Designing temporal- and spatial-control multifunctional nanoformulations for synergistic photodynamic–enhanced tumour immunotherapy

The combination of light-activated therapy and immunotherapy is attracting considerable attention in tumour therapy. However, increasing the safety, quality, and durability of light-activated immune response remains a challenge. With the deepening of our immune knowledge, we are becoming aware that nanomedicine must be functioning at a suitable time and location to induce potent and durable immune responses to combat tumour growth, metastasis, or recurrence. Multifunctional inorganic nanoformulations especially photoresponsive nanoplatforms play a critical role in smart tumour immunotherapy. They can be designed to facilitate the induction of immunogenic cell death (ICD), regulate immunosuppress environments, and transport photosensitisers, immune adjuvants, and chemotherapy drugs to the right location within tumour niches. Here, we highlight the mechanism underlying photodynamic-enhanced tumour immunotherapy, exemplified the typical nanoformulations applied in tumour ablation and ROS-triggered ICD to release TAAs, reverse the immunosuppressive microenvironment, transport immune adjuvant or drugs, and relieve tumour hypoxia. Finally, the design strategies of next-generation PDT/immunotherapy nanoformulation to manipulate and control these mechanisms and to further address the limitations of the complex tumour microenvironment on the therapeutic effect and clinical transformation are discussed.