Recyclable Endogenous H₂S Activation of Self‐Assembled Nanoprobe with Controllable Biodegradation for Synergistically Enhanced Colon Cancer‐Specific Therapy

Abstract

Excessive production of hydrogen sulfide (H2S) plays a crucial role in the progress of colon cancer. Construction of tumor‐specific H2S‐activated smart nanoplatform with controllable biodegradation is of great significance for precise and sustainable treatment of colon cancer. Herein, an endogenous H2S triggered Co‐doped polyoxometalate (POM‐Co) cluster with self‐adjustable size, controlled biodegradation, and sustainable cyclic depletion of H2S/glutathione (GSH) is designed for synergistic enhanced tumor‐specific photothermal and chemodynamic therapy. The designed POM‐Co nanocluster holds H2S responsive “turn‐on” photothermal property in colon cancer via self‐assembling to form large‐sized POM‐CoS, enhancing the accumulation at tumor sites. Furthermore, the formed POM‐CoS can gradually biodegrade, resulting in release of Co2+ and Mo6+ for Co(II)‐catalyzed •OH production and Russell mechanism‐enabled 1O2 generation with GSH consumption, respectively. More importantly, the degraded POM‐CoS is reactivated by endogenous H2S for recyclable and sustainable consumption of H2S and GSH, resulting in tumor‐specific photothermal/chemodynamic continuous therapy. Therefore, this study provides an opportunity of designing tumor microenvironment‐driven nanoprobes with controllable biodegradation for precise and sustainable anti‐tumor therapy.

Coupling Probiotics with 2D CoCuMo‐LDH Nanosheets as a Tumor‐Microenvironment‐Responsive Platform for Precise NIR‐II Photodynamic Therapy

“…Given that both Co 2+ and Cu + ions possess Fenton reactivity to generate hydroxyl radical (·OH) for CDT, we explored the CDT performance of the CoCuMo‐LDH nanosheets incubated in different pH environments containing GSH using 3,3’,5,5’‐tetramethylbenzidine (TMB) assay. [ 55,56 ] As indicated in Figure S11 (Supporting Information), a significant increase in TMB absorption is observed when the CoCuMo‐LDH nanosheets were incubated at pH 5.4 containing GSH. In contrast, the CoCuMo‐LDH nanosheets incubated at pH 7.4 and 6.5 with GSH show inconspicuous increase in TMB absorption, illustrating the pH‐responsive ·OH generation capacity of the CoCuMo‐LDH nanosheets.…”

Design and fabrication of intracellular therapeutic cargo delivery systems based on nanomaterials: current status and future perspectives

“…For example, inorganic-based NPs are potentially toxic due to their relatively high stability, which may cause greater uncertainty in vivo . 113,114 To solve these problems, there are two main approaches, one is to increase the biodegradability of inorganic NPs, and the other is to improve their renal clearance efficiency. 115 Notably, the performance of inorganic NPs are closely related to their size, implying that their properties may change dramatically due to degradation and causing damage to tissues and organs during metabolism.…”

Recent Advances in Polyoxometalate Based Nanoplatforms Mediated Reactive Oxygen Species Cancer Therapy

“…Na 2 S was used to mimic endogenous H 2 S, and TEM images showed that Co‐POM assembled into POM‐CoS nanoclusters upon reaction with Na 2 S, and the solution also changed from colorless to black, and its hydrated particle size also changed significantly(Figure 6c). [33] Thus, in combination with the depletion of the overexpressed reduced substance H 2 S to increase ROS, Co‐POM itself assembled into POM‐CoS nanoclusters with photothermal properties. The biodegradation of POM‐CoS releases Co 2+ through the Fenton‐like reaction to produce ⋅OH and the Russell mechanism to produce 1 O 2 , enabling a synergistic photothermal and chemodynamic treatment of colon cancer.…”