Cisplatin (CDDP) is a potent first-line antitumor drug but suffers severe side effects and poor pharmacokinetics. Its complexation with polycarboxylic acids, such as polyglutamic acids, is generally used to fabricate nanoformulations for CDDP delivery; however, the multiple strong complexations makes intracellular drug release slow. Herein, we report a novel polyphenol-metal coordination method to fabricate CDDP-incorporated core-shell nanoparticles, which are stable in blood circulation but dissociate in the tumor. Methoxyl-PEG terminated with one or two gallic acids (PEG-GA or PEG-GA2) complexed CDDP and produced well-defined nanoparticles (PEG-GAx/Pt) with CDDP loading contents as high as 17.7% to 29.8%. The PEG-GAx/Pt nanoparticles were very stable in the physiological conditions and had slow blood clearance and efficient tumor accumulation, but dissociated quickly and released CDDP in response to the tumor acidity or elevated levels of reactive oxygen species (ROS). PEG-GAx/Pt nanoparticles exhibited improved antitumor efficiency against 4 T1 breast cancer and A549 lung carcinoma with much-reduced toxicity compared to free CDDP. The work demonstrates a new strategy of cisplatin-polyphenol coordination for developing platinum drugs' nanomedicines.

顺铂（CDDP）是一种有效的一线抗肿瘤药物，但副作用严重，药代动力学差。它与聚羧酸（例如聚谷氨酸）的络合通常用于制造用于CDDP递送的纳米制剂。然而，多种强复合物使细胞内药物释放缓慢。在本文中，我们报告了一种新型的多酚-金属配位方法，以制备结合了CDDP的核壳纳米粒子，该粒子在血液循环中稳定但在肿瘤中解离。甲氧基-PEG以一种或两种没食子酸（PEG-GA或PEG-GA2）络合的CDDP终止，并产生定义明确的纳米颗粒（PEG-GAx / Pt），其CDDP负载量高达17.7％至29.8％。PEG-GAx / Pt纳米粒子在生理条件下非常稳定，血液清除速度缓慢，并且肿瘤蓄积效率高，但很快解离并响应肿瘤酸度或活性氧（ROS）水平升高释放CDDP。与游离CDDP相比，PEG-GAx / Pt纳米粒子对4 T1乳腺癌和A549肺癌的抗肿瘤功效有所提高，毒性大大降低。这项工作展示了开发铂药物纳米药物的顺铂-多酚配位新策略。