Gas therapy and embolization are important treatment methods for solid tumors. In order to improve the efficacy of NO therapy and simplify the operation of interventional embolization, we designed and prepared the microacidic-gelled poly[(L-Glutamic acid- ran -L-Tyrosine)- b -L-Threonine- b -L-S-nitrosocysteine]s (PGTTSNCs, obtained by the reaction of tert-butyl nitrite with thiol side groups of poly[(L-Glutamic acid- ran -L-Tyrosine)- b -L-Threonine- b -L-Cysteines]s, PGTTCs.) for noninterventional embolization combined with NO gas therapy for solid tumors. The results of in vivo experiments indicated that PGTTSNCs from PGTTCs-6.4 (the gelled-pH value is 6.4) has significant target-accumulation and therapy effects, and at 10 days post-injection only scars were found at the tumor site. After 20 days, the tumors of model mice were completely disappeared. The method is extremely simple and efficient for solid tumors, which is not only a great innovation of tumors theranostic, but also a qualitative development in nanomaterials .
Neuropeptides are endogenous neuromodulators that have been shown to play pivotal roles in cancer initiation and progression. The phosphorylation/dephosphorylation processes are critically involved in regulating the bioactivity of peptides. This study designed chiral phosphorylated neuropeptides with distinct modification sites to examine the stereochemical regulatory mechanisms of alkaline phosphatase-mediated dephosphorylation and its biological effects on glioblastoma (GBM). The differential dephosphorylation catalyzed by alkaline phosphatase (ALP) demonstrates that both the spatial positions and quantity of modification sites significantly influence aggregation kinetics and intermolecular interactions. The dephosphorylated products derived from d-enantiomer probes inhibit GBM proliferation and invasion by disrupting cytoskeletal reorganization, while simultaneously enhancing tumor-targeted accumulation capacity and prolonging in vivo metabolic stability. These findings provide crucial insights into the stereochemical effects of chirality and terminal phosphorylation sites on peptide functionality, as well as contribute to the development for Y1R-targeted therapies for GBM and other solid tumors.