Harnessing Dual Phototherapy and Immune Activation for Cancer Treatment: The Development and Application of BODIPY@F127 Nanoparticles

Conventional phototherapeutic agents are typically used in either photodynamic therapy (PDT) or photothermal therapy (PTT). However, efficacy is often hindered by hypoxia and elevated levels of heat shock proteins in the tumor microenvironment (TME). To address these limitations, a formylated, near-infrared (NIR)-absorbing and heavy-atom-free Aza-BODIPY dye is presented that exhibits both type-I and type-II PDT actions with a high yield of reactive oxygen species (ROS) and manifests efficient photothermal conversion by precise adjustments to the conjugate structure and electron distribution, leading to a large amount of ROS production even under severe hypoxia. To improve biosafety and water solubility, the dye with an amphiphilic triblock copolymer (Pluronic F-127), yielding BDP-6@F127 nanoparticles (NPs) is coated. Furthermore, inspired by the fact that phototherapy triggers the release of tumor-associated antigens, a strategy that leverages potential immune activation by combining PDT/PTT with immune checkpoint blockade (ICB) therapy to amplify the systemic immune response and achieve the much-desired abscopal effect is developed. In conclusion, this study presents a promising molecular design strategy that integrates multimodal therapeutics for a precise and effective approach to cancer therapy. BDP-6@F127 nanoparticles combine the real-time imaging capacities of PAI and PTI and the excellent therapeutic effects of type-I and type-II PDT and PTT, exhibiting great antitumor properties even under hypoxia. Combining BDP-6@F127 NPs with immune checkpoint blockade therapy effectively reverses the immunosuppressive microenvironment and permits effective control of distant tumors. image