Nanocarriers-derived anticancer therapeutics typically suffers from poor tumor penetration and suboptimal antitumor efficacy. Although PEGylation improves the stability of nanoparticles and prolongs drug circulation, it further increases the size of nanoparticles and adversely affects the tumor penetration. Here, we developed a light-triggered PEGylation/dePEGylation strategy, whereby near-infrared (NIR)-/pH- dual responsive dePEGylation activates iRGD for tumor targeting. The embedded up-conversion nanoparticles (UCNPs) could efficiently convert NIR to UV-vis which cleaved the linker to remove PEG. NIR-induced dePEGylation remarkably improved vascular extravasation of drugs and deep tumor penetration. Therefore, the stimuli-responsive nanocarriers facilitated the tumor-targeted delivery of drugs through blood circulation and enhanced the antitumor effects.
Keywords: Near-infrared; antitumor; drug delivery; drug penetration; photocleavable.