A Compartmental Silica Nanoreactor for Multienzyme‐Regulated Superactive Catalytic Therapy

Abstract

Many tumor therapies take advantage of upsetting the redox balance in tumor cells, but to do so requires excessive biochemical or physical attacks. The high‐throughput simulation using multi‐pathway techniques described herein can yield an increased efficacy in bio‐oxidation. In this study, compartmental hierarchical nanoreactors are developed as an efficient multi‐pathway singlet oxygen (1O2) generation system for superactive biocatalytic tumor therapy. The penetrated super cavity and connected dual‐mesopore channels of the compartmental multienzyme nanoreactors are designed using the proposed heterogeneous template assembly for multi‐enzyme complex (superoxide dismutase (SOD)‐lactoperoxidase (LPO)) and photosensitizer molecule (indocyanine green (ICG)) encapsulation. Benefiting by the enhanced direct substrate diffusion between the interacting SOD–LPO complex and decrease in external diffusion, the parallel catalysis combined by the superactive cascade biocatalysis and enzyme‐promoted photosensitization effect is verified by this compartmental silica nanoreactor system. The parallel pathways not only make full use of the products of SOD (H2O2 and O2), but also exhibit outstanding capability for 1O2 production, at ≈2.15 and 1.70 times augmented 1O2, respectively. Both in vitro and in vivo studies demonstrate the synergetic 1O2‐mediated inhibition of tumor proliferation, lending this strategy great potential for the treatment of hypoxic tumors.

Imine-Linked Covalent Organic Framework Modulates Oxidative Stress in Alzheimer’s Disease

“…Reactive oxygen species (ROS) are a class of one-electron reduction products of oxygen such as superoxide radicals (O 2 · – ), hydrogen peroxide (H 2 O 2 ), and hydroxyl radicals (·OH). , Superoxide dismutase (SOD) and catalase (CAT) are two antioxidant enzymes capable of, respectively, converting ROS to water and oxygen. − Due to their high catalytic activity, specificity, and little side effects, SOD and CAT are being utilized as treatments to many diseases, such as inflammatory bowel disease, spinal cord injury, tumors, neuropathic pain, etc. For in vivo applications, carriers are always needed to protect and transport SOD and CAT to specific locations , because of their instability and nonspecific distribution.…”

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

“…[3][4][5][6] Nanozymes, serving as an intermedium, exert their enzyme-like activities to trigger the endogenous substances in the intracellular microenvironment for the generation of highly toxic reactive oxygen species (ROS) to kill tumor cells. [7][8][9][10][11][12] Currently, nanozymes with natural enzyme-like peroxidase (POD), [13] catalase (CAT), [14,15] glutathione peroxidase (GPx), [16,17] superoxide dismutase, [18,19] and oxidase [20] activities have been explored a lot. [3,21] However, the clinical applications of nanozymes are still confronted with bottleneck issues, such as low catalytic activity, poor selectivity, and ambiguity of active sites.…”

A Compartmentalized Nanoreactor Formed by Interfacial Hydrogelation for Cascade Enzyme Catalytic Therapy

“…Self-assembling microstructures, such as liposomes, [3] polymersomes, [4] lipid-stabilized aqueous droplets, [5] and protein-assembled virus-like structures [6] have been suggested as confined and organized microenvironments for mimicking cell structures. These microenvironments include nested vesicles, multicompartment vesicles, large-scale vesicle networks, droplet interface bilayers, double-emulsion multiphase systems and the porous inorganic materials, such as silicon dioxide (SiO 2 ) nanoparticles, [7] titanium dioxide (TiO 2 ), [8] carbon nanotubes (CNTs), [9] and metal-organic framework (MOF) nanoparticles. [10] The spatial organization of catalysts in adjacent microenvironments and porous matrices can provide substrate action channels [3c, 11, 12] that facilitate biocatalytic cascades.…”

“…[16] Recently, an isolated silica nanoreactor encapsulated multi-enzyme complexes and photosensitizer molecules with multi-pathway 1 O 2 production for efficient therapy was reported by our group. [7] Additionally, heterogeneous multi-compartmental hydrogel particles as synthetic cells were reported for an incompatible glucose@horseradish peroxidase (GO X @HRP)-catalyzed tandem reaction as a glucose-powered therapeutic strategy to kill cancer cells. [1a] However, there seems to be a contradiction between achieving the physically compartmentalized spaces and ensuring an effective linkage and transfer between the spaces at the same time.…”

“…These have been broadly applied as confined nano‐ and microreactors for separation matrices, [13] sensing, [14] drug delivery [15] and selective catalytic transformations [16] . Recently, an isolated silica nanoreactor encapsulated multi‐enzyme complexes and photosensitizer molecules with multi‐pathway 1 O 2 production for efficient therapy was reported by our group [7] . Additionally, heterogeneous multi‐compartmental hydrogel particles as synthetic cells were reported for an incompatible glucose@horseradish peroxidase (GO X @HRP)‐catalyzed tandem reaction as a glucose‐powered therapeutic strategy to kill cancer cells [1a] .…”