An AIE Controlled "Off-On" Cu2+-Sensitive Probe for Early Detection of Renal Fibrosis.

Early detection of renal fibrosis (RF) is very important given that it is irreversible when it progresses to the terminal stage. A key marker of RF pathogenesis is activation of myomyofibroblasts, and its targeted imaging may be a promising approach for early detection of RF, but no study has directly imaged activation of renal myomyofibroblasts. Cu2+ plays a major role in the fibrotic activity of myofibroblasts. Herein, inspired by that Cu2+ can complex with bovine serum albumin (BSA), BSA-Ag2S quantum dots (QDs) with aggregation-induced emission (AIE) property are synthesized. Then BSA-Ag2S QDs are modified by chitosan (CS) with renal targeting and hyaluronic acid (HA) with myofibroblast targeting to obtain the AIE assay system (QDs@CS@HA). The system is simple to synthesize, and produces a rapid NIR fluorescence signal turn-on response and a low detection limit of 75 × 10-9 m to Cu2+. In addition, cellular and animal experiments have shown that QDs@CS@HA has good biosafety and cell-targeted imaging capability for RF. Based on the successful application of QDs@CS@HA and the mechanism of RF progression in early RF detection, it is expected that QDs@CS@HA may detect RF before the appearance of clinical symptoms.

A nano-delivery system based on preventing degradation and promoting absorption to improve the oral bioavailability of insulin.

Oral insulin delivery can improve patient compliance and simulate the portal-peripheral insulin concentration gradient produced by endogenous insulin, so oral insulin delivery has a broad prospect. However, some characteristics of the gastrointestinal tract, lead to low oral bioavailability. Therefore, a "ternary mutual-assist" nano-delivery system based on poly(lactide-co-glycolide) (PLGA) as the backbone combined with ionic liquids (IL) and vitamin B12-chitosan (VB12-CS) was constructed in this study, the protein protection performance of IL improves the room temperature stability of the loaded insulin during nanocarrier preparation, transportation and storage to a certain extent, and the protein protection function of IL combined with the slow degradation property of PLGA and the pH-responsive function of VB12-CS to prevent the degradation of insulin in the gastrointestinal tract. In addition, the mucosal adhesion function of VB12-CS, VB12 receptor- and clathrin-mediated transcellular transport involving VB12-CS and IL, and paracellular transport mediated by IL and CS can be combined to improve the intestinal epithelial transport efficiency of insulin, thus, the nanocarrier has stronger preventing degradation and promoting absorption effects. Pharmacodynamic studies showed that after oral administration of VB12-CS-PLGA@IL@INS NPs to diabetic mice, the blood glucose level decreased to about 13 mmol/L, below the critical point of 16.7 mmol/L, and the blood glucose reached a normal level, which was 0.4 times of the blood glucose value before administration, its relative pharmacological bioavailability was 31.8 %, higher than the general nanocarriers (10-20 %) and more beneficial to the clinical transformation of oral insulin.

Dumbbell Aptamer Sensor Based on Dual Biomarkers for Early Detection of Alzheimer's Disease.

Finding a timely, sensitive, and noninvasive detection method has become an urgent need for asymptomatic early diagnosis of Alzheimer's disease (AD). MicroRNA-193b (miR-193b) and Aß42 oligomers (AßO42) in neurogenic exosomes were confirmed to reflect pathological changes in the AD early stage. The combination of two biomarkers is promising for the earlier detection of AD. In this study, a detection system based on the principle of the entropy-driven strand displacement reaction (ESDR) was developed, including a dumbbell detection probe (H), an indicator probe (R), and graphene oxide (GO). In the detection system, the two hairpins of H were opened by the interaction of miR-193b (T1) and AßO42 (T2) with the aptamer. Then R hybridized with H and began to displace T, initiating the next round of ESDR to achieve sensitive detection of T. GO specifically adsorbed free R and quenched the fluorescence, further reducing the intensity of the background signal. Both of these points provided the system with a more sensitive analytical performance. The detection limit of miR-193b was 77 pM and the detection limit of AßO42 was 53 pM. This sensor detected the change of "one increase (AßO42) and one decrease (miR-193b)" in the exosome sample. Additionally, results showed that this detection system could distinguish the model of early AD from the non-AD control, which was sufficient for earlier and more sensitive detection of AD. This strategy has strong specificity, high sensitivity, and easy operation, which provides broad prospects for the early diagnosis of AD.