Anticancer drug-loaded mesenchymal stem cells for targeted cancer therapy

Area of Science:

• Oncology
• Biotechnology
• Cell Biology

Background:

• Mesenchymal stem cells (MSCs) possess inherent tumor-homing capabilities, making them promising candidates for targeted cancer therapy delivery systems.
• Effective utilization of MSCs requires functionalization with therapeutic agents, such as anti-cancer drugs, without compromising their tumor-targeting properties.

Purpose of the Study:

• To functionalize mesenchymal stem cells (MSCs) with doxorubicin-loaded liposomes (DOX-Lips) using the avidin-biotin complex method.
• To evaluate the drug delivery efficiency and anti-tumor efficacy of these modified MSCs (DOX-Lip-MSCs).

Main Methods:

• Modification of murine mesenchymal stem cells (C3H10T1/2) with doxorubicin-loaded liposomes (DOX-Lips) via the avidin-biotin complex.
• Quantification of doxorubicin (DOX) per cell and assessment of tumor-homing ability.
• In vitro co-culture assays with colon cancer cells (colon26/fluc and colon26/GFP) to evaluate drug transfer and proliferation suppression.
• In vivo studies using subcutaneous and lung metastasis mouse models to assess tumor growth suppression.

Main Results:

• DOX-Lip-MSCs achieved a drug loading of approximately 21.5 pg DOX per cell, with no significant alteration in tumor-homing capacity.
• DOX-Lip-MSCs demonstrated significantly enhanced suppression of colon cancer cell proliferation compared to DOX-Lips alone.
• Evidence of efficient intercellular doxorubicin transfer from modified MSCs to adjacent cancer cells was observed.
• DOX-Lip-MSCs significantly suppressed tumor growth in both subcutaneous and lung metastasis models.

Conclusions:

• Functionalizing MSCs with DOX-Lips is a viable strategy for enhancing targeted cancer therapy.
• The modified MSCs facilitate efficient intercellular drug delivery, leading to potent anti-tumor effects.
• This approach holds promise as an advanced drug delivery system for effective tumor targeting.