GSH‐Responsive Organosilica Hybrid Nanosystem as a Cascade Promoter for Enhanced Starvation and Chemodynamic Therapy

Abstract

Glucose oxidase (GOD)-mediated starvation therapy (ST) that causes intratumoral glucose depletion is a promising strategy for tumor treatment. However, the ultimate efficacy is inevitably limited by tumor hypoxia, as oxygen is a key component in the consumption of glucose by GOD. In this study, a kind of glutathione (GSH)-responsive organosilica hybrid micelles loaded with Mn 3 O 4 and GOD (denoted as Mn 3 O 4 @PDOMs-GOD) is ingeniously designed for enhanced ST and chemodynamic therapy (CDT). Specifically, the internalized Mn 3 O 4 @PDOMs-GOD in tumor cells consumes intracellular glucose and oxygen (O 2 ) under the catalysis of GOD to generate hydrogen peroxide (H 2 O 2 ), which is subsequently decomposed by Mn 3 O 4 to liberate O 2 . This cyclically regenerated O 2 will form a virtuous cycle of O 2 and H 2 O 2 compensation to enhance the ST outcome. Meanwhile, Mn 3 O 4 can oxidize and deplete the overexpressed GSH in the tumor microenvironment (TME) to release Mn 2+ , which then catalyzes H 2 O 2 into highly toxic hydroxyl radicals (•OH) to accomplish chemodynamic therapy (CDT). Both in vitro and in vivo experiment results demonstrate the significant antitumor efficacy of Mn 3 O 4 @PDOMs-GOD by the cooperatively enhanced ST and CDT, suggesting the feasibility to develop promising therapeutic platforms with higher treatment efficacies.

Self-Powered Biosensor for a Highly Efficient and Ultrasensitive Dual-Biomarker Assay

“…Next, we explored the electrochemical activity of GOD by CV and LSV in the anode. In Figure c,d, there was an obvious redox peak of GOD after addition of 5 mM glucose, i.e., −0.47 V. Meanwhile, the reaction of O 2 consumption is C 6 H 12 O 6 + O 2 + H 2 O → GOD C 6 H 12 O 7 + H 2 O 2 , , indicating that the active center of GOD could transfer electrons to the anode and that the redox process is reversible. These results indicate the successful assembly of the cathode and anode.…”

Multifunctional nanomedicines-enabled chemodynamic-synergized multimodal tumor therapy via Fenton and Fenton-like reactions

“…Although H 2 O 2 can be converted to oxygen under the action of catalase, but the limited H 2 O 2 in the tumor microenvironment also limits the intrinsic oxygen production. Based on the above situation, a great quantity of nanomedicines with self-supplied oxygen and hydrogen peroxide have been developed 174 , 175 . Besides, Professor Xu proposed a closed-loop strategy for controlled oxygen delivery, release and utilization 176 .…”

Inorganic nanoparticle agents for enhanced chemodynamic therapy of tumours

“…58,[97][98][99][100][101] Recently, Wu et al developed GSH-responsive organosilica hybrid micelles loaded with Mn 3 O 4 nanoparticles and GOD. 102 The Mn 3 O 4 nanoparticles could deplete the overexpressed GSH in the TME by oxidizing it, and the resultant Mn 2+ reacted with the H 2 O 2 generated by GOD and produced • OH via a Fenton-like reaction. Overall, a continuous cycle of O 2 regeneration and a cascade generation of • OH were established, which combined together enabled the GSH depletion-and glucose oxidation-mediated tumour starvation CDT.…”