Tao Sheng

Bio: Tao Sheng is an academic researcher from Zhejiang University. The author has contributed to research in topics: Medicine & Transdermal. The author has an hindex of 1, co-authored 3 publications receiving 2 citations.

Glucose-responsive microneedle patch for closed-loop dual-hormone delivery in mice and pigs

Abstract: Insulin and glucagon secreted from the pancreas with dynamic balance play a vital role in regulating blood glucose levels. Although distinct glucose-responsive insulin delivery systems have been developed, the lack of a self-regulated glucagon release module limits their clinical applications due to the potential risk of hypoglycemia. Here, we describe a transdermal polymeric microneedle patch for glucose-responsive closed-loop insulin and glucagon delivery to achieve glycemic regulation with minimized risk of hypoglycemia. The glucose-responsive phenylboronic acid units can bind to glucose to reversibly shift the net charge (from positive to negative) of the entire polymeric matrix within microneedles. Therefore, the release ratio of the negatively charged insulin and the positively charged glucagon analog from the patch can be dynamically tuned upon the fluctuation of blood glucose levels to realize glycemic homeostasis. In both chemically induced type 1 diabetic mouse and minipig models, this glucose-responsive dual-hormone microneedle patch demonstrated tight long-term regulation in blood glucose levels (>24 hours in minipigs).

Unmanned Aerial Vehicle Mediated Drug Delivery for First Aid

Abstract: Timely administration of key medications toward patients with sudden diseases is critical to saving lives. However, slow transport of first‐aid therapeutics and the potential absence of trained people for drug usage can lead to severe injuries or even death. Herein, an unmanned aerial vehicle (UAV)‐mediated first‐aid system for targeted delivery (uFAST) is developed. It allows unattended administration of emergency therapeutics‐loaded transdermal microneedle (MN) patches toward patients to relieve symptoms by a contact‐triggered microneedle applicator (CTMA). The implementability and safety of the uFAST for first aid is demonstrated in a severe hypoglycemic pig model by automatically delivering a glucagon patch with immediate and bioresponsive dual release modes. This platform technique may facilitate the development of UAV‐mediated first‐aid treatments for other sudden diseases.

Strategies for Browning Agent Delivery.

Abstract: Obesity expands as a global climbing epidemic that is often correlated to cardiovascular diseases and endocrine disorders. Converting white adipocytes to brown adipocytes for enhanced energy expenditure has recently emerged as a promising anti-obesity treatment. However, the conventional approaches to apply browning agents systematically suffer from off-target effects, multiple dosage requirements, and poor patient compliance. To date, various delivery strategies have been reported to deliver browning agents for obesity treatment in a safer and more controllable manner. This review will discuss the latest designs in browning agent delivery systems with a focus on nanomedicines and transdermal patches.

Protein-Delivering Nanocomplexes with Fenton Reaction-Triggered Cargo Release to Boost Cancer Immunotherapy.

Abstract: Immunotherapeutic efficacy of tumors based on immune checkpoint blockade (ICB) therapy is frequently limited by an immunosuppressive tumor microenvironment and cross-reactivity with normal tissues. Herein, we develop reactive oxygen species (ROS)-responsive nanocomplexes with the function of ROS production for delivery and triggered release of anti-mouse programmed death ligand 1 antibody (αPDL1) and glucose oxidase (GOx). GOx and αPDL1 were complexed with oligomerized (-)-epigallocatechin-3-O-gallate (OEGCG), which was followed by chelation with Fe3+ and coverage of the ROS-responsive block copolymer, POEGMA-b-PTKDOPA, consisting of poly(oligo(ethylene glycol)methacrylate) (POEGMA) and the block with thioketal bond-linked dopamine moieties (PTKDOPA) as the side chains. After intravenous injection, the nanocomplexes show prolonged circulation in the bloodstream with a half-life of 8.72 h and efficient tumor accumulation. At the tumor sites, GOx inside the nanocomplexes can produce H2O2 via oxidation of glucose for Fenton reaction to generate hydroxyl radicals (•OH) which further trigger the release of the protein cargos through ROS-responsive cleavage of thioketal bonds. The released GOx improves the production efficiency of •OH to kill cancer cells for release of tumor-associated antigens via chemodynamic therapy (CDT). The enhanced immunogenic cell death (ICD) can activate the immunosuppressive tumor microenvironment and improve the immunotherapy effect of the released αPDL1, which significantly suppresses primary and metastatic tumors. Thus, the nanocomplexes with Fenton reaction-triggered protein release show great potentials to improve the immunotherapeutic efficacy of ICB via combination with CDT.

Microneedle Array Patch Made of Kangfuxin/Chitosan/Fucoidan Complex Enables Full-Thickness Wound Healing

Abstract: Skin wound caused by external injury is usually difficult to be cured by conventional topical administration because of its poor drug diffusion across the stratum corneum. It has been recognized that stratum corneum is the major obstacle for transdermal drug delivery. To address this issue, microneedles (MNs) have been developed to penetrate the stratum corneum of the skin and then form micron-sized pores between the epidermis and the dermis layers. As such, biomacromolecule drugs and/or insoluble drug molecules can be allowed for effective transdermal penetration. A multifunctional microneedle array patch that can avoid wound infection and promote tissue remolding has important value for wound healing. Among others, marine polysaccharides have attracted much attention in multifarious biomedical applications due to their excellent (bio)physical and chemical properties. Herein, we developed a microneedle array patch using a blend of kangfuxin (KFX), chitosan (CS), and fucoidan (FD), named KCFMN, for accelerating full-thickness wound healing. The traditional Chinese medicine KFX extracted from Periplaneta americana (PA) has effective bio-functions in promoting wound healing. The macro-/micro-morphology and (bio)physicochemical properties of such composite microneedles were also studied. We showed that the KCFMN patch displayed noticeable antibacterial properties and good cytocompatibility. In particular, the KCFMN patch significantly accelerated the wound healing development in a full-thickness wound in rats by improving the epithelial thickness and collagen deposition. Thus, this versatile KCFMN patch has great prospects as a dressing for full-thickness wound healing.

Artificial Intelligence-Assisted Bioinformatics, Microneedle, and Diabetic Wound Healing: A "New Deal" of an Old Drug.

Abstract: Diabetic wounds severely influence life, facing grand challenges in clinical treatments. The demand for better treatment is growing dramatically. Diabetic wound healing is challenging because of inflammation, angiogenesis disruptions, and tissue remodeling. Based on sequencing results of diabetic patients' skins and artificial intelligence (AI)-assisted bioinformatics, we excavate a potential therapeutic agent Trichostatin A (TSA) and a potential target histone deacetylase 4 (HDAC4) for diabetic wound healing. The molecular docking simulation reveals the favorable interaction between TSA and HDAC4. Taking advantage of the microneedle (MN) minimally invasive way to pierce the skin barrier for drug administration, we develop a swelling modified MN-mediated patch loaded with TSA to reduce the probability of injection-caused iatrogenic secondary damage. The MN-mediated TSA patch has been demonstrated to reduce inflammation, promote tissue regeneration, and inhibit HDAC4, which provides superior results in diabetic wound healing. We envisage that our explored specific drug TSA and the related MN-mediated drug delivery system can provide an innovative approach for diabetic wound treatment with simple, effective, and safe features and find a broad spectrum of applications in related biomedical fields.