Mesenchymal Stem Cell-Based CO₂-Bubble-Generating Liposomes for Targeted and Controlled Chemotherapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Chemotherapy often causes severe toxicity due to non-specific drug distribution.
• Targeted drug delivery systems are crucial for improving cancer treatment efficacy and reducing side effects.

Purpose of the Study:

• To develop an innovative mesenchymal stem cell (MSC)-based drug delivery system for controlled and tumor-targeted doxorubicin (DOX) release.
• To utilize CO2-bubble-generating thermosensitive liposomes (BG-LPs) for localized drug activation under near-infrared (NIR) irradiation.

Main Methods:

• Encapsulation of DOX within BG-LPs and their incorporation into MSCs (MSC-DOX-BG-LPs).
• Leveraging MSCs' inherent tumor-homing ability via CXCR4-CXCL12 signaling for precise targeting.
• Employing NIR irradiation to trigger liposomal destabilization, CO2 bubble generation, and localized DOX release.

Main Results:

• MSC-DOX-BG-LPs demonstrated stability during circulation and controlled drug release upon NIR stimulation.
• In vitro and in vivo studies showed significant inhibition of tumor proliferation and angiogenesis, along with increased apoptosis.
• MSC-mediated delivery enhanced intratumoral drug accumulation compared to passive liposomal carriers.

Conclusions:

• MSC-DOX-BG-LPs represent a promising platform for targeted chemotherapy, combining active tumor targeting with externally controlled drug release.
• This approach has the potential to improve therapeutic outcomes and patient survival in solid tumors.