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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.

Covalent organic framework (COF) nanoparticles for interference-free targeted drug delivery to glioma remains in its infancy. Herein, hollow COF nanospheres with high crystallinity and uniformed sizes were facilely prepared via heterogeneous nucleation-growth. The prepared COF had large surface area/pore volume and exhibited appropriate degradation behavior under acid environment, where therefore doxorubicin was effectively encapsulated and exhibited a pH-sensitive release. Most charmingly, T 10 peptide that has high affinity with transferrin (Tf), was conjugated to endow the hollow COF interesting properties to specifically absorb Tf in vivo as Tf corona. For the first time, multifunctional hollow COF nanospheres (the better one named DCPT-2) were successfully synthesized to achieve interference-free cascade-targeting glioma drug delivery across the blood-brain barrier. Treatment with DCPT-2 brought an improved therapeutic outcome with significantly prolonged median survival time and low side effects. This work promised not only a potential protein corona-mediated COF-based drug delivery platform with good biocompatibility for effective and precise brain tumor therapy, but also an endogenous protein corona-mediated targeting strategy for general cancer therapy. [ABSTRACT FROM AUTHOR]

Developing an all-in-one multimodal theranostic platform that can synergistically integrate sensitive photoacoustic (PA) imaging, enhanced photothermal therapy (PTT) and photodynamic therapy (PDT) as well as the nano-enzyme activated chemodynamic therapy (CDT) presents a great challenge for the current nanomedicine design. Herein, a simple hydrothermal method was used to prepare porous molybdenum disulfide (MoS 2) nanoflowers. These nanoflowers were assembled by three dimensional (3D)-stacked MoS 2 nanosheets with plentiful pores and large surfaces, which thus exhibited enhanced photothermal conversion via light trapping and peroxidase (POD)-like activity via active defects exposure. Consequently, this 3D-MoS 2 nanostructure could be well-sealed by polyethylene glycol-polyethylenimine polymer modified with nucleolar translocation signal sequence of the LIM Kinase 2 protein (LNP) via strong electrostatic interaction, which not only benefited to stably deliver anticancer drug doxorubicin (DOX) into the tumor cells for pH/NIR-responsive chemotherapy, but also provided strong photoacoustic, photothermal performances and stimulated generation of reactive oxygen species (ROS) for imaging-guided PTT/PDT/CDT combined therapy. This work promised a simple all-in-one multimodal theranostic platform to augment the potential antitumoral therapeutic outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]