Stromal disruption facilitating invasion of a 'nano-arsenal' into the solid tumor

Owing to the indispensable role of nanotechnology in cancer therapy, it is imperative to comprehend every aspect limiting its therapeutic potential. Several preclinical reports have demonstrated the enhanced permeability and retention (EPR)-mediated preferential tumor uptake of nanoparticles. However, the therapeutic outcome of nanotherapeutics is severely compromised by heterogeneous drug distribution and insufficient penetration of nanomedicine in a solid tumor owing to the dense tumor extracellular matrix (ECM). Herein, we elaborate on various preclinically investigated tumor stromal disrupting strategies, which we call 'cannons', to compromise the impenetrable 'fortress-like' solid tumor microenvironment. We have described and summarized major approaches to enhance the penetration of a 'nano-arsenal' in solid tumors. ECM remodeling strategies could be very beneficial in enhancing the therapeutic efficacy of monoclonal antibodies and translational nanomedicine.