Glucose-responsive insulin delivery systems, which can maintain a stable level of blood glucose, have been proposed as a promising method to treat diabetes. Such systems can reduce potential toxicity and enhance patient compliance compared to traditional therapies. Accordingly, we designed a mesoporous silica nanoparticle (MSN)-based glucose-sensitive and self-regulated drug release system to achieve the goal of long circulation and "touch switch" in vivo. In this system, carboxyphenylboronic acid (CPBA) was first modified on the surface of MSN using amidation reaction. Insulin (INS) was then loaded in the channels of MSN (CPBA-MSN/INS) through physical adsorption, and sodium alginate (SA) was introduced onto the surface of the CPBA-MSN/INS nanoparticles as the gatekeeper via amidation reaction (SA/CPBA-MSN/INS). We found the drug loading capacity of INS was 261 mg/g. In the normal range of blood glucose, INS was scarcely released due to the reversible covalent interaction between 1,2-diols of SA and CPBA. Within the high concentration of glucose, the boronate esters could be dissociated, which results in the mesoporous channels opening and the release of INS. In vivo experiments on diabetic mice showed SA/CPBA-MSN/INS sustained a normal blood glucose level for up to 12 h with a single dose. Moreover, the lipid metabolism disorder and organ damage of diabetic mice were alleviated after treatment with SA/CPBA-MSN/INS. Therefore, SA/CPBA-MSN/INS characterized by an "on-off" regulated drug release property and high biosafety shows promise for applications in diabetes treatment.

Therapeutic strategies based on modulation of microRNAs (miRNAs) activity hold much promise for cancer therapy, but for clinical applications, the effi cient delivery of miRNAs to tumor cells or tumor tissues remains a great challenge. In this work, microRNA-181b inhibitor (anti-miR-181b) is successfully condensed into polyethyleneimine (PEI)-modifi ed and folate receptor (FR)-targeted PEGylated gold nanocages (AuNCs). This delivery system is designated as anti-miR-181b/PTPAuNCs nanocomplexes (PTPAuNC-NPs), which begin with chemical modifi cation of AuNCs with SH-PEG 5000 -folic acid (SH-PEG 5000 -FA) and SH-PEG 5000 through a gold-sulfur bond, followed by conjugating PEI using lipoic acid as a linker. Finally anti-miR-181b is condensed via electrostatic interactions. In vitro and in vivo experiments show that PTPAuNC-NPs can effi ciently deliver anti-miR-181b into target sites to suppress tumor growth, and considerably decrease tumor volumes in SMMC-7721 tumor-bearing nude mice under near-infrared radiation. All these results suggest that PTPAuNC-NP gene delivery system with combination of gene therapy and photothermal therapy will be of great potential use in future cancer therapy.

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The pharmacokinetic characteristics of the three PPIs are significantly dependent on the CYP2C19 genotype status. These data indicate that individualized dose regimen of the three PPIs, based on identification of genotype, can be of great benefit for ensuring the reasonable use of these drugs.

Heat stress is exacerbated by global warming and affects human and animal health, leading to heart damage caused by imbalances in reactive oxygen species (ROS) and the antioxidant system, acid-base chemistry, electrolytes and respiratory alkalosis. Vitamin C scavenges excess ROS, and sodium bicarbonate maintains acid-base and electrolyte balance, and alleviates respiratory alkalosis. Herein, we explored the ability of vitamin C alone and in combination with equimolar sodium bicarbonate (Vitamin C-Na) to stimulate endogenous antioxidants and heat shock proteins (HSPs) to relieve heat stress in H9C2 cells. Control, vitamin C (20 μg/ml vitamin C for 16 h) and vitamin C-Na (20 μg/ml vitamin C-Na for 16 h) groups were heat-stressed for 1, 3 or 5 h. Granular and vacuolar degeneration, karyopyknosis and damage to nuclei and mitochondria were clearly reduced in treatment groups, as were apoptosis, lactate dehydrogenase activity and ROS and malondialdehyde levels, while superoxide dismutase activity was increased. Additionally, CRYAB, Hsp27, Hsp60 and Hsp70 mRNA levels were upregulated at 3 h (p < 0.01), and protein levels were increased for CRYAB at 0 h (p < 0.05) and 1 h (p < 0.01), and for Hsp70 at 3 and 5 h (p < 0.01). Thus, pre-treatment with vitamin C or vitamin C-Na might protect H9C2 cells against heat damage by enhancing the antioxidant ability and upregulating CRYAB and Hsp70.