Atherosclerosis is an inflammatory disease that may cause severe heart disease and stroke. Current pharmacotherapy for atherosclerosis shows limited benefits. In the progression of atherosclerosis, monocyte adhesions and inflammatory macrophages play vital roles. However, precise regulations of inflammatory immune microenvironments in pathological tissues remain challenging. Here, we report an atherosclerotic plaque-targeted selenopeptide nanomedicine for inhibiting atherosclerosis progression by reducing monocyte adhesions and inflammation of macrophages. The targeted nanomedicine has 2.2-fold enhancement in atherosclerotic lesion accumulation. The oxidation-responsibility of selenopeptide enables eliminations of reactive oxygen species and specific release of anti-inflammatory drugs, thereby reducing inflammation responses of macrophages. Notably, we find the oxidative metabolite of selenopeptide, octadecyl selenite, can bind to P-selectin in a high affinity with a dissociation constant of 1.5 μM. This in situ generated active seleno-species further inhibit monocyte adhesions for anti-inflammation in synergy. With local regulations of monocyte adhesions and inflammations, the selenopeptide nanomedicine achieves 2.6-fold improvement in atherosclerotic plaque inhibition compared with simvastatin in the atherosclerosis mouse model. Meanwhile, the selenopeptide nanomedicine also displays excellent biological safety in both mice and rhesus monkeys. This study provides a safe and effective platform for regulating inflammatory immune microenvironments for inflammatory diseases such as atherosclerosis.

Oxidative stress and inflammation are central pathophysiological processes in a traumatic spinal cord injury (SCI). Antioxidant therapies that reduce the reactive oxygen and nitrogen species (RONS) overgeneration and inflammation are proved promising for improving the outcomes. However, efficient and long-lasting antioxidant therapy to eliminate multiple RONS with effective neuroprotection remains challenging. Here, a single-atom cobalt nanozyme (Co-SAzyme) with a hollow structure was reported to reduce the RONS and inflammation in the secondary injury of SCI. Among SAzymes featuring different single metal-N sites (e.g., Mn, Fe, Co, Ni, and Cu), this Co-SAzyme showed a versatile property to eliminate hydrogen peroxide (H₂O₂), superoxide anion (O₂^•−), hydroxyl radical (·OH), nitric oxide (·NO), and peroxynitrite (ONOO⁻) that overexpressed in the early stage of SCI. The porous hollow structure also allowed the encapsulation and sustained release of minocycline for neuroprotection in synergy. In vitro results showed that the Co-SAzyme reduced the apoptosis and pro-inflammatory cytokine levels of microglial cells under oxidative stress. In addition, the Co-SAzyme combined with minocycline achieved remarkable improved functional recovery and neural repairs in the SCI-rat model.

Interest in temperature-responsive polymers has steadily grown over the past several decades, and numerous studies have been dedicated to developing temperature sensitive polymers that can be constructed into new smart materials for biomedical applications. Phase behavior of a temperature-responsive polymer plays a pivotal role in determining its biological performance in certain conditions. In addition to the additives (such as salts and proteins) in aqueous solutions, molecular weight, molecular weight distribution, and structural or compositional factors can also significantly affect the transition temperatures of the polymers. This review comprehensively describes well-established and newly developed synthetic strategies for preparing temperature-responsive polymers. The structural and compositional parameters that affect the transition temperatures and self-assembly behavior are discussed. Finally, the biomedical applications of the temperature-responsive polymers in drug delivery, immunotherapy, tissue engineering, and diagnosis are summarized.