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Molecular design plays a crucial role in regulating the photophysical properties and photodynamic therapy (PDT) performance of photosensitizers (PSs); however, realizing PDT-based synergistic therapy based on sole PSs is still rarely reported. Herein, three near-infrared red type I PSs (named TP1, TP2, and TP3) were synthesized by adjusting their electron acceptors. The results demonstrated that these PSs exhibited aggregation-enhanced reactive oxygen species (ROS) generation efficiency and cyano groups on PSs can reduce ROS generation in solution while achieving efficient PDT-based synergistic therapy in cells via glutathione depletion. [ABSTRACT FROM AUTHOR]

Bright deep red/near‐infrared red (DR/NIR) active type I photosensitizers (PSs) with generating superoxide anion and hydroxyl radical have been regarded as powerful functional materials to fight the “Achilles's heel” of hypoxia from solid tumor. But some problems have still existed, for example, lacking effective molecular designed strategy or typical building block to design precisely type I PSs. In addition, the relationship between fluorescent quantum efficiency and NIR fluorescent color is inconsistent according to energy gap rule. To overcome above mentioned problems, in this work, we propose a typical building block to design precisely type I PSs with DR/NIR fluorescence and high photoluminescent quantum yield at aggregation by combining molecular design of aggregation‐induced emission and hybrid locally and charge transfer (HLCT) theory. The synthetic small molecular PSs just produce superoxide anion without any singlet oxygen production, which is ascribed to their lower T1 energy levels to suppress energy transfer from triplet state to oxygen. Two strategies of small molecular structural designing and polymeric nanoparticles modification are utilized to improve efficiency of type I ROS. More interestingly, original small molecular PSs is in capable to produce hydroxyl radical, once forming BSA encapsulated nanoparticles, obvious hydroxyl radical is appeared. [ABSTRACT FROM AUTHOR]

Type I photosensitizers (PSs) with the ability to generate reactive oxygen species (ROS) containing superoxide anion and hydroxyl radical have promising application potential for treating hypoxia tumors, but the deep mechanism of type II ROS converts to the type I ROS in the PSs is still unclear, it is urgent to reveal influencing factors about inducing type I ROS generation. Herein, six PSs with aggregation‐induced emission properties, which were fabricated with the same electronic acceptor but different electronic donors and "π‐bridge", have been successfully prepared to explore the influencing mechanism of generating superoxide anion and hydroxyl radical from organic PSs. Experimental results discovered two factors containing molecular structure and aggregated environment could decide the ROS efficiency and types of PSs. On the level of designing molecular structure, we discovered that "π‐bridge" with a lower energy level of the lowest triplet state could be beneficial for triggering the production of superoxide anion, and electronic donor of triphenylamine was an important factor in producing hydroxyl radical than another donor of dimethylamine. On the level of designing aggregates of PS‐based polymeric nanoparticles, bovine serum albumin could improve largely the generation efficiency of superoxide anion. Due to the satisfactory ROS efficiency and better biocompatibility, synthetic PSs showed excellent photodynamic therapy outcomes in vitro/vivo. [ABSTRACT FROM AUTHOR]

Near‐infrared (NIR) fluorescence imaging–guided photodynamic therapy (PDT) technology plays an important role in treating various diseases and still attracts increasing research interests for developing novel photosensitizers (PSs) with outstanding performances. Conventional PSs such as porphyrin and rhodamine derivatives have easy self‐aggregation properties in the physiological environment due to their inherent hydrophobic nature caused by their rigid molecular structure that induces strong intermolecular stacking π–π interaction, leading to serious fluorescence quenching and cytotoxic reactive oxygen species (ROS) reduction. Meanwhile, hypoxia is an inherent barrier in the microenvironment of solid tumors, seriously restricting the therapeutic outcome of conventional PDT. Aforementioned disadvantages should be overcome urgently to enhance the therapeutic effect of PSs. Novel NIR fluorescence–guided type I PSs with aggregation‐induced emission (AIE), which features the advantages of improving fluorescent intensity and ROS generation efficiency at aggregation as well as outstanding oxygen tolerance, bring hope for resolving aforementioned problems simultaneously. At present, plenty of research works fully demonstrates the advancement of AIE‐active PDT based on type I PSs. In this review, cutting‐edge advances focusing on AIE‐active NIR type I PSs that include the aspects of the photochemical mechanism of type I ROS generation, various molecular structures of reported type I PSs with NIR fluorescence and their design strategies, and typical anticancer applications are summarized. Finally, a brief conclusion is obtained, and the underlying challenges and prospects of AIE‐active type I PSs are proposed. [ABSTRACT FROM AUTHOR]

Near-infrared (NIR) fluorescence imaging-guided photodynamic therapy (PDT) technology plays an important role in treating various diseases and still attracts increasing research interests for developing novel photosensitizers (PSs) with outstanding performances. Conventional PSs such as porphyrin and rhodamine derivatives have easy self-aggregation properties in the physiological environment due to their inherent hydrophobic nature caused by their rigid molecular structure that induces strong intermolecular stacking π-π interaction, leading to serious fluorescence quenching and cytotoxic reactive oxygen species (ROS) reduction. Meanwhile, hypoxia is an inherent barrier in the microenvironment of solid tumors, seriously restricting the therapeutic outcome of conventional PDT. Aforementioned disadvantages should be overcome urgently to enhance the therapeutic effect of PSs. Novel NIR fluorescence-guided type I PSs with aggregation-induced emission (AIE), which features the advantages of improving fluorescent intensity and ROS generation efficiency at aggregation as well as outstanding oxygen tolerance, bring hope for resolving aforementioned problems simultaneously. At present, plenty of research works fully demonstrates the advancement of AIE-active PDT based on type I PSs. In this review, cutting-edge advances focusing on AIE-active NIR type I PSs that include the aspects of the photochemical mechanism of type I ROS generation, various molecular structures of reported type I PSs with NIR fluorescence and their design strategies, and typical anticancer applications are summarized. Finally, a brief conclusion is obtained, and the underlying challenges and prospects of AIE-active type I PSs are proposed., (© 2023 John Wiley & Sons Ltd.)

De novo variants in QRICH1 (Glutamine-rich protein 1) has recently been reported in 11 individuals with intellectual disability (ID). The function of QRICH1 is largely unknown but it is likely to play a key role in the unfolded response of endoplasmic reticulum stress through transcriptional control of proteostasis. In this study, we present 27 additional individuals and delineate the clinical and molecular spectrum of the individuals (n = 38) with QRICH1 variants. The main clinical features were mild to moderate developmental delay/ID (71%), nonspecific facial dysmorphism (92%) and hypotonia (39%). Additional findings included poor weight gain (29%), short stature (29%), autism spectrum disorder (29%), seizures (24%) and scoliosis (18%). Minor structural brain abnormalities were reported in 52% of the individuals with brain imaging. Truncating or splice variants were found in 28 individuals and 10 had missense variants. Four variants were inherited from mildly affected parents. This study confirms that heterozygous QRICH1 variants cause a neurodevelopmental disorder including short stature and expands the phenotypic spectrum to include poor weight gain, scoliosis, hypotonia, minor structural brain anomalies, and seizures. Inherited variants from mildly affected parents are reported for the first time, suggesting variable expressivity., (© 2021 Wiley Periodicals LLC.)