Nanomedicines Targeting Tumor Cells or Tumor-Associated Macrophages for Combinatorial Cancer Photodynamic Therapy and Immunotherapy: Strategies and Influencing Factors.

Immunotherapy is a promising cancer treatment because of its ability to sustainably enhance the natural immune response. However, the effects of multiple immunotherapies, including ICIs, are limited by resistance to these agents, immune-related adverse events, and a lack of reasonable therapeutic targets available at the right time and place. The tumor microenvironment (TME), which features tumor-associated macrophages (TAMs), plays a significant role in resistance owing to its hypoxic microenvironment and lack of blood vessels, resulting in cancer immune evasion. To enhance immunotherapy, photodynamic therapy (PDT) can increase innate and adaptive immune responses through immunogenic cell death (ICD) and improve the TME. Traditional photosensitizers (PSs) also include novel nanomedicines to precisely target tumor cells or TAMs. Here, we reviewed and summarized current strategies and possible influencing factors for nanomedicines for cancer photoimmunotherapy.

Wei Y ，Li R ，Wang Y ，Fu J ，Liu J ，Ma X ... -  《International Journal of Nanomedicine》

Enhancing cancer immunotherapy with photodynamic therapy and nanoparticle: making tumor microenvironment hotter to make immunotherapeutic work better.

Cancer immunotherapy has made tremendous advancements in treating various malignancies. The biggest hurdle to successful immunotherapy would be the immunosuppressive tumor microenvironment (TME) and low immunogenicity of cancer cells. To make immunotherapy successful, the 'cold' TME must be converted to 'hot' immunostimulatory status to activate residual host immune responses. To this end, the immunosuppressive equilibrium in TME should be broken, and immunogenic cancer cell death ought to be induced to stimulate tumor-killing immune cells appropriately. Photodynamic therapy (PDT) is an efficient way of inducing immunogenic cell death (ICD) of cancer cells and disrupting immune-restrictive tumor tissues. PDT would trigger a chain reaction that would make the TME 'hot' and have ICD-induced tumor antigens presented to immune cells. In principle, the strategic combination of PDT and immunotherapy would synergize to enhance therapeutic outcomes in many intractable tumors. Novel technologies employing nanocarriers were developed to deliver photosensitizers and immunotherapeutic to TME efficiently. New-generation nanomedicines have been developed for PDT immunotherapy in recent years, which will accelerate clinical applications.

Thiruppathi J ，Vijayan V ，Park IK ，Lee SE ，Rhee JH ... -  《Frontiers in Immunology》

Recent advances in nanomedicines for photodynamic therapy (PDT)-driven cancer immunotherapy.

Cancer immunotherapy has made tremendous clinical progress in advanced-stage malignancies. However, patients with various tumors exhibit a low response rate to immunotherapy because of a powerful immunosuppressive tumor microenvironment (TME) and insufficient immunogenicity of tumors. Photodynamic therapy (PDT) can not only directly kill tumor cells, but also elicit immunogenic cell death (ICD), providing antitumor immunity. Unfortunately, limitations from the inherent nature and complex TME significantly reduce the efficiency of PDT. Recently, smart nanomedicine-based strategies could subtly modulate the pharmacokinetics of therapeutic compounds and the TME to optimize both PDT and immunotherapy, resulting in an improved antitumor effect. Here, the emerging nanomedicines for PDT-driven cancer immunotherapy are reviewed, including hypoxia-reversed nanomedicines, nanosized metal-organic frameworks, and subcellular targeted nanoparticles (NPs). Moreover, we highlight the synergistic nanotherapeutics used to amplify immune responses combined with immunotherapy against tumors. Lastly, the challenges and future expectations in the field of PDT-driven cancer immunotherapy are discussed.

Ji B ，Wei M ，Yang B 《Theranostics》

Targeting tumor-associated macrophages to synergize tumor immunotherapy.

Xiang X ，Wang J ，Lu D ，Xu X ... -  《-》

Combining Nanomedicine and Immunotherapy.

Shi Y ，Lammers T 《-》