An Endogenous H₂S-Activated Nanoplatform for Triple Synergistic Therapy of Colorectal Cancer

Abstract

Overproduced hydrogen sulfide (H2S) is a highly potential target for precise colorectal cancer (CRC) therapy; herein, a novel 5-Fu/Cur-P@HMPB nanomedicine is developed by coencapsulation of the natural anticancer drug curcumin (Cur) and the clinical chemotherapeutic drug 5-fluorouracil (5-Fu) into hollow mesoporous Prussian blue (HMPB). HMPB with low Fenton-catalytic activity can react with endogenous H2S and convert into high Fenton-catalytic Prussian white (PW), which can generate in situ a high level of •OH to activate chemodynamic therapy (CDT) and meanwhile trigger autophagy. Importantly, the autophagy can be amplified by Cur to induce autophagic cell death; moreover, Cur also acted as a specific chemosensitizer of the chemotherapy drug 5-Fu, achieving a good synergistic antitumor effect. Such a triple synergistic therapy based on a novel nanomedicine has been verified both in vitro and in vivo to have high efficacy in CRC treatment, showing promising potential in translational medicine.

Research progress of stimuli-responsive ZnO-based nanomaterials in biomedical applications

“…In addition to the above findings, the endogenous signaling molecule hydrogen sulfide (H 2 S) is a key mediator of various physiological functions and pathological processes. 160 For instance, the excessive H 2 S produced by colorectal cancer becomes a high potential target for disease treatment, 161 favoring the construction of endogenous gas signal activation nanoplatform. As is known to all, ZnO NPs are gas-sensing materials that have attracted much attention, and new gas sensors derived from them can be used for in vitro real-time detection of dangerous gases such as H 2 S 162 and ammonia, 163 with low cost, weak toxicity, good responsiveness as well as easy structure control.…”

Modulation of Macrophages Using Nanoformulations with Curcumin to Treat Inflammatory Diseases: A Concise Review

“…Researchers have also proposed a cyclodextrin-based Cur delivery system to improve the bioavailability and antioxidant stability of Cur [ 87 ], and achieve targeted liver cancer therapy [ 88 ]. In addition, Cur, acting as a chemotherapeutic agent, can be encapsulated within HMPB NPs to achieve enhanced tumor cell apoptosis by amplifying autophagy in tumor cells [ 89 ]. Although various nanocarriers have been emerging in the design of Cur delivery, improvement of the pharmacokinetic properties of the drug, the achievement of targeted delivery to the lesion site, and the realization of microenvironment-responsive drug delivery are still key points in obtaining excellent antitumor or anti-inflammatory effects.…”

Hydrogen sulfide activatable metal-organic frameworks for Fluorescence Imaging-Guided Photodynamic Therapy of colorectal cancer

“…High content of H 2 S (0.3-3.4 mmol L −1 ) as a unique feature of CRC played vital important role in the progression of CRC (Chen et al, 2022b). To investigate whether the MOF could be to "on" in CRC cells.…”

“…In addition to the microenvironment features that numerous tumors share, a unique physiological feature in CRC is the high expression of endogenous hydrogen sulfide (H 2 S) (Shi et al, 2018;Tao et al, 2019). A growing body of evidence suggests that the overexpression of cystathionine-β-synthase (CBS) promotes the H 2 S production in CRC to support tumor cell bioenergetics, proliferation, migration, and invasion (Szabo et al, 2013;Chen et al, 2022a). Accordingly, H 2 S can serve as a specific stimulator of the nanoplatform for selectively drug release, targeted imaging and therapy for CRC (Ma et al, 2017;Chen et al, 2019;Shi et al, 2019;Su et al, 2022).…”