Transdermal Photothermal-Pharmacotherapy to Remodel Adipose Tissue for Obesity and Metabolic Disorders.

Despite the increasing prevalence of obesity, the current medications, which act indirectly on the central nervous system to suppress appetite or on the gastrointestinal tract to inhibit fat absorption, suffer from poor effectiveness and side effects. Here, we developed a transdermal mild photothermal therapy directly acting on the root of evil (subcutaneous white adipose depot) to induce its ameliorating remodeling (browning, lipolysis, and apoptosis), based on the injectable thermoresponsive hydrogel encapsulated with copper sulfide nanodots. Further, combining pharmaceutical therapy with codelivery of mirabegron leads to a strong therapeutic synergy. This method not only ensures high effectiveness and low side effects due to localized and targeted application but also remotely creates significant improvements in systemic metabolism. Specifically, as compared to the untreated group, it totally inhibits obesity development in high-fat-diet fed mice (15% less in body weight) with decreased masses of both subcutaneous (40%) and visceral fats (54%), reduced serum levels of cholesterol (54%)/triglyceride (18%)/insulin (74%)/glucose (45%), and improved insulin sensitivity (65% less in insulin resistance index). This self-administrable method is amenable for long-term home-based treatment. Finally, multiple interconnected signaling pathways are revealed, providing mechanistic insights to develop effective strategies to combat obesity and associated metabolic disorders.

Lancing Drug Reservoirs into Subcutaneous Fat to Combat Obesity and Associated Metabolic Diseases.

Obesity is a serious epidemic health problem that can cause many other diseases including type 2 diabetes and cardiovascular diseases. Current approaches to combat obesity suffer from low effectiveness and adverse side effects. Here, a new self-administrable and minimally invasive transdermal drug delivery strategy for home-based long-term treatment of obesity and other diseases is developed. Specifically, ultrathin, core-shelled, and lance-shaped polymeric drug reservoirs (micro-lances [MLs]) are readily fabricated by a thermal pressing molding method and totally implanted into subcutaneous fat by lancing through the skin. Using a diet-induced obese mouse model, it is shown that the development of obesity and associated metabolic disorders is effectively inhibited by applying therapeutic core-shelled MLs once every 2 weeks. The outstanding therapeutic effects are attributable to highly localized and biphasic drug release, as well as combination therapy based on browning transformation of white fat and enhanced insulin sensitivity.

van der Waals Heterojunction between a Bottom-Up Grown Doped Graphene Quantum Dot and Graphene for Photoelectrochemical Water Splitting.

van der Waals heterojunctions (vdWHs) formed between 2D materials have attracted tremendous attention recently due to their extraordinary properties, which cannot be offered by their individual components or other heterojunctions. Intriguing electronic coupling, lowered energy barrier, intimate charge transfer, and efficient exciton separation occurring at the atomically sharp interface promise their applications in catalysis, which, however, are largely unexplored. Herein, we demonstrate a 0D/2D vdWH between 0D graphene quantum dots (GQDs) and 2D pristine graphene sheets, simply prepared by ultrasonication of graphite powder using GQDs as intercalation surfactant. Such an all-carbon Schottky-diode-like 0D/2D vdWH is employed for the emerging photoelectrochemical catalysis (water splitting) with high performance. The demonstrated low-cost and scalable bottom-up growth of heteroatom-doped GQDs will greatly promote their widespread applications. Moreover, the mechanisms underlying GQD growth and heterojunction-mediated catalysis are revealed both experimentally and theoretically.

One-pot fabricating Fe3O4/graphene nanocomposite with excellent biocompatibility and non-toxicity as a negative MR contrast agent.

We report a facile approach to synthesize water-dispersible nanocomposite with Fe3O4 nanoparticles (NPs) attached to graphene (G), which combines the growth of Fe3O4NPs and the reduction of graphene oxide (GO) in one single step. The unique hydrophilic surface structure of Fe3O4/G nanocomposite leads to it being colloidally stable, non-cytotoxic, well-dispersible and biocompatible in aqueous solution verified via bio-experiments. In vivo tests also prove that Fe3O4/G nanocomposite, which can be cleared from the body through the metabolic processes, is harmless to the living body. Most importantly, the Fe3O4/G nanocomposite showed T2relaxivity (123.04mM(-1)s(-1)) indicating its potential as a sensitive T2 contrast agent.