Poly(2-oxazoline) Micelles for Co-Delivery of Paclitaxel and Metronidazole Benzoate for Dual Chemotherapeutic and Antibacterial Targeting in the Tumor Microenvironment

Abstract

Tumor-resident pathogenic bacteria can promote cancer progression and reduce chemotherapy efficacy, yet strategies to simultaneously target both tumor cells and intratumoral microbes remain limited. Here, we report a poly(2-oxazoline) micelle (POx) platform co-encapsulating paclitaxel (PTX) and metronidazole benzoate (MB) to achieve concurrent delivery of anticancer and antibacterial agents. The POx/PTX/MB micelles produced monodisperse populations with high drug loading efficiency and capacity and remained stable in physiological conditions. In vitro, the co-loaded formulation retained cytotoxic activity against two triple-negative breast cancer (TNBC) cell lines and bactericidal activity against Fusobacterium nucleatum. POx/PTX/MB micelles were well-tolerated at pharmacologically relevant doses in a murine model. This work provides a feasible strategy to integrate antimicrobial therapy with chemotherapy, highlighting the potential of POx micelles as a versatile platform for targeting both cancer cells and tumor-associated pathogens. These findings support further development of combination chemotherapeutic–antimicrobial strategies for tumors harboring pathogenic bacteria.