Reshaping hypoxia and silencing CD73 via biomimetic gelatin nanotherapeutics to boost immunotherapy.

The ubiquitous hypoxic microenvironment at the tumor site helps to regulate hypoxic inducible factor (HIF-1α), up-regulate downstream CD73-adenosine (CD73-ADO) pathways, and further result in effector T cell function exhaustion, which is regarded as a crucial adverse factor in the poor clinical efficacy of immune checkpoint blockade therapy (ICB). How to reshape hypoxic microenvironment and silence CD73 remains a huge challenge to improve ICB therapeutic outcomes. In this study, cancer cell membrane-camouflaged gelatin nanoparticles (CSG@B16F10) were designed to co-deliver oxygen-generating agent catalase (CAT) and CD73siRNA, thus enhancing tumor oxygenation and alleviating CD73-ADO pathway-mediated T cell immunosuppression.

MMP-responsive transformation nanomaterials with IAP antagonist to boost immune checkpoint therapy.

The clinical effect of immune checkpoint therapy is limited by the poor blocking efficiency of immune checkpoints and the insufficient infiltration of tumor-specific T cells. Here, we constructed enzyme-responsive PVA-peptide conjugates (PPCs) to achieve re-assembly with enhanced accumulation in the tumor region, enable enhanced PD-L1 occupancy and improve the blocking efficiency. The self-assembled PPC-1 nanoparticles can enter tumor environment, whereas the enzyme-cleavable peptide was digested under overgenerated matrix metalloproteinases (MMP).

Hypoxia-modulatory nanomaterials to relieve tumor hypoxic microenvironment and enhance immunotherapy: Where do we stand?

The past several years have witnessed the blooming of emerging immunotherapy, as well as their therapeutic potential in remodeling the immune system. Nevertheless, with the development of biological mechanisms in oncology, it has been demonstrated that hypoxic tumor microenvironment (TME) seriously impairs the therapeutic outcomes of immunotherapy. Hypoxia, caused by Warburg effect and insufficient oxygen delivery, has been considered as a primary construction element of TME and drawn tremendous attention in cancer therapy.

Nanosystems as curative platforms for allergic disorder management.

Allergy, IgE-mediated inflammatory disorders including allergic rhinitis, asthma, and conjunctivitis, affects billions of people worldwide. Conventional means of allergy management include allergen avoidance, pharmacotherapy, and emerging therapies. Among them, chemotherapeutant intake via oral, intravenous, and intranasal routes is always the most common mean.