Emerging antitumor applications of extracellularly reengineered polymeric nanocarriers

Recently, polymeric nanocarriers with shielding surfaces, e.g., poly(ethylene glycol) and small molecules, have been widely applied in antitumor drug delivery mainly because of their stealth during blood circulation. However, the shielding shell greatly hinders the tumor penetration, drug release, and cell internalization of the nanocarriers, which leads to unsatisfactory therapeutic efficacy. To integrate the extended blood circulation time and the enhanced drug transmission in one platform, some extracellularly stimuli-mediated shell-sheddable polymeric nanocarriers have been exploited. The systems are stealthy and stable during blood circulation, and as soon as they reach tumor tissue, the shielding matrices are removed, which is triggered by extracellular endogenous stimuli (e.g., pH or enzymes) or exogenous excitations (e.g., light or voltage). This review mainly focuses on recent advances in the designs and emerging antitumor applications of extracellularly reengineered polymeric nanocarriers for directional drug delivery, as well as perspectives for future developments.