Advancements in Nano-Delivery Systems for Photodynamic and Photothermal Therapy to Induce Immunogenic Cell Death in Tumor Immunotherapy

Abstract

Inducing immunogenic cell death (ICD) can tackle the issue of low immune response levels in tumor immunotherapy. Photodynamic therapy (PDT) uses photosensitizers to generate reactive oxygen species that kill tumor cells, while photothermal therapy (PTT) directly uses heat from photothermal converters to destroy tumor cells. However, these single treatments have their limitations. The development of optical therapy nanodelivery systems, along with the combination of PTT/PDT with chemotherapy and immunotherapy, offers new strategies for tumor immunotherapy. This article explores the application of PDT and PTT mediated by nanodelivery systems in promoting immunogenic cell death in tumor cells. This article explores nano-delivery systems that precisely release photosensitizers to boost efficacy and reduce toxicity. It also discusses their potential for combination therapy through co-delivery, utilizing multimodal strategies to enhance both phototherapy and chemotherapy, thus improving anticancer effectiveness.

Keywords: delivery system; immunogenic cell death; nano; photodynamic therapy; photothermal therapy.

Figure 1

Immunogenic cell death induced by PDT/ PTT in vivo.

Figure 2

(A) A schematic illustration of the synthetic route of Mn@CaCO₃/ICG@siRNA and the mechanism of the nanoprobe-mediated photodynamic tumor immunotherapy in vivo. Reproduced from Liu Y, Pan Y, Cao W, Xia F, Liu B, Niu J, Alfranca G, Sun X, Ma L, de la Fuente JM, Song J, Ni J, Cui D. A tumor microenvironment responsive biodegradable CaCO₃/MnO₂-based nanoplatform for the enhanced photodynamic therapy and improved PD-L1 immunotherapy. Theranostics. 2019 Sep 21;9(23):6867-6884. © The author(s).Creative Commons Attribution License. (B) The cancer immunity cycle and roles of PDT and immune checkpoint inhibitors. Reproduced from Sasaki M, Tanaka M, Kojima Y, et al. Anti-tumor immunity enhancement by photodynamic therapy with talaporfin sodium and anti-programmed death 1 antibody. Molecular Therapy-Oncolytics. 2023;28:118–131. © 2023 The Authors. CC BY license.

Figure 3

Schematic diagram of HCCO reversing drug resistance and enhancing PDT in cancer stem cells. (A) Preparation of HCCOs. (B) HCCO reverses the CSC immunosuppressive microenvironment and induces irreversible DNA damage to inhibit breast cancer recurrence and metastasis. Reproduced from Wang T, Tao J, Wang B, et al. Reversing resistance of cancer stem cells and enhancing photodynamic therapy based on hyaluronic acid nanomicelles for preventing cancer recurrence and metastasis. Adv Healthcare Mater. 2024;13(4):2302597. © 2023 Wiley-VCH GmbH.

Figure 4

Schematic of phototherapy combined with ICB in cancer treatment. Reproduced from Yujie Z, Xu L, Xinyu L, et al. Combination of phototherapy with immune checkpoint blockade: theory and practice in cancer. Front Immunol. 2022;13:955920. Copyright © 2022 Zhao, Liu, Liu, Yu, Bai, Wu, Guo, Liu and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).

Figure 5

(A) Schematic representation of GOx@FeNPs-facilitated PTT synergizing with ferroptosis through the induction of ICD to enhance colorectal cancer immunotherapy. Reproduced from Li Y, Chen J, Xia Q, et al. Photothermal Fe3O4 nanoparticles induced immunogenic ferroptosis for synergistic colorectal cancer therapy. J Nanobiotechnol. 2024;22(1):630. Copyright © 2024, The Author(s). Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. (B) The process of inducing cell immunogenicity death by PDT/PTT/chemotherapy.