Combining High-Z Sensitized Radiotherapy with CD73 Blockade to Boost Tumor Immunotherapy.

Radiation therapy (RT) has the capacity to induce immunogenic death in tumor cells, thereby potentially inducing in situ vaccination (ISV) to prime systemic antitumor immune responses. However, RT alone is often faced with various limitations during ISV induction, such as insufficient X-ray deposition and an immunosuppressive microenvironment. To overcome these limitations, we constructed nanoscale coordination particles AmGd-NPs by self-assembling high-Z metal gadolinium (Gd) and small molecular CD73 inhibitor AmPCP. Then, AmGd-NPs could synergize with RT to enhance immunogenic cell death, improve phagocytosis, and promote antigen presentation. Additionally, AmGd-NPs could also gradually release AmPCP to inhibit CD73's enzymatic activity and prevent the conversion of extracellular ATP to adenosine (Ado), thereby driving a proinflammatory tumor microenvironment that promotes DC maturation. As a result, AmGd-NPs sensitized RT induced potent in situ vaccination and boosted CD8+ T cell-dependent antitumor immune responses against both primary and metastatic tumors, which could also be potentiated by immune checkpoint inhibitory therapy.

Novel targets for gastric cancer: The tumor microenvironment (TME), N6-methyladenosine (m6A), pyroptosis, autophagy, ferroptosis and cuproptosis.

Gastric cancer (GC) is a fatal illness, and its mortality rate is very high all over the world. At present, it is a serious health problem for any country. It is a multifactorial disease due to the rising drug resistance and the increasing global cancer burden, the treatment of GC still faces many obstacles and problems. In recent years, research on GC is being carried out continuously, and we hope to address the new targets of GC treatment through this review. At the same time, we also hope to discover new ways to fight GC and create more gospel for clinical patients. First, we discuss the descriptive tumor microenvironment (TME), N6-methyladenosine (m6A), pyroptosis, autophagy, ferroptosis, and cuproptosis. Finally, we expounded on the new or potential targets of GC treatment.

Nano-oxygenated hydrogels for locally and permeably hypoxia relieving to heal chronic wounds.

Exposed chronic wounds are usually covered by hypoxic tissues accompanied with necrosis, persistent inflammation and anaerobic infections. Since atmospheric oxygen air can only penetrate about 0.3 mm tissues, meanwhile oxygen from the circulation is difficult to reach chronic wounds through the destroyed blood vessels, a solution to deliver oxygen locally and permeably is urgently needed. Herein we report a technique to reform traditional gel-based wound dressings by adding lyophilized oxygen encapsulated nanoparticles, which can deliver dissolved oxygen locally into wound surface. This delivery technique can potentially evaluate the therapeutic effects on hypoxic epithelial, endothelial and fibroblasts in vitro. Further experiments confirm the effects on both open wounds bearing and flap transplanted diabetic mice models. Considering its biocompatibility, effectiveness and practicality, we believe our hydrogel has significant transformation value to care and accelerate the healing of various clinical wounds, especially chronic wound.

Dissolved oxygen from microalgae-gel patch promotes chronic wound healing in diabetes.

Chronic wounds in diabetes undergo a lifetime risk of developing into diabetic foot ulcers. Oxygen is crucial to wound healing by regulating cell proliferation, migration, and neovascularization. However, current oxygen therapies, including hyperbaric oxygen (HBO) and topical gaseous oxygen (TGO), mainly employ gaseous oxygen delivery, which is much less effective in penetrating the skin. Here, we introduce an oxygen-producing patch, made of living microalgae hydrogel, which can produce dissolved oxygen. The superior performance of the patch that results from its dissolved oxygen delivery is >100-fold much more efficient than TGO penetrating the skin. Further experiments indicate that the patch could promote cell proliferation, migration, and tube formation in vitro, and improve chronic wound healing and the survival of skin grafts in diabetic mice. We believe that the microalgae-gel patch can provide continuous dissolved oxygen to improve chronic wound healing.