Nanomedicine approaches to democratize biotherapies

Biotherapies—including cell and gene therapies, mRNA vaccines, and extracellular vesicles—rely on biological components to target and treat disease. Today, about 59% of therapeutic candidates in development worldwide fall within the scope of biotherapy. Yet major challenges must still be addressed to democratize their use and ensure broad patient access, including high bioproduction costs and complexity, safety considerations, and the physical and biological barriers encountered in vivo. I will discuss how nanomedicine and physics-driven strategies can contribute to overcoming these limitations and expanding the reach of biotherapies.

Immunotherapeutic approaches, such as immune-cell–based therapies—including CAR T cells—and immune checkpoint inhibitors, have transformed cancer treatment, particularly in hematological malignancies. However, their efficacy in solid tumors remains limited due to the immunosuppressive tumor microenvironment and the dense tumor stroma, which creates physical barriers that restrict immune-cell infiltration. I will present several strategies that harness the unique properties and remotely activatable features of metallic nanoparticles to overcome resistance mechanisms and enhance immunotherapy in solid cancers.

Extracellular vesicles (EVs) are membrane-bound nanovesicles released by all cell types and circulating in body fluids, where they play essential roles in immune regulation, tissue regeneration, and disease progression. By transporting nucleic acids, proteins, and lipids between cells, they represent highly promising cell-free biotherapeutics, particularly in the case of stem-cell–derived EVs. However, their clinical translation remains hindered by significant challenges, including scalable GMP-compliant bioproduction, batch-to-batch reproducibility, efficient isolation of potent EV subfractions, and advanced engineering for targeted delivery. This presentation will highlight breakthrough technologies developed in our laboratory for high-throughput EV bioproduction, engineering, and AI-assisted characterization. Our physics-driven approaches—including turbulence-enhanced EV production, EV encapsulation within carrier hydrogels, and multimodal analytical platforms—are now accessible to academic and industrial partners through IVETh, designated in 2022 as a national biotherapy and bioproduction integrator.