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H 2 S-mediated tumor therapy has received great attention due to its unique physiological activity and synergistical enhancement, but suffers from limited H 2 S donors with promised biosafety to regulate the H 2 S delivery and subsequently the elusive pathway to augment the combined therapy. Herein, a PEGylated porous molybdenum disulfide nanoflower (MSP) with abundant defects is facilely synthesized for tumor-targeted theranostics. MSP possesses good water-dispersity and high photothermal ability, which is used for photoacoustic imaging and photothermal therapy. Interestingly, MSP is selectively degraded upon exposure to superfluous glutathione (GSH) within tumor cells, the mechanism of which is investigated, as a reduction-coordination reaction. This special degradation induces redox dyshomeostasis via GSH depletion for reactive oxygen species-accumulated chemodynamic therapy. Meanwhile, the selective biodegradation of MSP regulates a sustained H 2 S release within tumor and achieves a targeted H 2 S gas therapy via enhancing the glycolysis to acidify the tumor cells (glycolysis disorder). Synergistically, these performances are further enhanced via near-infrared photothermal heating, where excellent therapeutic outcomes with good biosafety are accomplished in vitro and in vivo. These characteristics, together with the unique biodegradation and no obvious side-effects of the nanoparticles, suggest a potential therapeutic strategy for precise tumor treatments., (© 2022 Wiley-VCH GmbH.)

Exploiting zeolitic imidazolate framework (ZIF)-based nanoparticles to synergistically enhance starvation-combined chemotherapy strategies remains an urgent demand. Herein, glucose oxidase (GOX) and doxorubicin (DOX) were facilely incorporated into ZIFs for starvation-combined chemotherapy. The as-prepared DOX/GOX-loaded ZIF (DGZ) exhibited uniform size with good dispersity, effective protection of the GOX activity, and stable delivery of the drugs into tumor. Correspondingly, it could achieve the glucose- and pH-responsive degradation and thus the controllable drug release. As a result, the acidification of glucose accompanied with reactive oxygen species (ROS) production was observed for the starvation-enhanced chemotherapy and the improved degradation. Most importantly, adjustable Zn 2+ release was achieved with the biodegradation of DGZ, which thus contributed to an augmented therapeutic outcome via the Zn 2+ -induced mitochondrial dysfunction and antioxidation dyshomeostasis. These findings, synergized with the enhancement of starvation-combined chemotherapy by inhibiting the mitochondrial energy metabolism and boosting the ROS accumulation using pristine ZIF-based nanoparticles, provide a new insight into the metal-organic framework-based nanomedicine for further cancer treatments.

Functionalizing black phosphorus nanosheet (BP) with efficient drug loading and endowing mesoporous silica nanomaterials with appropriate biodegradation for controllable tumor-targeted chemo-photothermal therapy are still urgent challenges. Herein, an ordered mesoporous silica-sandwiched black phosphorus nanosheet (BP@MS) with the vertical pore coating was prepared. The strategy could not only enhance the BP's dispersity and improve its doxorubicin (DOX)-loading efficiency, but also facilitate post-modification such as PEGylation and conjugation of targeting ligand, TKD peptide, yielding BSPT. A DOX-loaded BSPT-based system (BSPTD) showed heat-stimulative, pH-responsive, and sustained release manners. In vitro and in vivo results demonstrated that BSPTD had a delayed but finally complete degradation in physiological medium, contributing to an optimal therapeutic window and good biosafety. As a result, BSPTD can achieve an effective chemo-photothermal synergistic targeted therapy of tumor. Moreover, treating by BSPTD was found to be capable of remarkably inhibiting the lung metastasis of tumor, attributing to the photothermal degradation-facilitated secondary drug delivery. Our study provided a robust strategy to functionalize BP nanosheet and biodegrade the mesoporous silica for extended biomedical applications., (Copyright © 2020 Elsevier Ltd. All rights reserved.)