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Therapeutic targeting of chitosan-PEG-folate-complexed oncolytic adenovirus for active and systemic cancer gene

Oh-Joon Kwon1, Eunah Kang, Joung-Woo Choi

  • 1Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|April 9, 2013
PubMed

Insights

This study developed novel Adenovirus (Ad) nanocomplexes coated with chitosan, polyethylene glycol (PEG), and folic acid (FA) for improved systemic cancer therapy. The Ad/chitosan-PEG-FA significantly enhanced tumor targeting and reduced liver toxicity, showing potential for effective cancer treatment.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Adenovirus (Ad)-based cancer therapies face challenges with systemic delivery due to host immune responses, short circulation times, and non-specific liver uptake.
  • Direct tumor injection limits the reach and efficacy of Ad therapies.

Purpose of the Study:

  • To develop a modified Adenovirus (Ad) nanocomplex for enhanced systemic delivery and improved safety and efficacy in cancer therapy.
  • To evaluate the targeting ability, circulation time, immune response, and antitumor efficacy of the modified Ad nanocomplexes.

Main Methods:

  • Oncolytic Adenovirus (Ad) was coated with chitosan and conjugated with polyethylene glycol (PEG) and/or folic acid (FA) to create Ad/chitosan-FA, Ad/chitosan-PEG, and Ad/chitosan-PEG-FA nanocomplexes.
  • In vivo studies in mice assessed blood circulation time, immune response (neutralizing antibodies), biodistribution (tumor vs. liver uptake), liver enzyme levels, and tumor growth inhibition.

Main Results:

  • PEGylation significantly increased Ad nanocomplex circulation time (9.0-fold and 48.9-fold at 24h for Ad/chitosan-PEG and Ad/chitosan-PEG-FA, respectively).
  • Ad/chitosan-PEG-FA showed a 75.3% decrease in Ad-specific neutralizing antibodies and a significantly enhanced tumor-to-liver ratio (285.0-fold increase in tumor, 378-fold reduction in liver).
  • Systemic delivery of Ad/chitosan-PEG-FA significantly inhibited FR-positive tumor growth (52.8% decrease) and completely eliminated Ad-related liver damage, with no elevation in liver enzymes.

Conclusions:

  • Conjugation of chitosan-PEG-FA to oncolytic Ad significantly improves antitumor efficacy and safety profiles for systemic administration.
  • Ad/chitosan-PEG-FA demonstrates potential as a therapeutic agent for targeting folate receptor-positive cancers via systemic delivery.

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