Cell-Membrane-Coated Cationic Nanoparticles Disguised as Macrophages for the Prevention and Treatment of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by low-grade inflammation and insulin resistance. In this process, innate immune cells play a crucial role in recognizing the stimuli (free fatty acid, lipopolysaccharide, and cytokines) and mediating the inflammatory response, contributing to the development of T2DM. Neutralizing inflammatory cytokines and blocking the inflammation cascade provide great potential for the treatment of T2DM. Here, we applied a macrophage membrane as a bait, which could specifically recognize and bind the stimuli, to encapsulate nanoparticles and capture the stimuli, further preventing inflammation. The in vivo experiment results suggest that the nanoparticles could reduce the production of proinflammatory cytokines, decrease insulin resistance, and realize significant therapeutic effects for T2DM. A potential strategy is thus offered for blocking immune response, holding a wide application in metabolic and autoimmune diseases.

A Facile Low-Dose Photosensitizer-Incorporated Dissolving Microneedles-Based Composite System for Eliciting Antitumor Immunity and the Abscopal Effect.

Nanomedicine-based photodynamic therapy (PDT) for melanoma treatment has attracted great attention. However, the complex design of polymer nanoparticles and high doses of photosensitizers used in intravenous injections (for sufficient accumulation of drugs in tumor lesions) pose a huge challenge to the commercialization and further clinical application. Herein, we fabricated the carrier-free nanoassemblies of a chlorin e6 (L-Ce6 NAs)-integrated fast-dissolving microneedles patch (L-Ce6 MNs) enriching only about 3 µg of Ce6 in the needle tips via a facile fabrication method. The L-Ce6 MNs had sufficient mechanical strength to penetrate the skin and facilitated the transportation of L-Ce6 NAs to a depth of 200-500 µm under the skin, thereby achieving efficient and accurate drug delivery to tumor lesions. In a xenograft mouse melanoma model, the L-Ce6 MNs-based PDT with low dose of Ce6 (0.12 mg/kg) exerted efficient ablation of the primary lesions in situ through reactive oxygen species (ROS) generation. More importantly, a significant abscopal effect was also elicited by activating immunogenic cell death (ICD) and releasing danger-associated molecular patterns (DAMPs), which in turn promoted dendritic cells (DCs) maturation and the subsequent antigen presentation, thereby facilitating the T-cell-mediated immune response without synergetic immunotherapies. Collectively, our findings indicate the facile, controllable, and fast-dissolving microneedles patch with a low dose of photosensitizers presented great therapeutic potential for enhanced photoimmunotherapy.

Polymer nanoparticles regulate macrophage repolarization for antitumor treatment.

We demonstrate an intrinsic antitumor effect of polymer nanoparticles (P-NPs), which could re-program tumor-associated macrophages to pro-inflammatory phenotype. The intrinsic effect of P-NPs on macrophage repolarization and its combination with other therapies provide new ideas for drug delivery, macrophage regulation and immunotherapy in cancer treatment.

Current advances in stem cell-based therapies for hair regeneration.

Alopecia is resulted from various factors that can decrease the regeneration capability of hair follicles and affect hair cycles. This process can be devastating physically and psychologically. Nevertheless, the available treatment strategies are limited, and the therapeutic outcomes are not satisfactory. According to the possible pathogenesis of nonscarring alopecia, especially androgenetic alopecia, recovering or replenishing the signals responsible for hair follicle stem cells activation is a promising strategy for hair regeneration. Recently, stem cell-based therapies, especially those based on the stem cell-derived conditioned medium (CM), which is secreted by stem cells and is rich in paracrine factors, have been widely explored as the hair regenerative medicine. Several studies have focused on altering the composition and up-regulating the amount of secretome of the stem cells, thereby enhancing its therapeutic effects. Besides, stem cell-derived exosomes, which are present in the CM as message entities, are also promising for hair regrowth. In this review, the up-to-date progress of research efforts focused on stem cell-based therapies for hair regeneration will be discussed, including their therapeutic potentials with respective merits and demerits, as well as the possible mechanisms.

Engineered nanoparticles disguised as macrophages for trapping lipopolysaccharide and preventing endotoxemia.

Endotoxemia is a severe pathophysiology induced by bacterial endotoxin (also known as lipopolysaccharide, LPS), causing high mortality in clinic due to the life-threatening syndromes, such as sepsis, shock, and multiple organ dysfunction. Removing or neutralizing endotoxin from the circulatory system has been proven to be a potential strategy for the treatment of endotoxemia. However, the selectivity and removal efficiency of existing detoxification approaches are not satisfied. Considering the crucial role of immune cells in LPS recognition and inflammation mediation, we design a disguised nanoparticle using macrophage membranes as bait to specifically capture and deactivate LPS. The in vivo experiment results demonstrate that the nanoparticles markedly weaken the immune response, reduce the inflammatory reaction, and improve the survival rate of endotoxic mice. These deceptive nanoparticles should be broadly applicable for treating a variety of diseases related to LPS, such as metabolic and vascular abnormalities in obesity, and diabetes-related diseases.