SnSe Nanosheets Mimic Lactate Dehydrogenase to Reverse Tumor Acid Microenvironment Metabolism for Enhancement of Tumor Therapy

Abstract

The acidic tumor microenvironment (TME) is unfriendly to the activity and function of immune cells in the TME. Here, we report inorganic nanozymes (i.e., SnSe NSs) that mimic the catalytic activity of lactate dehydrogenase to degrade lactate to pyruvate, contributing to the metabolic treatment of tumors. As found in this study, SnSe NSs successfully decreased lactate levels in cells and tumors, as well as reduced tumor acidity. This is associated with activation of the immune response of T cells, thus alleviating the immunosuppressive environment of the TME. More importantly, the nanozyme successfully inhibited tumor growth in mutilate mouse tumor models. Thus, SnSe NSs show a promising result in lactate depletion and tumor suppression, which exemplifies its potential strategy in targeting lactate for metabolic therapy.

Endoplasmic Reticulum-Targeted Aggregation-Induced Emission Luminogen for Synergetic Tumor Ablation with Glibenclamide

“…As shown in Figure S19B–D, no significant change was observed for UV–vis absorption spectra of TPA-DMPy, while the PL spectra of TPA-DMPy were significantly red-shifted due to the transformation of the pyridine group into the pyridinium group under acidic conditions (Figure S19A). Due to the difference in metabolism, cancer cells commonly survive in a mildly acid microenvironment that prevents the antitumor immunity and the function of effector cells. , Therefore, although further studies are still needed, TPA-DMPy may contribute to the quick monitoring of tumor metabolism and ablation.…”

“…Due to the difference in metabolism, cancer cells commonly survive in a mildly acid microenvironment that prevents the antitumor immunity and the function of effector cells. 67,68 Therefore, although further studies are still needed, TPA-DMPy may contribute to the quick monitoring of tumor metabolism and ablation.…”

Nanozymes with biomimetically designed properties for cancer treatment

“…133 LDH, crucial in the lactate metabolism pathway, catalyzes the conversion of lactate to pyruvate. 134 Wang and colleagues 135 harnessed this by synthesizing SnSe nanosheets (SnSe NSs) with lactate adsorbed on their surface, creating an effective adsorption structure. SnSe NSs were found to mimic LDH, efficiently consuming lactate both in lab settings and in living organisms.…”

Nanomaterial‐Based Strategies for Preventing Tumor Metastasis by Interrupting the Metastatic Biological Processes

“…investigated another method to neutralize the TME acidity by developing tin selenide (SnSe) nanosheets, which convert lactate into pyruvate for lactate depletion by mimicking the catalytic action of LDH. [ 64 ] Lactate transport across cancer cell membranes is mediated by monocarboxylate transporters (MCTs), which are coupled with factors that mediate proton cotransportation. [ 65 ] Among these, MCT1 and MCT4 are highly expressed in different types of cancer and are correlated with tumor aggravation and poor prognosis.…”