Reactive oxygen species (ROS) based nanoplatforms have been considered as attractive and feasible candidates for cancer therapy. However, the activated endogenous antioxidant defense of cancer cells in response to the...

peroxide, the decrease of superoxide dismutase (SOD) activity as well as the enhancement of reactive oxygen species (ROS) production, and finally cell apoptosis. [3] Meanwhile, as basic components in human metabolism, PAs take the advantages of high biocompatibility and low systemic toxicity. [4] Unfortunately, the direct adoption of PAs (e.g., phosphate compounds) for in vivo therapies is usually prohibited by their high therapeutic dosage, short internal circulation, and nonselective cytotoxicity. [5] Thus, it is of great significance to explore an ideal PAs donor to tackle these issues.Despite that black phosphorus quantum dots (BPQDs) have been extensively applied in cancer treatment thanks to their unique biocompatibility and photothermal effects, the exploration of their potential as ions donor is still in infancy. [6] Under the stimulation of oxidative stress, ultra-small BPQDs could be degraded spontaneously to release PAs, realizing their efficient conversion from NPs to ions. [7] However, since the endogenous oxidative stimuli often vary with cell types and physical distribution, the conversion of BPQDs into ions in the intracellular environment is generally slow and uncontrollable, finally impairing their therapeutic efficacy. Therefore, it is necessary to screen a suitable exogenous stimulus to achieve controllable degradation of BPQDs. It is well documented that photodynamic therapy (PDT), by combining photosensitizers (PSs) and light, could produce ROS on demand. [8] This inspires us to integrate PSs and BPQDs into one entity to achieve lighttriggered PDT and its concomitant synergistic IIT.Metal-organic frameworks (MOFs) are regarded as one of the promising drug delivery platforms thanks to their tailorable pore sizes, high surface areas, and multi-functional frameworks. [9] Interestingly, by coupling the Hofmeister effect with the structure directing agent of triblock copolymers, hierarchically mesoporous MOFs (HMMOFs) were recently reported, which not only inherited the merits of traditional MOFs, but also contained continuous and accessible large mesopores. [10] Although such large mesopores are generally competent for the adsorption of bulky molecules such as enzymes (soft NPs with diameter of several nanometers), the related works about the immobilization of hard NPs (e.g., quantum dots) within Although ion-interference therapy (IIT) has become an intriguing option for cancer treatment, the generation of interference ions on-demand remains a challenge. Herein, a nanoplatform based on hierarchically mesoporous metal-organic frameworks (HMMOFs) is adopted to integrate black phosphorus quantum dots (BPQDs) and meso-tetra(4-carboxyphenyl) porphine (TCPP) to realize controllable phosphate anions (PAs) production in a specific cancerous region for IIT. The uniform large mesopores of HMMOFs could guarantee the selective screening and immobilization of ultra-small and monodispersed BPQDs. The TCPP in microporous domains of HMMOFs could effectively produce 1 O 2 , which not only serves as photose...

Due to the limited penetration depth of visible light and insufficient oxygen supply in hypoxic tumor tissues, the development of near‐infrared (NIR) triggered and oxygen‐independent photodynamic therapy (PDT) to generate active radicals is necessary for cancer treatment. Herein, we developed a NIR‐triggered photothermal therapy (PTT) and oxygen‐independent PDT system based on metal‐organic frameworks (MOFs), which integrated indocyanine green (ICG) and 2,2’‐azobis[2‐(2‐imidazolin‐2‐yl)propane] dihydrochloride (AIPH) as NIR‐triggered photothermal units and temperature‐sensitive free radical initiator into ZIF‐8, respectively. AIPH was introduced into ZIF‐8 via a one‐pot strategy with high loading capacity (125 mg g−1). Through the irradiation of 808 nm laser, the ICG units could efficiently absorb NIR light to rapidly raise the local temperature to 44 °C within 3 minutes. Meanwhile, the local high temperature further induced the AIPH to continuously generate toxic alkyl radicals (R−C⋅). The combination of PTT and free radical therapy is significantly better than the single treatment mode. More importantly, the NIR‐triggered synergistic therapy could induce extensive apoptosis of cancer cells in hypoxic conditions, which sheds new light on the development of MOFs‐based photochemical therapy platform in the actual tumor microenvironment.

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