Delivery of Cationic Platinum Prodrugs via Reduction Sensitive Polymer for Improved Chemotherapy. Issue 45 (23rd September 2021)

• Record Type: Journal Article
• Authors: Chen, Hao; Wang, Yushu; Liu, Yulin; Tang, Lin; Mu, Qingchun; Yin, Xiangye; Zheng, Liuchun; Chen, Youbai; Liu, Chaoyong
• Is Part Of: Small. Volume 17:Issue 45(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-09-23
• Subjects: cationic drugs -- phenanthriplatin -- Pt(IV) prodrugs -- reduction sensitive polymers; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202101804
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: A cationic monofunctional platinum anticancer drug, phenanthriplatin (PhenPt(II)), exhibits promising anticancer effect on various cancer cell lines. Unlike the conventional platinum(II) drugs, PhenPt(II) is more likely to bind the N7 adenosine base of DNA in situ, and consequently resulting in a unique cellular response profile and unusual potency. However, since this drug is positively charged, it can easily bind to plasma protein that leads to rapid systematic clearance and deleterious toxicities, which greatly limits its in vivo application. Herein, a lipophilic phenanthriplatin (PhenPt(IV)) prodrug is synthesized. To further reduce its toxicity, a negatively charged polymer P1 with reduction responsiveness is assembled with PhenPt(IV) to form PhenPt(IV) NPs. In comparison to cisplatin, PhenPt(IV) NPs exhibit up to 30 times greater in vitro potency against various cancer cell lines. Additionally, in vivo, no obvious side effect is found on PhenPt(IV) NPs. Significant enhancement in tumor accumulation and improvement of drug efficacy in 4T1 tumor model are demonstrated. Taken together, this study provides a promising strategy for the clinical translation of phenanthriplatin. Abstract : Phenanthriplatin (PhenPt(II)) is the most potent monofunctional platinum complex. However, the severe toxicity greatly limits its in vivo application. In this work, a Pt(IV)‐based nanomedicine is developed via assembling a PhenPt(IV) prodrug with reduction sensitive polymers for reduced side effect and improved therapeutic outcome, offering an effective strategy for the clinical translation of PhenPt(II).