Biodegradable NIR‐II Pseudo Conjugate Polymeric Nanoparticles Amplify Photodynamic Immunotherapy via Alleviation of Tumor Hypoxia and Tumor‐Associated Macrophage Reprogramming

Abstract

Photodynamic therapy (PDT) has achieved great success in cancer treatment. Despite its great promise, the efficacy of photodynamic immunotherapy can be limited by the hypoxia in solid tumors which is closely related to the abnormal tumor vasculature. These abnormal vasculatures are a hallmark of most solid tumors and facilitate immune evasion. Therefore, tumor vascular normalization is developed as a promising strategy to overcome tumor hypoxia, resulting in improved cancer therapy. Here, a NIR‐II bio‐degradable pseudo‐conjugate polymer (PSP)‐based photodynamic polymer is designed to deliver a vascular normalization agent, i.e., regorafenib (Reg) in nanoparticles (NP‐PDT@Reg). NP‐PDT@Reg under 808 nm laser irradiation (NP‐PDT@Reg + L) can efficiently release Reg to improve the tumor hypoxia via vascular normalization, making more NP‐PDT@Reg and oxygen enter the tumors. Moreover, NP‐PDT@Reg + L can further result in generation of more reactive oxygen species (ROS) to eradicate tumor cells while inducing immunogenic cell death (ICD) to activate anti‐tumor immune responses. In addition, Reg can reprogram TAM from a pro‐tumor M2 phenotype to a tumor‐killing M1 phenotype as well, thereby reversing the immunosuppressive tumor microenvironment. Taken together, the current study provides an innovative perspective on the development of novel nanomaterials to overcome the limitations in photodynamic immunotherapy.

Advances in Nanoplatforms for Immunotherapy Applications Targeting the Tumor Microenvironment

“…Hypoxic TME is a typical characteristic of most solid tumors, which significantly limits nutrients and oxygen supply to the interior regions of the tumor , and increases tumor angiogenesis, aggressiveness, metastasis, and multidrug resistance. , Tumor hypoxia affects the metabolic activity of cells in the TME, making cells adapt to hypoxia stress, thus affecting the activity of pro-inflammatory immune cells and promoting tumor malignancy transformation. Tumor hypoxia can also induce immune cells (e.g., TAM) to convert to an immunosuppressive phenotype, resulting in upregulation of immunosuppressive Treg cells in tumors .…”

Anatase TiO2−x and zwitterionic porphyrin polymer-based nanocomposite for enhanced cancer photodynamic therapy

“…Then, the long-lived triplet state of TiO 2−x @TFPC ( 3 TiO 2−x @TFPC) is transformed from the photo-excited 1 TiO 2−x @TFPC. Finally, 1 O 2 is produced through the reaction between 3 TiO 2−x @TFPC and the surrounding ground state oxygen molecules 3 up the generation of 1 O 2 and improves the photodynamic therapeutic activity.…”

“…To treat this disease, great efforts have been made. [1][2][3] However, cancer resistance such as chemotherapy resistance can undermine the efficacy of cancer therapies. 4 Photodynamic therapy (PDT) as a cancer treatment with specificity and non-invasiveness has been introduced into clinical trials to improve the anti-cancer effect by overcoming multidrug resistance, [5][6][7] with reduced side effects, such as physical and mental pain.…”

Near-Infrared Titania Nanoparticle-Based Photoimmunotherapy via Tumor-Microenvironment-Responsive Gene Editing of SerpinB9 for Triple-Negative Breast Cancer

“…SerpinB9 expression is a key factor in the development of resistance in immunotherapy, including immune checkpoint blockade , and photoimmunotherapy . Nanomaterial-based photoimmunotherapies mainly include photothermal therapy (PTT)- and photodynamic therapy (PDT)-induced specific antitumor immune responses. − PTT- or PDT-induced immunogenic cell death (ICD) of cancer cells offers the potential to enhance antigen-presenting cell (APC) activation and antigen presentation, thereby enhancing antitumor immunity . By elevating the temperature of tumor tissues, PTT can selectively target and eliminate primary tumors .…”