A NIR‐Light‐Activated and Lysosomal‐Targeted Pt(II) Metallacycle for Highly Potent Evoking of Immunogenic Cell Death that Potentiates Cancer Immunotherapy of Deep‐Seated Tumors

Abstract

Though platinum (Pt)‐based complexes have been recently exploited as immunogenic cell death (ICD) inducers for activating immunotherapy, the effective activation of sufficient immune responses with minimal side effects in deep‐seated tumors remains a formidable challenge. Herein, we propose the first example of a near‐infrared (NIR) light‐activated and lysosomal targeted Pt(II) metallacycle (1) as a supramolecular ICD inducer. 1 synergistically potentiates immunomodulatory response in deep‐seated tumors via multiple‐regulated approaches, involving NIR light excitation, boosted reactive oxygen species (ROS) generation, good selectivity between normal and tumor cells, and enhanced tumor penetration/retention capabilities. Specifically, 1 has excellent depth‐activated ROS production (~ 7 mm), accompanied by strong anti‐diffusion and anti‐ROS quenching ability. In vitro experiments demonstrate that 1 exhibits significant cellular uptake and ROS generation in tumor cells as well as respective multicellular tumor spheroids. Based on these advantages, 1 induces a more efficient ICD in an ultralow dose (i.e., 5 µM) compared with the clinical ICD inducer‐oxaliplatin (300 μM). In vivo, vaccination experiments further demonstrate that 1 serves as a potent ICD inducer through eliciting CD8+/CD4+ T cell response and Foxp3+ T cell depletion with negligible adverse effects. This study pioneers a promising avenue for safe and effective metal‐based ICD agents in immunotherapy.

MOF-Derived Oxygen-Deficient Titania-Mediated Photodynamic/Photothermal-Enhanced Immunotherapy for Tumor Treatment

“…Recently, immunogenic cell death (ICD) has attracted increasing attention for its ability to initiate local immune reactions and enhance immunotherapy effectiveness. , ICD inducers not only can eradicate tumor cells in situ but also initiate a cascade of events to eliminate distant tumor cells, including the release of the immunogenic damage-related molecular patterns (DAMPs) that promote phagocytosis of apoptotic cells by antigen-presenting cells and recruitment of antitumor T cells. ,, Several therapeutic approaches like chemotherapy, radiotherapy, and phototherapy have been reported to induce ICD . Phototherapy, notably nanomaterial-mediated photodynamic therapy (PDT) and photothermal therapy (PTT), is gaining prominence as a minimally invasive and highly efficient cancer treatment .…”

A novel surface-enhanced Raman based molecular identification platform for multiplexed and highly accurate clinical diagnosis of viral diseases

“…However, LFA-based methods face challenges in achieving parallel detection of multiple viruses and exhibit low analytical sensitivity, leading to a high proportion of false-negative cases. [10][11][12][13] Therefore, there is an urgent need to develop a highly sensitive molecular identification platform for multi-virus antigen detection, advancing accurate diagnostics for respiratory diseases.…”