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Photosensitizers (PSs) with effective reactive oxygen species generation ability against hypoxia are of great potential for clinical treatment of malignant tumors. However, complex tumor microenvironment, such as antioxidative responses and immunosuppression, would ineluctably limit the efficiency of photodynamic therapy (PDT). Herein, a molecular‐targeting photosensitizer QTANHOH is rationally designed for histone deacetylases (HDACs‐targeting photo‐immunotherapy application. The PS QTANHOH displays excellent type‐I/II PDT performance, exhibiting significant phototoxicity toward cancer cells with half maximal inhibitory concentration (IC50) less than 10 nm in both normoxia and hypoxia conditions under blue laser irradiation. Moreover, the bioactive compound could inhibit HDACs and activate the immune microenvironment to boost PDT efficacy on the immunocompetent BALB/c mice with breast cancer, leading to the eradication of solid tumor and inhibition of metastasis. Notably, the molecular‐targeting photosensitizer introduces an alternative strategy to achieve superior phototherapy for cancer therapy. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC) is endowed with a highly aggressive nature that results in distant metastases and high recurrence rates, yet limited success is realized in traditional chemotherapy. Activatable photosensitizers (PSs) may provide an effective and non‐invasive strategy to induce TNBC cell death in a precise way by offering stimuli‐responsive reactive oxygen species (ROS). However, the toxicity of ROS is often mitigated and even devitalized by the instinctive behavior of ROS resistance in TNBC cells. To address this issue, herein a small molecular self‐assembly nano‐prodrug is presented to co‐deliver an activatable PS and ROS resistance inhibitor. In TNBC cells, the overexpressed glutathione can disassemble the nano‐prodrug, thereby releasing ROS resistance inhibitor and activating the PS for photodynamic therapy and fluorescence imaging. A hybrid membrane coating‐assisted nanoparticle formation strategy is further demonstrated for efficient inhibition of tumor growth and distant metastases on both subcutaneous and orthotopic TNBC mice models. [ABSTRACT FROM AUTHOR]

The recognition and inactivation of specific pathogenic bacteria remain an enormous scientific challenge and an important therapeutic goal. Therefore, materials that can selectively target and kill specific pathogenic bacteria, without harming beneficial strains are highly desirable. Here, a material platform is reported that exploits bacteria as a template to synthesize polymers with aggregation‐induced emission (AIE) characteristic by copper‐catalyzed atom transfer radical polymerization for self‐selective killing of the bacteria that templates them with no antimicrobial resistance. The bacteria‐templated polymers show very weak fluorescence in aqueous media, however, the fluorescence is turned on upon recognition of the bacteria used as the template to synthesize the polymer even at a low concentration of 600 ng mL−1. Moreover, the incorporated AIE fluorogens (AIEgens) can act as an efficient photosensitizer for reactive oxygen species (ROS) generation after bacteria surface binding, which endows the templated polymers with the capability for selective bacterial killing. The bacterium‐templated synthesis is generally applicable to a wide range of bacteria, including clinically isolated multidrug‐resistant bacterial strains. It is envisioned that the bacterium‐templated method provides a new strategy for bacteria‐specific diagnostic and therapeutic applications. [ABSTRACT FROM AUTHOR]

The complex tumor microenvironment (TME) and nonspecific drug targeting limit the clinical efficacy of photodynamic therapy in combination with chemotherapy. Herein, a metal–organic framework (MOF) assisted strategy is reported that modulates TME by reducing tumor hypoxia and intracellular glutathione (GSH) and offers targeted delivery and controlled release of the trapped chemodrug. Platinum(IV)‐diazido complex (Pt(IV)) is loaded inside a Cu(II) carboxylate‐based MOF, MOF‐199, and an aggregation‐induced‐emission photosensitizer, TBD, is conjugated to polyethylene glycol for encapsulating Pt(IV)‐loaded MOF‐199. Once the fabricated TBD‐Pt(IV)@MOF‐199 nanoparticles are internalized by cancer cells, MOF‐199 consumes intracellular GSH and decomposes to fragments to release Pt(IV). Upon light irradiation, the released Pt(IV) generates O2 that relieves hypoxia and produces Pt(II)‐based chemodrug inside cancer cells. Concomitantly, efficient reactive oxygen species generation and bright emission are afforded by TBD, resulting in synergistic image‐guided photo‐chemo therapy with enhanced efficacies and mitigated side effects. [ABSTRACT FROM AUTHOR]

