Chitosan-derived drug free "artificial beacon" simulating immunogenetic cell death cascade effector to initiate immune response for cancer therapy.

Immunogenetic cell death (ICD) is widely participated in tumor immune therapy. However, the stress responses triggered by individual ICD inducers are typically not strong enough to effectively kickstart an ICD effect and successful ICD necessitates a high level of ICD stimulus, which may be linked to dose-related toxicity. In this research, we developed a drug-free "artificial beacon" ATP/CSO@ECM that mimics the ICD cascade system to kickstart an immune response with cationic chitosan (CSO) as a bridge, which participated in integrating tumor antigens and functional damage-associated molecular patterns (DAMPs) into one effector by electrostatic interaction.

Cascade Bilateral Regulation of Ferroptosis and Immune Activation Conducted by the Electron-Accepting-Inspired Glycopolymer-Based Nanoreactor.

The immunosuppressive tumor environment, characterized by elevated redox levels, significantly impairs the effectiveness of oxidation and the immune response. Here, an electron-accepting-inspired glycopolymer-based nanoreactor (chitosan-grafted nitrobenzene nanoparticles) CNP employing hypoxia-activated group nitrobenzene was constructed to realize cascade bilateral regulation of ferroptosis and immune activation by intervening antioxidant systems. The as-prepared CNP could consume nicotinamide adenine dinucleotide phosphate (NADPH) in the hypoxia-response process, allowing it to be involved in the recycling of glutathione (GSH) and thioredoxin (Trx).

An "Iron-phagy" nanoparticle inducing irreversible mitochondrial damages for antitumor therapy.

Cellular iron is inseparably related with the proper functionalities of mitochondria for its potential to readily donate and accept electrons. Though promising, the available endeavors of iron chelation antitumor therapies have tended to be adjuvant therapies. Herein, we conceptualized and fabricated an "iron-phagy" nanoparticle (Dp44mT@HTH) capable of inducing the absolute devastation of mitochondria via inhibiting the autophagy-removal of impaired ones for promoting cancer cell death.

Active Anchoring Stimuli-Responsive Nano-Craft to Relieve Pulmonary Vasoconstriction by Targeting Smooth Muscle Cell for Hypoxic Pulmonary Hypertension Treatment.

Recently, nanotechnology-based drug delivery platforms in treating pulmonary arterial hypertension (PAH) have gradually emerged. However, large mechanical stress and shear stress in blood vessels greatly affect the retention of nanopreparative materials at lesion sites, severely limiting nanotechnology-based drug delivery. Herein, a stimuli-responsive nanocraft is rationally designed by actively anchoring E-selectin overexpressed on pulmonary arterial endothelial cells (PAECs), under hypoxic conditions, allowing effective accumulation and retention of the drug at the lesion site.