Glycoengineered mesenchymal stem cells as an enabling platform for two-step targeting of solid tumors

Area of Science:

• Biomedical Engineering
• Oncology
• Stem Cell Biology

Background:

• Current tumor-targeted therapies lack specificity, leading to off-target effects.
• Mesenchymal stem cells (MSCs) possess inherent tumor-homing capabilities.
• Developing strategies to enhance the precision of drug and diagnostic delivery to tumors is crucial.

Purpose of the Study:

• To develop and evaluate a novel two-step tumor targeting strategy utilizing glycoengineered MSCs.
• To assess the efficacy of this strategy in improving the tumor accumulation of diagnostic agents and therapeutic drugs.
• To investigate the potential of this approach for enhancing cancer treatment outcomes.

Main Methods:

• Glycoengineering of MSCs to display azide groups on their surface via non-natural sugar incorporation.
• Utilizing bio-orthogonal copper-free click chemistry for targeted delivery of DBCO-labeled agents to MSC-decorated tumors.
• Evaluating tumor homing, agent accumulation, tumor growth inhibition, and survival in preclinical cancer models (lung, ovarian).

Main Results:

• Glycoengineered MSCs exhibited efficient tumor homing in vivo without compromising viability.
• Subsequent administration of DBCO-labeled agents led to significantly enhanced tumor accumulation.
• Combination therapy with glycoengineered MSCs and paclitaxel-loaded nanoparticles demonstrated significant tumor growth inhibition and improved survival in ovarian cancer models.

Conclusions:

• MSC-based two-step targeting strategy effectively enhances tumor specificity for diagnostic and therapeutic agents.
• This approach holds promise for improving cancer treatment efficacy and patient outcomes.
• Further development could lead to more precise and effective cancer therapies.