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Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers
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Light-Triggered PEGylation/dePEGylation of the Nanocarriers for Enhanced Tumor Penetration

Mengxue Zhou1, Hui Huang1, Dongqing Wang1

  • 1CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics and University of Chinese Academy of Sciences (UCAS) , Chinese Academy of Sciences (CAS) , Beijing 100049 , P.R. China.

Nano Letters
|May 8, 2019
PubMed

Insights

This study introduces a novel light-triggered strategy to enhance anticancer drug delivery. By removing a protective layer (PEGylation) using near-infrared light, nanocarriers better penetrate tumors, improving therapeutic effectiveness.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Drug Delivery

Background:

  • Nanocarrier-based anticancer drugs often show poor tumor penetration and efficacy.
  • PEGylation, while stabilizing nanoparticles, can hinder tumor penetration due to increased size.

Purpose of the Study:

  • To develop a light-triggered strategy for enhanced nanocarrier tumor penetration and anticancer efficacy.
  • To investigate a dual-responsive (NIR/pH) dePEGylation system activating tumor-targeting moieties.

Main Methods:

  • Developed nanocarriers with embedded up-conversion nanoparticles (UCNPs) for NIR to UV-vis conversion.
  • Utilized a cleavable linker for light-induced PEG removal (dePEGylation).
  • Incorporated iRGD peptide for tumor targeting, activated upon dePEGylation.

Main Results:

  • Near-infrared (NIR) light triggered dePEGylation, removing the PEG layer.
  • DePEGylation significantly enhanced vascular extravasation and deep tumor penetration.
  • The stimuli-responsive nanocarriers demonstrated improved drug delivery and enhanced antitumor effects.

Conclusions:

  • Light-triggered dePEGylation is an effective strategy to overcome nanocarrier tumor penetration limitations.
  • Dual-responsive nanocarriers improve targeted drug delivery and therapeutic outcomes in tumors.
  • This approach offers a promising platform for advanced cancer nanotherapeutics.
Keywords:
Near-infraredantitumordrug deliverydrug penetrationphotocleavable

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