Coating nanosized anticancer drug delivery systems (DDSs) with poly(ethylene glycol) (PEG), the so-called PEGylation, has been proven an effective method to enhance hydrophilicity, aqueous dispersivity, and stability of DDSs. What is more, as PEG has the lowest level of protein absorption of any known polymer, PEGylation can reduce the clearance of DDSs by the mononuclear phagocyte system (MPS) and prolong their blood circulation time in vivo. However, the "stealthy" characteristic of PEG also diminishes the uptake of DDSs by cancer cells, which may reduce drug utilization. Therefore, dynamic protection strategies have been widely researched in the past years. Coating DDSs with PEG through dynamic covalent or noncovalent bonds that are stable in blood and normal tissues, but can be broken in the tumor microenvironment (TME), can achieve a DePEGylation-based "tumor-triggered" targeting or intracellular drug release, which can effectively improve the utilization of drugs and reduce their side effects. In this review, the stimuli and methods of "tumor-triggered" targeting or intracellular drug release, based on DePEGylation, are summarized. Additionally, the targeting and intracellular controlled release behaviors of the DDSs are briefly introduced.
Keywords: DePEGylationg; controlled release; dynamic protection strategy; tumor-triggered targeting.