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》

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》

Combining Nanomedicine and Immunotherapy.

Shi Y ，Lammers T 《-》

Nanomaterials-Based Photodynamic Therapy with Combined Treatment Improves Antitumor Efficacy Through Boosting Immunogenic Cell Death.

Benefiting from the rapid development of nanotechnology, photodynamic therapy (PDT) is arising as a novel non-invasive clinical treatment for specific cancers, which exerts direct efficacy in destroying primary tumors by generating excessive cytotoxic reactive oxygen species (ROS). Notably, PDT-induced cell death is related to T cell-mediated antitumor immune responses through induction of immunogenic cell death (ICD). However, ICD elicited via PDT is not strong enough and is limited by immunosuppressive tumor microenvironment (ITM). Therefore, it is necessary to improve PDT efficacy through enhancing ICD with the combination of synergistic tumor therapies. Herein, the recent progress of nanomaterials-based PDT combined with chemotherapy, photothermal therapy, radiotherapy, and immunotherapy, employing ICD-boosted treatments is reviewed. An outlook about the future application in clinics of nanomaterials-based PDT strategies is also mentioned.

Jin F ，Liu D ，Xu X ，Ji J ，Du Y ... -  《International Journal of Nanomedicine》

Light-triggered photodynamic nanomedicines for overcoming localized therapeutic efficacy in cancer treatment.

Photodynamic nanomedicines have significantly enhanced the therapeutic efficacy of photosensitizers (PSs) by overcoming critical limitations of PSs such as poor water solubility and low tumor accumulation. Furthermore, functional photodynamic nanomedicines have enabled overcoming oxygen depletion during photodynamic therapy (PDT) and tissue light penetration limitation by supplying oxygen or upconverting light in targeted tumor tissues, resulting in providing the potential to overcome biological therapeutic barriers of PDT. Nevertheless, their localized therapeutic effects still remain a huddle for the effective treatment of metastatic- or recurrent tumors. Recently, newly designed photodynamic nanomedicines and their combination chemo- or immune checkpoint inhibitor therapy enable the systemic treatment of various metastatic tumors by eliciting antitumor immune responses via immunogenic cell death (ICD). This review introduces recent advances in photodynamic nanomedicines and their applications, focusing on overcoming current limitations. Finally, the challenges and future perspectives of the clinical translation of photodynamic nanomedicines in cancer PDT are discussed.

Choi J ，Sun IC ，Sook Hwang H ，Yeol Yoon H ，Kim K ... -  《-》