MMPs-responsive silk spheres for controlled drug release within tumor microenvironment.

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Cancer Research

Background:

• Silk is a biocompatible and biodegradable material suitable for creating nanospheres.
• The tumor microenvironment (TME) overexpresses matrix metalloproteinases (MMPs), presenting a target for drug delivery.
• Functionalizing silk with specific peptides can yield particles with tailored properties for TME targeting.

Purpose of the Study:

• To develop and evaluate bioengineered spider silk spheres functionalized with MMP-responsive peptides for targeted drug release within the TME.
• To investigate the degradation and drug release profiles of these silk spheres in response to MMP enzymes and cancer cells.

Main Methods:

• Production of soluble bioengineered silks (MS12.2MS1, MS12.9MS1, MS22.9MS2) and corresponding silk spheres.
• Functionalization of silk spheres with MMP-2 or MMP-2/9 responsive peptides.
• Loading of doxorubicin (Dox) into the functionalized silk spheres.
• Analysis of silk sphere degradation and Dox release upon treatment with MMP-2/9 enzymes and in the presence of cancer cells in 2D and 3D spheroid models.

Main Results:

• All functionalized silk spheres showed specific degradation by MMP-2/9.
• MS22.9MS2 nanospheres exhibited the highest degradation and Dox release after enzyme treatment.
• Functionalized spheres degraded and released their payload in the presence of MMP-2/9-releasing cancer cells.
• Controlled degradation and drug release were observed in 2D and 3D cancer models using MS22.9MS2 particles, unlike control MS2 spheres.

Conclusions:

• Bioengineered silk spheres can be functionalized with MMP-responsive peptides for targeted drug delivery.
• The MS22.9MS2 nanosphere formulation demonstrates efficient degradation and controlled doxorubicin release within the tumor microenvironment.
• This silk-based system offers a promising approach for localized cancer therapy by exploiting TME-specific enzyme activity.