Sono/Photodynamic Nanomedicine‐Elicited Cancer Immunotherapy

Abstract

Immunotherapy (e.g., cancer vaccines and checkpoint blockades), harnessing the host immune system to recognize and eradicate tumors, has emerged as one of the most potent cancer therapies. The clinical applications of cancer immunotherapies, however, have been limited by their low response rates and immune‐related adverse effects. In recent years, sono/photodynamic nanomedicines (SPNs) have received increasing attention for cancer therapy since they have been reported to mediate enhanced immunotherapy by generating reactive oxygen species under site‐specific exposure to exogenous energy sources. In particular, SPNs are capable of eliciting immunogenic cancer cell death, leading to the release of tumor‐associated antigens and damage‐associated molecular patterns. This allows for the maturation of antigen‐presenting cells, thus eliminating disseminated or metastatic tumor cells by cytotoxic CD8+ T cells. Such immunostimulatory features of SPNs provide opportunities to enhance therapeutic potential by amplifying anticancer immunity when combined with conventional immunotherapeutics, including immune checkpoint inhibitors. This review elaborates on the recent strategies and efforts undertaken by researchers to enhance SPN‐elicited cancer immunotherapy. The challenging issues and opportunities for SPNs in the activation of innate or adaptive immune responses and regulation of the tumor immunosuppressive microenvironment are also described.

Photodynamic Therapy—Current Limitations and Novel Approaches

“…For this reason, SDT and PDT synergistic treatment strategy may offer a more effective treatment than monotherapy ( Abrahamse and Hamblin, 2016 ). In addition, sono/photodynamic combined therapy approaches were reported to improve the efficacy of various immunotherapeutic strategies used in tumors ( Shi et al, 2019 ; Li et al, 2020b ). PDT can trigger immunogenic cell death, which stimulates immune responses against dead cell antigens ( Green et al, 2009 ; Kroemer et al, 2013 ; Ng et al, 2018 ).…”

Reactive Oxygen Species in Anticancer Immunity: A Double-Edged Sword

“…Using other photosensitizers other than hypericin failed to induce the exposure of calreticulin on cell surface ( Garg et al, 2012 ), suggesting the necessity of choosing suitable photosensitizers or choosing suitable drug carriers to afford enhanced affinity to ER. 2) Sonodynamic therapy is similar with PDT but employs ultrasound as the energy source ( Li et al, 2021 ), and has been reported to elicit ICD. For instance, a nanocomposite loaded with chlorin e6 (as a sonosensitizer) induced ICD via receptor-interacting protein kinase 3–dependent cell necroptosis ( Um et al, 2020 ).…”

Sonosensitized Aggregation-Induced Emission Dots with Capacities of Immunogenic Cell Death Induction and Multivalent Blocking of Programmed Cell Death-Ligand 1 for Amplified Antitumor Immunotherapy

“…13 Sonodynamic therapy (SDT), derived from PDT, that utilizes ultrasound (US) to activate the sonosensitizer to produce ROS possesses deep tissue penetration, provides a more effective and safer strategy for the treatment of deep tumors, showing unique advantages and great potential in anti-tumor immunotherapy. [14][15][16] Page 2 of 32 CCS Chemistry 6 sonosensitiser-encapsulated dot aqueous solution, followed by purification by 5000 rpm ultrafiltration for 10 min and filtration using a 0.45 μm syringe driven filter.…”