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Hydrogels with adhesive properties have potential for numerous biomedical applications. Here, the design of a novel, intrinsically adhesive hydrogel and its use in developing internal therapeutic bandages is reported. The design involves incorporation of “triple hydrogen bonding clusters” (THBCs) as side groups into the hydrogel matrix. The THBC through a unique “load sharing” effect and an increase in bond density results in strong adhesions of the hydrogel to a range of surfaces, including glass, plastic, wood, poly(tetrafluoroethylene) (PTFE), stainless steel, and biological tissues, even without any chemical reaction. Using the adhesive hydrogel, tissue‐adhesive bandages are developed for either targeted and sustained release of chemotherapeutic nanodrug for liver cancer treatment, or anchored delivery of pancreatic islets for a potential type 1 diabetes (T1D) cell replacement therapy. Stable adhesion of the bandage inside the body enables almost complete tumor suppression in an orthotopic liver cancer mouse model and ≈1 month diabetes correction in chemically induced diabetic mice.

Protein therapeutics offer a most effective treatment for many human diseases, including diabetes, cardiovascular diseases, and malignant tumors. Unlike most chemotherapeutics that often cause notorious side effects, many protein drugs possess a high specificity and reduced systemic toxicity. Notably, clinically used protein drugs are mostly limited to those that have extracellular effects. Protein drugs that have intracellular targets do represent a large family of protein biologics that have not been introduced into the clinic, because of the absence of translatable intracellular protein delivery vehicles. Here we report efficient and targeted cancer protein therapy in vivo by bioresponsive fluorescent photoclick hyaluronic acid (HA) nanogels. Two intracellular protein drugs, cytochrome c (CC) and granzyme B (GrB), are loaded into the nanogels with preserved bioactivity. CC- and GrB-loaded HA nanogels can effectively target and release proteins to CD44 positive MCF-7 and A549 cancer cells, yielding striking antitumor effects with a half-maximal inhibitory concentration thousands of times lower than those of clinical chemotherapeutics. Remarkably, GrB-loaded HA nanogels at a low dose of 3.8–5.7 nmol of GrB equivalents/kg exhibit complete suppression of tumor growth and minimal adverse effects in nude mice bearing subcutaneous MCF-7 human breast tumor and orthotopic A549 human lung tumor xenografts.

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a b s t r a c tThe Stepwise Behavioral Response Model (SBRM), which is a conceptual model, postulated that an organism displays a time-dependent sequence of compensatory Stepwise Behavioral Response (SBR) during exposure to pollutants above their respective thresholds of resistance. In order to prove the model, in this study, the behavioral responses (BRs) of medaka (Oryzias latipes) in the exposure of Arprocarb (A), Carbofuran (C) and Methomyl (M) were analyzed in an online monitoring system (OMS). The Self-Organizing Map (SOM) was utilized for patterning the obtained behavioral data in 0.1 TU (Toxic Unit), 1 TU, 2 TU, 5 TU, 10 TU and 20 TU treatments with control. Some differences among different Carbamate Pesticides (CPs) were observed in different concentrations and the profiles of behavior strength (BS) on SOM were variable depending upon levels of concentration. The time of the first significant decrease of BS (SD-BS) was in inverse ratio to the CP concentrations. Movement behavior showed by medaka mainly included No effect, Stimulation, Acclimation, Adjustment (Readjustment) and Toxic effect, which proved SBRM as a time-dependence model based on the time series BS data. Meanwhile, it was found that SBRM showed evident stress-dependence. Therefore, it was concluded that medaka SBR was both stress-dependent and time-dependent, which supported and developed SBRM, and data mining by SOM could be efficiently used to illustrate the behavioral processes and to monitor toxic chemicals in the environment.Crown