Advances in the Research on Intelligent Responsive Prodrug Nano-assembly in Tumor Redox Microenvironment

With the in-depth research and extensive application of biomedical nanotechnology in the field of drug delivery, various nanodrug delivery systems(nano-DDS) have been designed and constructed for the efficient delivery of anticancer drugs.Among them, prodrug-based nanoassemblies, which integrate prodrug strategy and biomedical nanotechnology into one nanosystem, have gradually become an important branch of nano-DDS.The key to the rational design of prodrug-based nanoassemblies lies in the structural modifications of drugs as well as the selective and efficient activation of prodrugs at the target sites.Recently, smart tumor microenvironment stimuliresponsive prodrug-nanosystems have become an important nanoplatform for the research on cancer diagnosis and treatment due to the selective and rapid drug release at tumor sites.This article provides an overview of the recent trends in smart redox-responsive prodrugnanosystems for cancer therapy.Tumor redox microenvironment and redox-responsive chemical linkages are introduced;several redoxresponsive self-assembled nanosystems of polymeric macromolecular prodrugs and small-molecule prodrugs are presented;and the advantages and challenges of the prodrug-based nanoassemblies and the clinical transformation prospects of nano-DDS are highlighted.This review aims to provide reference for the design and construction of tumor stimuli-responsive prodrug-nanosystems.