Hypoxia-Initiated Supramolecular Free Radicals Induce Intracellular Polymerization for Precision Tumor Therapy

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• Controlled release systems for antitumor therapies often cause off-target side effects.
• In situ therapeutic synthesis using biocompatible materials presents a safer alternative.

Purpose of the Study:

• To develop a hypoxia-initiated supramolecular free radical system for intracellular polymerization and targeted cancer therapy.
• To investigate the disruption of 4T1 cells via in situ polymerization.

Main Methods:

• Utilized a 2:1 supramolecular host-guest complex of cucurbit[7]uril (CB[7]) and perylene diimide derivative (PDI) (PDI+2CB[7]).
• Exploited the tumor's hypoxic and reducing environment to generate free radical anions.
• Initiated free radical polymerization of 2-hydroxyethyl methacrylate (HEMA) within 4T1 cells using the PDI+2CB[7] complex.

Main Results:

• The PDI+2CB[7] complex generated stable free radical anions within 4T1 cells.
• In situ polymerization disrupted the cytoskeleton and organelles of 4T1 cells.
• Achieved significant tumor metabolism disruption and a strong antitumor response without systemic toxicity.

Conclusions:

• Stable, endogenous stimulus-induced supramolecular free radicals can trigger intracellular polymerization.
• This approach offers a selective and effective antitumor therapy without conventional chemotherapeutic agents.
• Demonstrated a promising strategy for safer and more precise cancer treatment.