Photoactive artificial nanocatalysts that mimic natural photoenergy systems can yield clean and renewable energy. However, their poor photoabsorption capability and disfavored photogenic electron–hole recombination hinder their production. Herein, we designed two nanocatalysts with various microstructures by combining the tailored self-assembly of the meso-tetra(p-hydroxyphenyl) porphine photosensitizer with the growth of titanium dioxide (TiO₂). The porphyrin photoabsorption antenna efficiently extended the absorption range of TiO₂ in the visible region, while anatase TiO₂ promoted the efficient electron–hole separation of porphyrin. The photo-induced electrons were transferred to the surface of the Pt co-catalyst for the generation of hydrogen via water splitting, and the hole was utilized for the decomposition of methyl orange dye. The hybrid structure showed greatly increased photocatalytic performance compared to the core@shell structure due to massive active sites and increased photo-generated electron output. This controlled assembly regulation provides a new approach for the fabrication of advanced, structure-dependent photocatalysts.

Currently used drugs for glioblastoma (GBM) treatments are ineffective, primarily due to the significant challenges posed by strong drug resistance, poor blood-brain barrier (BBB) permeability, and the lack of tumor specificity. Here, we report two cationic fluorescent anticancer agents (TriPEX-ClO4 and TriPEX-PF6) capable of BBB penetration for efficient GBM therapy via paraptosis and ferroptosis induction. These aggregation-induced emission (AIE)-active agents specifically target mitochondria, effectively triggering ATF4/JNK/Alix-regulated paraptosis and GPX4-mediated ferroptosis. Specifically, they rapidly induce substantial cytoplasmic vacuolation, accompanied by reactive oxygen species generation and intracellular Ca2+ overload, thereby disrupting metabolisms and inducing non-apoptotic cell death. In vivo imaging revealed that TriPEX-ClO4 and TriPEX-PF6 successfully traversed the BBB to target orthotopic glioma and initiated effective synergistic therapy post-intravenous injection. Our AIE drugs emerged as the pioneering paraptosis inducers against drug-resistant GBM, significantly extending survival up to 40 days compared to temozolomide (20 days) in drug-resistant GBM-bearing mice. These compelling results open up new venues for the development of fluorescent anticancer drugs and innovative treatments for brain diseases.

Background: SNAREs participate in cancers progression or stress resistance. But the current conclusions on their involvement in cancers are generally unsystematic and even contradictory on roles of one SNARE in different types of cancer. It is necessary to find universal mechanisms of participation of SNAREs in cancers possessing generalizability within appropriate range for application of targeted therapy. Methods: Our study initiated with database analysis on clinical information and bulk RNA-seq data to locate potential effective target for certain cancer type. Then experiment validations/explorations were performed on clinical human sections, cell lines and xenograft models. Lentivirus (LV) were applied for gene KD, overexpression and microRNAs sponge; Bulk RNA-seq, microRNA-seq and DIA proteomics for identification, quantification, genesets/target analysis; WB, single-IF, TSA (Tyramide signal amplification) multi-IF, IHC for proteins detection using antibodies; QPCR for artificial microRNA-sponge sequences test; Other reagents/instruments applied for corresponding purposes. Results: VAMP5 is a therapeutic target for gliomas with expression selectivity. Gliomas could be divided into 2 types according to effects after VAMP5 KD. In VAMP5-KD sensitive type, PLK1, a classical gene vital for tumor growth/survival, is universally protein-level down-regulated that mediated partly via decrease of several up-reg microRNAs like mir-1301-3p and mir-12135, causing growth inhibition. While among insensitive type that VAMP5-KD is invalid for growth inhibition, PLK1 is not altered consistently, which serves as an evaluation marker for inhibition effectiveness. NDRG4 is a prediction marker for VAMP5-KD sensitivity that sensitive gliomas express higher NDRG4 than insensitive type on RNA level. Moreover, NDRG4 overexpression converts VAMP5-KD insensitive gliomas into sensitive type and additionally cause protein-level downregulation of VCAM1 and especially TNKS which also benefit the growth inhibition and PLK1 reduction partly. Except for results above, LGALS1 correlated and colocalized with VAMP5 possessing broader consistency than other membrane proteins so indicates the immune-enhancing potential of down-reg LGALS1 via KD VAMP5. Conclusions: These discoveries elucidated the mechanism of VAMP5 KD on gliomas inhibition preliminarily. New sights for glioma therapies including selective therapeutic target, prediction marker, evaluation marker, enhancing strategy and correlated immuno-checkpoint markers were concluded with further development potentials.