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Session: Technical Session IV

Nanomedicine and Nanoscale Delivery IV

Wednesday, July 10, 2024
2:30 PM – 4:30 PM CET
Location: Sala Europa
Abnormalities in tumor vasculature and the dense extracellular matrix within the tumor microenvironment (TME) impede drug delivery, compromising therapeutic outcomes. Here, we have developed a polymeric formulation containing pirfenidone, which has been successful to restore the TME in breast and sarcoma tumors. We investigated in vivo the ability of micellar formulation to induce similar mechanotherapeutics effects to tumors with a 100-fold lower dose than the free pirfenidone. Importantly, combination of pirfenidone-loaded micelles with immune checkpoint inhibition significantly delayed primary tumor growth, leading to a significant improvement in overall survival and in complete cure for the breast tumor model. Furthermore, the combination treatment increased CD4+ and CD8+ T cell infiltration and suppressed myeloid derived suppressor cells, creating favorable immuno-stimulatory conditions, which led to immunological memory. Ultrasound shear wave elastography (SWE) was able to monitor changes in tumor stiffness during treatment, suggesting optimal treatment conditions. Micellar encapsulation is a promising strategy for mechanotherapeutics and imaging methods, such as SWE, can assist their clinical translation.