Nowadays various inorganic nanoparticles that generate highly reactive hydroxyl radical (·OH) on the basis of Fenton‐like catalytic activity of metal ions have been designed for chemodynamic therapy. However, the high level of adaptive antioxidants [glutathione (GSH)] in cancer cells could effectively consume ·OH to compromise the treatment efficiency and biosafety of these inorganic nanoparticles, and this is a general concern in chemodynamic therapy. Herein, a new biodegradable nanoscale coordination polymer (NCP) is developed by integration of cisplatin prodrug (DSCP) and iron (III) ions through a reverse microemulsion method. The DSCP in the NCPs could react with GSH to release free cisplatin, while the iron (III) ions could be reduced by GSH into iron (II) to enable Fenton reaction, subsequently leading to amplified intracellular oxidative stress. After surface modification of polyethylene glycol (PEG) and cyclo[Arg‐Gly‐Asp‐D‐Phe‐Lys(mpa)] peptide (cRGD), Fe‐DSCP‐PEG‐cRGD shows an excellent targeting effect against αvβ3‐integrin overexpressed tumor cells. Furthermore, Fe‐DSCP‐PEG‐cRGD enables significant chemo and chemodynamic therapy with dramatically enhanced therapeutic efficiency in comparison to relative monotherapies. Importantly, Fe‐DSCP‐PEG‐cRGD could be efficiently cleared out from mice through feces and urine postinjection 7 days. The NCP presented in this work is simple and economical, which shows great biodegradability and biosafety for potential clinical translation. [ABSTRACT FROM AUTHOR]

Integrated systems that offer traceable cancer therapy are highly desirable for personalized medicine. Herein, a probe is reported that is composed of a red-emissive photosensitizer (PS) with aggregation-induced emission characteristics and a built-in apoptosis sensor with activatable green emission for targeted cancer cell ablation and real-time monitoring of PS activation and therapeutic response. The probe is nonemissive in aqueous media and can be selectively uptaken by αv β3 integrin overexpressed cancer cells. Cleavage of the probe by intracellular glutathione leads to release of the apoptosis sensor and red fluorescence turn-on to report the PS activation. Upon light irradiation, the PS can generate reactive oxygen species to induce cell apoptosis and activate caspase-3/-7, which will cleave the apoptosis sensor to yield intense green fluorescence. Both the red and green emission can be obtained through a single wavelength excitation, which makes the probe very convenient for therapeutic protocol development. [ABSTRACT FROM AUTHOR]

Owing to efficient singlet oxygen (1O2) generation in aggregate state, photosensitizers (PSs) with aggregation‐induced emission (AIE) have attracted much research interests in photodynamic therapy (PDT). In addition to high 1O2 generation efficiency, strong molar absorption in long‐wavelength range and near‐infrared (NIR) emission are also highly desirable, but difficult to achieve for AIE PSs since the twisted structures in AIE moieties usually lead to absorption and emission in short‐wavelength range. In this contribution, through acceptor engineering, a new AIE PS of TBT is designed to show aggregation‐induced NIR emission centered at 810 nm, broad absorption in the range between 300 and 700 nm with a large molar absorption coefficient and a high 1O2 generation efficiency under white light irradiation. Further, donor engineering by attaching two branched flexible chains to TBT yielded TBTC8, which circumvented the strong intermolecular interactions of TBT in nanoparticles (NPs), yielding TBTC8 NPs with optimized overall performance in 1O2 generation, absorption, and emission. Subsequent PDT results in both in vitro and in vivo studies indicate that TBTC8 NPs are promising candidates in practical application. [ABSTRACT FROM AUTHOR]