Enhanced mild-temperature photothermal therapy by pyroptosis-boosted ATP deprivation with biodegradable nanoformulation

Abstract

Background Mild-temperature photothermal therapy (mild PTT) is a safe and promising tumor therapeutic modality by alleviating the damage of healthy tissues around the tumor due to high temperature. However, its therapeutic efficiency is easily restricted by heat shock proteins (HSPs). Thus, exploitation of innovative approaches of inhibiting HSPs to enhance mild PTT efficiency is crucial for the clinical application of PTT. Results Herein, an innovative strategy is reported: pyroptosis-boosted mild PTT based on a Mn-gallate nanoformulation. The nanoformulation was constructed via the coordination of gallic acid (GA) and Mn2+. It shows an acid-activated degradation and releases the Mn2+ and GA for up-regulation of reactive oxygen species (ROS), mitochondrial dysfunction and pyroptosis, which can result in cellular ATP deprivation via both the inhibiton of ATP generation and incresed ATP efflux. The reduction of ATP and accumulation of ROS provide a powerful approach for inhibiting the expression of HSPs, which enables the nanoformulation-mediated mild PTT. Conclusions Our in-vitro and in-vivo results demonstrate that this strategy of pyroptosis-assited PTT can achieve efficient mild PTT efficiency for osteosarcoma therapy. Graphical Abstract

Self‐Destructive Copper Carriers Induce Pyroptosis and Cuproptosis for Efficient Tumor Immunotherapy Against Dormant and Recurrent Tumors

“…This is a sign that the cells were undergoing the phenomenon of pyroptosis (Figure S35, Supporting Information). [ 27 ] Our first thought was that copper ions overloading led to osmotic swelling of the cells, which then resulted in pyroptosis. To verify this speculation, we cultured 4T1 cells in medium containing CuCl 2 (Cu 2+ concentration range of 32–320 µg mL −1 ).…”

Nanomedicine‐Enabled Mild Photothermal Therapy Strategies for Enhanced Antitumor Treatment

“…The combination of decreased ATP and accumulated ROS synergistically inhibited the levels of HSPs, leading to significant mPTT effects. [ 128 ] The combination of pyroptosis and mPTT offers a promising strategy for cancer therapy, as it involves rapid cell death, the release of pro‐inflammatory factors, and the inhibition of HSPs, all of which contribute to effective tumor ablation. This approach represents a novel and potentially powerful method in the field of cancer treatment.…”

Biomaterials Elicit Pyroptosis Enhancing Cancer Immunotherapy

“…[68] Mild PTT also offers the possibility of avoiding the damage of high temperatures to paracancerous tissues mitochondrial dysfunction and inducing pyroptosis. [66] Several studies have demonstrated that epigenetics may [33][34][35][36] Copyright 2023, The Royal Society of Chemistry. Copyright 2021, Wiley-VCH GmbH.…”

“…[ 68 ] Mild PTT also offers the possibility of avoiding the damage of high temperatures to paracancerous tissues mitochondrial dysfunction and inducing pyroptosis. [ 66 ] Several studies have demonstrated that epigenetics may influence the expression of GSDME, and a complex biGC@PNA combining radiofrequency‐responsive nanoparticles with epigenetic drugs can activate pyroptosis by noninvasive radiofrequency downstream, showing promising immunotherapeutic effects (Figure 8c). [ 63 ]…”