Multifunctional Nanoplatform Combining Photothermal Therapy and Chemoimmunotherapy for the Treatment of <i>Escherichia coli</i>-Colonized Colorectal Cancer

The presence of bacteria in colorectal cancer not only induces drug inactivation but also inhibits the antitumor immune responses. Here, a multifunctional nanoplatform (IR/CP@BNP@HA) is designed to enhance antitumor photothermal therapy and chemoimmunotherapy for the treatment of bacterium-infected tumors. IR/CP@BNP@HA consists of the hyaluronic acid (HA) shell and reactive oxygen species (ROS)-responsive chitosan biguanide-functionalized biopolymer core (IR/CP@BNP), which encapsulates chemotherapy drug camptothecin (CPT) and photothermal agent IR1048. IR/CP@BNP@HA actively targeted the tumor and was subsequently degraded by abundant hyaluronidase (HAase) present in the extracellular matrix. The resultant IR/CP@BNP exhibited a size decrease and charge reversal, which facilitated a deep tumor penetration. After internalization, the exposed guanidine group of IR/CP@BNP effectively eliminated intracellular bacteria and accomplished lysosome escape. Additionally, intracellular ROS induced the precise release of drugs. More importantly, IR/CP@BNP@HA also promoted dendritic cell maturation, which in turn facilitated T-cell infiltration and maximized the antitumor immune response.