Simultaneous Inhibition of Heat Shock Response and Autophagy with Bimetallic Mesoporous Nanoparticles to Enhance Mild‐Temperature Photothermal Therapy

Abstract

Mild‐temperature photothermal therapy (MPTT) is a promising tumor therapeutic modality because it can avoid the damage of normal tissues near the tumor caused by excessive heat. However, its therapeutic effect is severely impaired because tumor cells can develop heat resistance and self‐repair by activating heat shock response and cell autophagy. Herein, a tannic acid–iron ion metal organic framework‐coated, chloroquine (CQ)‐loaded mesoporous PdPt nanosystem (TF‐CQ@mPdPt) is developed to enhance MPTT by simultaneous suppression of heat shock response and autophagy. TF‐CQ@mPdPt exhibits good peroxidase (POD)‐mimic activity and photothermal performance. As a result, the reactive oxygen species generated by POD‐mediated decomposition of endogenous hydrogen peroxide damage mitochondria, leading to limitation of adenosine triphosphate supply, which suppresses the upregulation of heat shock proteins of tumor cells during MPTT, making tumor cell more sensitive to heat stress. Concurrently, CQ released from TF‐CQ@mPdPt during MPTT inhibits cell autophagy, thereby interrupting the self‐repair pathway of tumor cells. Consequently, TF‐CQ@mPdPt‐mediated MPTT significantly enhances its therapeutic effect, effectively inhibiting tumor progression in 4T1 tumor‐bearing mice. This study presents a novel strategy to enhance MPTT by simultaneously suppressing heat shock response and autophagy.

MXene‐Mediated Catalytic Redox Reactions for Biomedical Applications

“…Based on this, multiple MXenes (e. g., Nb 2 C, Ti 3 C 2 , and Mo 2 C) have been found to convert NIR light into heat, thus achieving effective tumor hyperthermia [61] . However, high temperature inevitably causes the damage to normal tissues [62] . As a feasible method, researchers have attempted to explore the application of the light‐to‐heat MXenes to other therapeutic strategies.…”

“…[61] However, high temperature inevitably causes the damage to normal tissues. [62] As a feasible method, researchers have attempted to explore the application of the light-to-heat MXenes to other therapeutic strategies. The enzymatic process is often temperature dependent, so researchers hope that a mild photothermal performance can promote the enzymecatalytic process to achieve high-efficiency enzyme-related therapy.…”

Nitric Oxide‐Based Nanomedicines for Conquering TME Fortress: Say “NO” to Insufficient Tumor Treatment

“…[ 186 ] The HSPs such as HSP70 and HSP90 are considered the key factor in thermoresistance, which can stabilize many proteins to induce effective antiapoptotic effects. [ 187 ] Due to the strong oxidization and nitration capability, NO derivative ONOO − could inhibit the expression of HSP, thus holding great potential to reduce the thermoresistance of cancer cells. Therefore, Hu et al.…”

“Three Musketeers” Enhances Photodynamic Effects by Reducing Tumor Reactive Oxygen Species Resistance

“…These ROS metabolic pathways complement each other and work together to maintain the equilibrium of intracellular ROS concentration . Although inhibition of the ROS metabolic pathway has been applied in current studies, these methods are usually limited to one aspect and thus have no significant effect. , This is because, during such therapy, tumor cells are able to balance the excess ROS in cells in different ways through other complementary signal pathways and still exhibit effective PDT resistance, which severely hinders tumor therapy.…”