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》

Engineering nanomedicines through boosting immunogenic cell death for improved cancer immunotherapy.

Gao J ，Wang WQ ，Pei Q ，Lord MS ，Yu HJ ... -  《-》

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 immunogenic cancer cell death by photodynamic therapy: past, present and future.

The past decade has witnessed major breakthroughs in cancer immunotherapy. This development has been largely motivated by cancer cell evasion of immunological control and consequent tumor resistance to conventional therapies. Immunogenic cell death (ICD) is considered one of the most promising ways to achieve total tumor cell elimination. It activates the T-cell adaptive immune response and results in the formation of long-term immunological memory. ICD can be triggered by many anticancer treatment modalities, including photodynamic therapy (PDT). In this review, we first discuss the role of PDT based on several classes of photosensitizers, including porphyrins and non-porphyrins, and critically evaluate their potential role in ICD induction. We emphasize the emerging trend of ICD induction by PDT in combination with nanotechnology, which represents third-generation photosensitizers and involves targeted induction of ICD by PDT. However, PDT also has some limitations, including the reduced efficiency of ICD induction in the hypoxic tumor microenvironment. Therefore, we critically evaluate strategies for overcoming this limitation, which is essential for increasing PDT efficiency. In the final part, we suggest several areas for future research for personalized cancer immunotherapy, including strategies based on oxygen-boosted PDT and nanoparticles. In conclusion, the insights from the last several years increasingly support the idea that PDT is a powerful strategy for inducing ICD in experimental cancer therapy. However, most studies have focused on mouse models, but it is necessary to validate this strategy in clinical settings, which will be a challenging research area in the future.

Alzeibak R ，Mishchenko TA ，Shilyagina NY ，Balalaeva IV ，Vedunova MV ，Krysko DV ... -  《Journal for ImmunoTherapy of Cancer》

Expanded ROS Generation and Hypoxia Reversal: Excipient-free Self-assembled Nanotheranostics for Enhanced Cancer Photodynamic Immunotherapy.

The efficacy of photodynamic therapy (PDT)-related cancer therapies is significantly restricted by two irreconcilable obstacles, i.e., low reactive oxygen species (ROS) generation capability and hypoxia which constrains the immune response. Herein, this work develops a self-assembled clinical photosensitizer indocyanine green (ICG) and the HSP90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) nanoparticles (ISDN) without any excipient. This work discovers that the hydrophobic interaction forces between ICG and 17-DMAG promote the photostability of ICG and its intersystem crossing (ISC) process, thereby improving the ROS quantum yield from 0.112 to 0.46. Augmented ROS generation enhances PDT efficacy and further enhances immunogenic cell death (ICD) effects. 17-DMAG inhibits the HSP90/hypoxia-inducible factor 1α (HIF-1α) axis to dramatically reverse the immunosuppressive tumor microenvironment caused by PDT-aggravated hypoxia. In a mouse model of pancreatic cancer, ISDN markedly improve cytotoxic T lymphocyte infiltration and MHC I and MHC II activation, demonstrating the superior ICD effects in situ tumor and the powerful systematic antitumor immunity generation, eventually achieving vigorous antitumor and recurrence resistance. This study proposes an unsophisticated and versatile strategy to significantly improve PDT efficacy for enhancing systemic antitumor immunity and potentially extending it to multiple cancers.

Yang J ，Ren B ，Yin X ，Xiang L ，Hua Y ，Huang X ，Wang H ，Mao Z ，Chen W ，Deng J ... -  《-》