Emerging platinum(IV) prodrug nanotherapeutics: A new epoch for platinum-based cancer therapy

Shunzhe Zheng, Guanting Li, Jianbin Shi, Xinying Liu, Meng Li, Zhonggui He, Chutong Tian, Ken ichiro Kamei

Research output: Contribution to journalReview articlepeer-review

Abstract

Owing to the unique DNA damaging cytotoxicity, platinum (Pt)-based chemotherapy has long been the first-line choice for clinical oncology. Unfortunately, Pt drugs are restricted by the severe dose-dependent toxicity and drug resistance. Correspondingly, Pt(IV) prodrugs are developed with the aim to improve the antitumor performance of Pt drugs. However, as “free” molecules, Pt(IV) prodrugs are still subject to unsatisfactory in vivo destiny and antitumor efficacy. Recently, Pt(IV) prodrug nanotherapeutics, inheriting both the merits of Pt(IV) prodrugs and nanotherapeutics, have emerged and demonstrated the promise to address the underexploited dilemma of Pt-based cancer therapy. Herein, we summarize the latest fronts of emerging Pt(IV) prodrug nanotherapeutics. First, the basic outlines of Pt(IV) prodrug nanotherapeutics are overviewed. Afterwards, how versatile Pt(IV) prodrug nanotherapeutics overcome the multiple biological barriers of antitumor drug delivery is introduced in detail. Moreover, advanced combination therapies based on multimodal Pt(IV) prodrug nanotherapeutics are discussed with special emphasis on the synergistic mechanisms. Finally, prospects and challenges of Pt(IV) prodrug nanotherapeutics for future clinical translation are spotlighted.

Original languageEnglish (US)
Pages (from-to)819-846
Number of pages28
JournalJournal of Controlled Release
Volume361
DOIs
StatePublished - Sep 2023

Keywords

  • Cancer therapy
  • Combination therapy
  • Platinum drug
  • Platinum(IV) prodrug
  • Prodrug nanotherapeutics

ASJC Scopus subject areas

  • Pharmaceutical Science

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