Poly (γ, L-glutamic acid)-cisplatin bioconjugate exhibits potent antitumor activity with low toxicity: A comparative study with clinically used platinum derivatives

We have recently synthesized a new platinum derivative, poly (gamma, L-glutamic acid)-cisplatin conjugate (gamma-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 gamma-PGA-CDDP displays impressive antitumor activity over the current clinically used platinum drugs. More interestingly and more importantly, gamma-PGA-CDDP conjugate significantly reduces cytotoxicity, mitigates oxidative stress and improves antioxidative capability in vivo. Animals treated with gamma-PGA-CDDP display the same profile of body weight as the control animals, while the tumors in gamma-PGA-CDDP-treated animals are significantly suppressed compared with those treated with carboplatin and oxaliplatin. Our data suggest that gamma-PGA could be used as an effective carrier for drug delivery and that gamma-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).