Light-Triggered PEGylation/dePEGylation of the Nanocarriers for Enhanced Tumor Penetration

Abstract

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.

Smart Porous Core–Shell Cuprous Oxide Nanocatalyst with High Biocompatibility for Acid‐Triggered Chemo/Chemodynamic Synergistic Therapy

“…The above results notified that Cu 2 O-PEG NCs could prominently accumulated in tumor region, which was owing to the external high-density hydrophilic PEG shell for improved passive targeting through high-efficiency enhanced permeability and retention effect. [19,28] Encouraged by the excellent tumor accumulation of Cu 2 O-PEG NCs, the in vivo therapy efficacy of DOX@Cu 2 O-PEG NCs was further evaluated by MCF-7 tumor-bearing mice. As exhibited in Figure 5C,D, the mice treated with DOX alone showed slight tumor growth inhibition effect, while the growth of tumors on mice injected with Cu 2 O-PEG NCs was noticeably controlled, which was ascribed to the effective accumulation and long retention of Cu 2 O-PEG NCs in tumor for CDT compared with nonspecific DOX.…”

Remote Light‐Responsive Nanocarriers for Controlled Drug Delivery: Advances and Perspectives

“…With similar principle, Hu et al developed a light‐triggered PEGylation/dePEGylation strategy, whereby NIR‐/pH‐ dual‐ responsive dePEGylation activates a disulfide‐bridged cyclic peptide, iRGD, for tumor targeting . As shown in Figure , an amphiphilic polymer (PEG–Nbz–PAE–Nbz–PEG, HTMP) containing PEG (as hydrophilic segment) and pH‐sensitive poly(β‐aminoester) (as hydrophobic segment) covalently linked via oNB linker was synthesized.…”

Overcoming Physiological Barriers to Nanoparticle Delivery—Are We There Yet?

“…Shedding of PEG by NIR light was achieved by utilizing a UVsensitive o-nitrobenzyl (Nbz) linker, connecting PEG to poly-βaminoesters (PAE; PEG-Nbz-PAE-NBz-PEG). By incorporation of UCNPs, this setup allowed release of encapsulated doxorubicin in response to NIR illumination, which first led to removal of the PEG layer by the upconverted UV irradiation and also allowed cleavage of the pH sensitive PAE (Zhou et al, 2019).…”