Open AccessPoly (γ, L‐glutamic acid)‐cisplatin bioconjugate exhibits potent antitumor activity with low toxicity: A comparative study with clinically used platinum derivatives
Author(s) -
Feng Zhen,
Lai Yuping,
Ye Haifeng,
Huang Jing,
Xi Xu Guang,
Wu Zirong
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01708.x
Subject(s) - oxaliplatin , cisplatin , carboplatin , in vivo , pharmacology , conjugate , cytotoxicity , ovarian cancer , drug , drug delivery , cancer research , chemotherapy , medicine , chemistry , cancer , in vitro , biochemistry , biology , colorectal cancer , mathematical analysis , microbiology and biotechnology , mathematics , organic chemistry
We have recently synthesized a new platinum derivative, poly (γ, L‐glutamic acid)‐cisplatin conjugate (γ‐PGA‐CDDP), and shown that it displayed remarkable antitumor activity against breast tumor in a mouse model. The purpose of this study is to systematically compare this new drug with three platinum derivatives currently used in the clinic: cisplatin, carboplatin and oxaliplatin. Here, we show that γ‐PGA‐CDDP displays impressive antitumor activity over the current clinically used platinum drugs. More interestingly and more importantly, γ‐PGA‐CDDP conjugate significantly reduces cytotoxicity, mitigates oxidative stress and improves antioxidative capability in vivo . Animals treated with γ‐PGA‐CDDP display the same profile of body weight as the control animals, while the tumors in γ‐PGA‐CDDP‐treated animals are significantly suppressed compared with those treated with carboplatin and oxaliplatin. Our data suggest that γ‐PGA could be used as an effective carrier for drug delivery and that γ‐PGA‐CDDP conjugate may have potential therapeutic applications in human cancers that are sensitive to treatment with CDDP‐based chemotherapy such as ovarian cancer. ( Cancer Sci 2010; 101: 2476–2482)