Photoactivated Formation of an Extravascular Dynamic Hydrogel as an Intelligent Blood Flow Regulator to Reprogram the Immunogenic Landscape.

Long-term tumor starvation may be a potential strategy to elevate the antitumor immune response by depriving nutrients. However, combining long-term starvation therapy with immunotherapy often yields limited efficacy due to the blockage of immune cell migration pathways. Herein, an intelligent blood flow regulator (BFR) is first established through photoactivated in situ formation of the extravascular dynamic hydrogel to compress blood vessels, which can induce long-term tumor starvation to elicit metabolic stress in tumor cells without affecting immune cell migration pathways. By leveraging methacrylate-modified nanophotosensitizers (HMMAN) and biodegradable gelatin methacrylate (GelMA), the developed extravascular hydrogel dynamically regulates blood flow via enzymatic degradation. Additionally, aPD-L1 loaded into HMMAN continuously blocks immune checkpoints. Systematic in vivo experiments demonstrate that the combination of immune checkpoint blockade (ICB) and BFR-induced metabolic stress (BIMS) significantly delays the progression of Lewis lung and breast cancers by reshaping the tumor immunogenic landscape and enhancing antitumor immune responses.

Peroxynitrite-Scavenging Organosilica Nanomedicines for Light-Controllable NO Release and Precision On-Demand Glaucoma Therapy.

Nitric oxide (NO) is a promising approach for treating ocular hypertension and glaucoma. However, its clinical application is limited by its uncontrollable release and the unwanted overproduction of peroxynitrite. Herein, a denitrifying hollow mesoporous organosilica nanoparticle (HMMN) with framework cohybridization is first constructed to encapsulate S-nitroso-N-acetyl-d,l-penicillamine (SNAP) to produce SNAP@HMMN with dual capacities of selective peroxynitrite removal and controllable NO release. Featuring a large corneal permeability, the well-designed SNAP@HMMN can achieve trans-corneal delivery to reach the target trabecular meshwork (TM)/Schlemm's canal (SC) site. Upon light irradiation, the intraocular pressure (IOP) is appropriately lowered in an adjustable and long-lasting manner while the outflow tissues are protected from nitrative damage, which is expected to realize precision on-demand glaucoma therapy with little biosafety concern, promising significant clinical translational potential.