Fluorine assembly nanocluster breaks the shackles of immunosuppression to turn the cold tumor hot

Abstract

Clinical investigations have shown that a nonimmunogenic “cold” tumor is usually accompanied by few immunopositive cells and more immunosuppressive cells in the tumor microenvironment (TME), which is still the bottleneck of immune activation. Here, a fluorine assembly nanocluster was explored to break the shackles of immunosuppression, reawaken the immune system, and turn the cold tumor “hot.” Once under laser irradiation, FS@PMPt produces sufficient reactive oxygen species (ROS) to fracture the ROS-sensitive linker, thus releasing the cisplatin conjugated PMPt to penetrate into the tumors and kill the regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Meanwhile, ROS will induce potent immunogenic cell death (ICD) and further promote the accumulation of dendritic cells (DCs) and T cells, therefore not only increasing the infiltration of immunopositive cells from the outside but also reducing the immunosuppressive cells from the inside to break through the bottleneck of immune activation. The FS@PMPt nanocluster regulates the immune process in TME from negative to positive, from shallow to deep, to turn the cold tumor into a hot tumor and provoke a robust antitumor immune response.

Role of reactive oxygen species in tumors based on the ‘seed and soil’ theory: A complex interaction (Review)

“…This was characterized by increased antigen exposure and presentation, enhanced maturation of DCs and increased infiltration of active-effector CD8 + T cells ( 107 ). Li et al ( 171 ) previously explored the potential use of a fluorine-assembled nanocluster to reverse immunosuppression and reawaken the immune system. Following the production of sufficient ROS levels by fluorine assembly @ photodynamic immunotherapy for tumor (PMPt) to break ROS-sensitive connectors under laser irradiation, cisplatin-coupled PMPt is released to penetrate the tumor and kill Treg cells and MDSCs ( 171 ).…”

“…Li et al ( 171 ) previously explored the potential use of a fluorine-assembled nanocluster to reverse immunosuppression and reawaken the immune system. Following the production of sufficient ROS levels by fluorine assembly @ photodynamic immunotherapy for tumor (PMPt) to break ROS-sensitive connectors under laser irradiation, cisplatin-coupled PMPt is released to penetrate the tumor and kill Treg cells and MDSCs ( 171 ). Additionally, ROS can strongly induce ICD by increasing infiltration by DCs and T cells to turn a cold tumor into a hot tumor and stimulate an effective anti-tumor immune response ( 171 ).…”

Single-cell RNA sequencing reveals the mechanism of sonodynamic therapy combined with a RAS inhibitor in the setting of hepatocellular carcinoma

“…In 1989, Prof. Yumita first reported sonodynamic therapy (SDT) [ 17 ], which is based on photodynamic therapy (PDT). PDT could generate immunogenic cell death (ICD), accompanied by the release of high-mobility group box 1 protein (HMGB1) and adenosine triphosphate (ATP) and the exposure of calreticulin (CRT), sending the “eat me” signal and promoting the antigen presentation and maturation of dendritic cells (DCs) [ 18 ]. Also, Photothermal therapy (PTT) is a developing field that uses the strategy of employing near-infrared (NIR) irradiation to trigger drug delivery [ 19 ].…”

Biomimetic recombinant of red blood cell membranes for improved photothermal therapy

“…Commonly, administration of most therapeutic agents by conventional formulations and dosage may lead to the limited clinical applications and therapeutic index, which are due to their rapid clearance and potential immunogenicity in vivo [ 3 , 4 ]. In contrast, inherent biochemical and biophysical properties of erythrocytes make them a significant advantage over alternative technologies in terms of half-life, stability, versatility, safety and ease of manufacture as an ideal drug delivery platform [ 5 – 7 ]. Therefore, a variety of substances (e.g.…”