Molecular Photoswitching Unlocks Glucose Oxidase for Synergistically Reinforcing Fenton Reactions for Antitumor Chemodynamic Therapy.

We have developed a new type of nanoparticles with potent antitumor activity photoactivatable via the combination of molecular photoswitching of spiropyran (SP) and enzymatic reaction of glucose oxidase (GOx). As two key processes involved therein, Fe(III)-to-Fe(II) photoreduction in Fe(III) metal-organic frameworks (MOFs) brings about the release of free Fe2+/Fe3+ while the photoswitching of SP to merocyanine (MC) unlocks the enzymatic activity of GOx that was pre-passivated by SP. The release of free Fe3+ boosts its hydrolysis and therefore enables the acidification of microenvironment, which is further reinforced by one of the products of the GOx-mediated glucose oxidation reaction, gluconic acid (GlcA). Based on the generation of Fe2+ and acidic milieu together with another product of the oxidation reaction, hydrogen peroxide (H2O2), these two processes jointly present triple enabling factors for generating lethal hydroxyl radicals (•OH) species via Fenton reactions and therefore oxidative stress capable of inhibiting tumor. The antitumor potency of such nanoparticle is verified in tumor-bearing model mice in vivo, proclaiming its potential as a potent and safe agent based on the unique mechanism of optically manipulating enzyme activity for synergistic antitumor therapeutics with high spatial precision, enhanced efficacy and minimized side effects.

MOFs-Based Nanoagents Enable Sequential Damage to Cancer-Associated Fibroblast and Tumor Cells for Phototriggered Tumor Microenvironment Regulation.

A composite nanoagent capable of phototriggered tumor microenvironment (TME) regulation is developed based on copper (II) metal-organic frameworks (MOFs) with encapsulation of blebbistatin (Bb) and surface modification of fibroblast activation protein-αtargeted peptide (Tp). Tp enables active targeting of the nanoagents to cancer-associated fibroblast (CAF) while near-infrared light triggers Cu2+ -to-Cu+ photoreduction in MOFs, which brings about the collapse of MOFs and the release of Bb and Cu+ . Bb mediates photogeneration of hydroxyl radicals (•OH) and therefore inhibits extracellular matrix production by inducing CAF apoptosis, which facilitates the penetration of nanoagent to deep tumor tissue. The dual-channel generation of •OH based on Bb and the Cu+ species, via distinct mechanisms, synergistically reinforces oxidative stress in TME capable of inducing immunogenic cell death, which activates the antitumor immune response and therefore reverses the immunosuppressive TME. The synergistic antitumor phototherapy efficacy of such a type of nanoagent based on the abovementioned TME remodeling is unequivocally verified in a cell-derived tumor xenograft model.

Composite Mesoporous Silica Nanoparticles with Dual-color Afterglow for Cross-correlation-based Living Cell Imaging.

Room temperature phosphorescence (RTP) materials are characterized with emission after removing the excitation source. Such long-lived emission feature possesses great potential in biological fluorescence imaging because it enables a way regarding temporal dimension for separating the interference of autofluorescence and common noises typically encountered in conventional fluorescence imaging. Herein, we constructed a new type of mesoporous silica nanoparticles (MSNs)-based composite nanoparticles (NPs) with dual-color long-lived emission, namely millisecond-level green phosphorescence and sub-millisecond-level delayed red fluorescence by encapsulating a typical RTP dye and Rhodamine dye in the cavities of the MSNs with the former acting as energy donor (D) while the latter as acceptor (A). Benefiting from the close D-A proximity, energy match between the donor and the acceptor and the optimized D/A ratio in the composite NPs, efficient triplet-to-singlet Förster resonance energy transfer (TS-FRET) in the NPs occurred upon exciting the donor, which enabled dual-color long-lived emission. The preliminary results of dual-color correlation imaging of live cells based on such emission feature unequivocally verified the unique ability of such NPs for distinguishing the false positive generated by common emitters with single-color emission feature.