Understanding and Overcoming the Acellular Barrier of Breast Tumors for Improving Nanoparticle Mediated Chemotherapy

This project proposes to study the diffusion of NPs in a 3D breast tumor model of varying stiffness associated with cancer progression. Furthermore, it proposes a sequential delivery of collagenase followed by niclosamide (a potential anti-fibrotic agent), using pH responsive NPs. Collagenase is expected to degrade stiff hydrogel (which mimics tumor stroma) and niclosamide is expected to inhibit the deposition of new extra cellular matrix, thus facilitating an improved NP penetration and accumulation into the tumoroid. The improved bioavailability of NP in the tumor is expected to significantly enhance the therapeutic efficacy of traditional chemotherapy. Moreover, the proposed strategy can be used as a platform technology for other solid tumors as well as fibrotic diseases.