tissue distribution, and therapeutic effectiveness of cisplatin encapsulated in long circulating, pegylated liposomes (SPI-077) in tumor-bearing mice, Cancer Chemother. Pharmacol. 43 (1999) 1-7.[23] M.S. Newman, G.T. Colbern, P.K. Working, C. Engbers, M.A. Amantea, Comparative pharmacokinetics, tissue distribution, and therapeutic effectiveness of cisplatin encapsulated in long circulating, pegylated liposomes (SPI-077) in tumor-bearing mice, Cancer Chemother. Pharmacol. 43 (1999) 1-7.

    24. [24] Y. Ohya, T. Masunaga, T. Baba, T. Ouchi, Synthesis and cytotoxic activity of dextran carrying cis-dichloro (cyclohexanetrans-l-1,2-diamine) platinum(II) complex, J. Biomater. Sci. Polym. Ed. 7 (1996) 1085-1096.[24] Y. Ohya, T. Masunaga, T. Baba, T. Ouchi, Synthesis and cytotoxic activity of dextran carrying cis-dichloro (cyclohexanetrans-l-1,2-diamine) platinum(II) complex, J. Biomater. Sci. Polym. Ed. 7 (1996) 1085-1096.

    25. [25] N. Nishiyama, K. Kataoka, Preparation and characterization of size-controlled polymeric micelle containing cis-dichlorodiamine-platinium(II) in the core, J. Control. Release 74 (2001) 83-94.[25] N. Nishiyama, K. Kataoka, Preparation and characterization of size-controlled polymeric micelle containing cis-dichlorodiamine-platinium(II) in the core, J. Control. Release 74 (2001) 83-94.

    26. [26] N. Nishiyama, S. Okazaki, H. Cabral, et al., Novel cisplatin-incorporated polymeric micelles can eradicate solid tumors in mice, Cancer Res. 63 (2003) 8977-8983.[26] N. Nishiyama, S. Okazaki, H. Cabral, et al., Novel cisplatin-incorporated polymeric micelles can eradicate solid tumors in mice, Cancer Res. 63 (2003) 8977-8983.

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  • 发布日期:  2015-04-19
  • 收稿日期:  2014-11-26
  • 网络出版日期:  2015-03-13
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