Safe and Targeted Sonodynamic Cancer Therapy Using Biocompatible Exosome-Based Nanosonosensitizers

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Sonodynamic therapy (SDT) utilizes ultrasound-activated sonosensitizers to generate reactive oxygen species (ROS) for cancer treatment.
• Exosomes offer a biocompatible nanocarrier platform for targeted drug delivery.
• Developing targeted delivery systems for sonosensitizers is crucial for enhancing SDT efficacy and safety.

Purpose of the Study:

• To engineer folic acid-conjugated exosomes (FA-ExoICG) for targeted delivery of indocyanine green (ICG).
• To evaluate the efficacy of FA-ExoICG in enhancing ROS generation and sonodynamic cancer cell killing.
• To assess the in vivo tumor targeting, pharmacokinetic properties, and therapeutic effects of FA-ExoICG in a mouse model.

Main Methods:

• Exosomes were loaded with indocyanine green (ICG) and surface-functionalized with folic acid (FA).
• In vitro studies assessed cellular uptake, ROS generation, and cytotoxicity in breast cancer cells.
• In vivo studies evaluated tumor accumulation, pharmacokinetics, and tumor growth suppression in mice following SDT.

Main Results:

• FA-ExoICG demonstrated enhanced aqueous stability and cellular uptake of ICG compared to free ICG and non-targeted exosomes.
• FA-ExoICG significantly increased ROS generation and sonotoxicity in cancer cells.
• In vivo, FA-ExoICG exhibited superior tumor accumulation and pharmacokinetics, leading to significant tumor growth inhibition without systemic toxicity.

Conclusions:

• Folic acid-conjugated exosomes serve as effective nanocarriers for targeted sonodynamic cancer therapy.
• FA-ExoICG enhances the efficacy of sonodynamic therapy by improving targeted delivery and ROS production.
• This approach shows promise for safe and effective cancer treatment with minimal side effects.