Stimuli-responsive drug delivery systems triggered by intracellular or subcellular microenvironments

Drug delivery systems (DDS) triggered by local microenvironment represents the state-of-art of nanome-dicine design, where the triggering hallmarks at intracellular and subcellular levels could be employed to exquisitely recognize the diseased sites, reduce side effects, and expand the therapeutic window by pre-cisely tailoring the drug-release kinetics. Though with impressive progress, the DDS design functioning at microcosmic levels is fully challenging and underexploited. Here, we provide an overview describing the recent advances on stimuli-responsive DDSs triggered by intracellular or subcellular microenvironments. Instead of focusing on the targeting strategies as listed in previous reviews, we herein mainly highlight the concept, design, preparation and applications of stimuli-responsive systems in intracellular models. Hopefully, this review could give useful hints in developing nanoplatforms proceeding at a cellular level.(c) 2023 Elsevier B.V. All rights reserved.