Carrier-Free Nanoassembly Suppresses Phase Separation via Ribosome-Inspired Crowding Control for Enhanced Chemo-Immunotherapy

Abstract

A carrier-free nanoassembly combines the mTOR inhibitor OSI-027 with an SN-38 prodrug to improve drug delivery and reshape the pancreatic tumor immune microenvironment. OSI-027 inhibits mTORC1/2 signaling and reduces ribosome abundance, attenuating intracellular crowding and liquid-liquid phase separation to promote macrophage repolarization toward an M1-like phenotype. In parallel, SN-38 induces tumor cell death and immunogenic responses. The formulation enhances tumor accumulation and shows antitumor activity across cell-derived xenografts, patient-derived xenografts, and genetically engineered mouse models, linking modulation of intracellular biophysics with chemo-immunotherapy.

Yiliang Lin

Assistant Professor in Chemical & Biomolecular Engineering

My research interests include soft matter engineering, wearable electronics, biointerfaces and living materials.