Obesity enhances ovarian cancer chemotherapy efficacy through C1q-mediated tumor targeting and immune activation.

Personalized protein corona significantly influences the biodistribution and therapeutic efficacy of nanomedicines, generating unique profiles that can impact treatment outcomes. Here, we demonstrate that pegylated liposomal doxorubicin (PLD) exhibits increased tumor accumulation and enhanced antitumor immunity in obese mice bearing ovarian tumor, inducing a greater capacity to inhibit tumor growth compared to normal mice. Mechanistically, the protein corona, particularly enriched with complement component 1q (C1q) in the plasma of obese mice, significantly enhances the internalization of PLD by ovarian cancer cells and elicits strong immunogenic cell death (ICD) effects. Concurrently, C1q adsorbed on PLD promotes the engulfment of apoptotic tumor cells by dendritic cells (DCs), activating T cell-mediated antitumor immune responses and amplifying the overall antitumor efficacy of PLD in obese mice. Our findings provide new insights into the role of the personalized protein corona in modulating the therapeutic response to chemotherapy and highlight the potential of targeting C1q for enhancing the efficacy of nanomedicines in cancer treatment.