Strategies To Design and Synthesize Polymer-Based Stimuli-Responsive Drug-Delivery Nanosystems

The emergence and development of nanomedicine have alleviated problems existing in traditional chemotherapy drugs, such as short lifetime, concomitant side effects, and weak tumor-targeting capability. Nevertheless, the further applications of drug-loaded nanocarriers are still limited by their premature leakage, weak targeting capability, and insufficient intracellular release. In past decades, various nanocarriers, including gold nanoparticles, porous silica nanoparticles, carbon-based nanoparticles, micelles, liposomes, and polymer-drug conjugates, have been intensively investigated for tumor therapy. Among these, polymer-based nanocarriers have attracted more attention due to their biocompatibilities and capability of being modified for stimuli-responsive drug release. In this review, three popular strategies to design and synthesize polymer-based stimuli-responsive nanocarriers are discussed. The discussion goes from stimuli-responsive polymers with responsive backbones or modified by responsive functional groups for drug encapsulation and release to polymer-drug conjugates with responsive covalent linkages. In particular, due to the facile synthetic processes and mild reaction conditions for crosslinked structures, the latest progress in responsive crosslinked structures is emphasized. Finally, future perspectives for these nanomaterials are given, which are expected to provide inspiration for researchers to design more effective and safer tumor-killing nanomedicines.