Sm/Co‐Doped Silica‐Based Nanozymes Reprogram Tumor Microenvironment for ATP‐Inhibited Tumor Therapy

Abstract

Current applications of multifunctional nanozymes for reprogramming the redox homeostasis of the tumor microenvironment (TME) have been severely confronted with low catalytic activity and the ambiguity of active sites of nanozymes, as well as the stress resistance from the rigorous physical environment of tumor cells. Herein, the Sm/Co‐doped mesoporous silica with 3PO‐loaded nanozymes (denoted as mSC‐3PO) are rationally constructed for simultaneously inhibiting energy production by adenosine triphosphate (ATP) inhibitor 3PO and reprogramming TME by multiactivities of nanozymes with photothermal effect assist, i.e., enhanced peroxidase‐like, catalase‐like activity, and glutathione peroxidase‐like activities, facilitating reactive oxygen species (ROS) generation, promoting oxygen content, and restraining the over‐expressed glutathione. Through the optimal regulation of nanometric size and doping ratio, the fabricated superparamagnetic mSC‐3PO enables the excellent exposure of active sites and avoids agglomeration owing to the large specific surface and mesoporous structure, thus providing adequate Sm/Co‐doped active sites and enough spatial distribution. The constructed Sm/Co centers both participate in the simulated biological enzyme reactions and carry out the double‐center catalytic process (Sm3+and Co3+/Co2+). Significantly, as the inhibitor of glycolysis, 3PO can reduce the ATP flow by cutting down the energy transform, thereby inhibiting tumor angiogenesis and assisting ROS to promote the early withering of tumor cells. In addition, the considerable near‐infrared (NIR) light absorption of mSC‐3PO can adapt to NIR excitable photothermal treatment therapy and photoexcitation‐promoted enzymatic reactions. Taken together, this work presents a typical therapeutic paradigm of multifunctional nanozymes that simultaneously reprograms TME and promotes tumor cell apoptosis with photothermal assistance.

AuPt-Loaded Cu-Doped Polydopamine Nanocomposites with Multienzyme-Mimic Activities for Dual-Modal Imaging-Guided and Cuproptosis-Enhanced Photothermal/Nanocatalytic Therapy

“…Although a higher level of H 2 O 2 and mildly acidic TME are favorable for AuPt@Cu-PDA to exert multienzymatic activities, overexpressed GSH would maintain the redox balance by scavenging ROS. Herein, the GSH depletion ability of AuPt@Cu-PDA was evaluated using 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB) . DTNB could react with GSH to produce yellow TNB, with the absorption peak at 412 nm (Figure S15).…”

“…Herein, the GSH depletion ability of AuPt@Cu-PDA was evaluated using 5,5′-dithiobis(2nitrobenzoic acid) (DTNB). 25 DTNB could react with GSH to produce yellow TNB, with the absorption peak at 412 nm (Figure S15). 26 As depicted in Figure 3g, the remaining GSH gradually decreased with the increase of incubation time and was completely consumed at 1.5 h, indicating the excellent GSH depletion capability of AuPt@Cu-PDA.…”

Preclinical Assessment of Enhanced Chemodynamic Therapy by an FeMnOx-Based Nanocarrier: Tumor-Microenvironment-Mediated Fenton Reaction and ROS-Induced Chemotherapeutic for Boosted Antitumor Activity

“…These ROS actively damage proteins, DNA, and lipids, leading to cell death. By leveraging this intrinsic process, CDT achieves a high level of specificity for tumor cells while reducing the impact on healthy tissues, thereby enhancing its therapeutic potential. − The TME characterized as a mildly acidic environment with the presence of an elevated concentration of H 2 O 2 is the optimal region for processing the pro-death oxidative Fenton reaction. In contrast to TME, normal healthy tissue lacking an acidic microenvironment plus the limited presence of H 2 O 2 is not favorable in the action of Fenton reaction, suggesting that it possesses selectively therapeutic effectiveness in inducing tumor cell death but not in healthy tissues. , The TME exhibits abnormal physiological settings, including vascular abnormalities (angiogenesis), severe hypoxia, low pH levels, overexpressed GSH, and high H 2 O 2 .…”

Transition-Metal-Based Nanozymes: Synthesis, Mechanisms of Therapeutic Action, and Applications in Cancer Treatment

“…For example, a nanozyme with glutathione peroxidase (GPx) or glutathione oxidase (GSHOx or GSH- OXD) activity can catalyze the conversion of GSH into glutathione disulfide (GSSG), which is widely used to consume GSH in the TME to destroy the redox balance for cancer treatment. 130,131 3.2. Regulation of Enzyme-like Activity.…”

“…In addition, some nanozymes that mimic the activity of other enzymes have been developed for disease diagnosis and treatment. For example, a nanozyme with glutathione peroxidase (GPx) or glutathione oxidase (GSHOx or GSH-OXD) activity can catalyze the conversion of GSH into glutathione disulfide (GSSG), which is widely used to consume GSH in the TME to destroy the redox balance for cancer treatment. , …”