Nanosuspensions, as a new drug delivery system for insoluble drugs, are only composed of a drug and a small amount of stabilizer, which is dispersed in an aqueous solution with high drug-loading, small particle size, high dispersion, and large specific surface area. It can significantly improve the dissolution, bioavailability, and efficacy of insoluble drugs. In this study, paclitaxel nanosuspensions ((PTX)NS) were prepared by an ultrasonic precipitation method, with the characteristics of simple preparation and easy repetition. With the help of a homologous targeting mechanism, a kind of glioma C6 cancer cell membrane (CCM)-coated (PTX)NS was developed and modified with ^DWSW peptide to obtain ^DWSW-CCM-(PTX)NS with the functions of BBB penetration and tumor targeting. The results showed that the cancer cell membrane could effectively camouflage the nanosuspensions so that it was not cleared by the immune system and could cross the blood-brain-barrier (BBB) and selectively target tumor tissues. Cell uptake experiments and in vivo imaging confirmed that the uptake of ^DWSW-CCM-(PTX)NS by tumor cells and the distribution in intracranial gliomas increased. Cytotoxicity test and in vivo anti-glioma studies showed that ^DWSW-CCM-(PTX)NS could significantly inhibit the growth of glioma cells and significantly prolong the survival time of glioma-bearing mice. Finally, the cancer cell membrane coating endowed the nanosuspensions with the biological properties of homologous adhesion and immune escape. This study provides an integrated solution for improving the targeting of nanosuspensions and demonstrates the encouraging potential of biomimetic nanosuspensions applicable to tumor therapy.

A kind of N-containing borate ester (DEBE) with a double five-member-ring structure as a lubricant additive was synthesized by using boric acid, diethanolamine and alkylphenol polyoxyethylene ether as the starting materials.

Apolipoprotein E4 (ApoE4) is the main genetic risk factor for Alzheimer’s disease (AD), but the exact way in which it causes AD remains unclear. Curcumin is considered to have good therapeutic potential for AD, but its mechanism has not been clarified. This study aims to observe the effect of curcumin on ApoE4 transgenic mice and explore its possible molecular mechanism. Eight-month-old ApoE4 transgenic mice were intraperitoneally injected with curcumin for 3 weeks, and the Morris water maze test was used to evaluate the cognitive ability of the mice. Immunofluorescence staining, immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay (ELISA) were used to examine the brain tissues of the mice. Curcumin reduced the high expression of ApoE4 and the excessive release of inflammatory factors in ApoE4 mice. In particular, the expression of marker proteins of endoplasmic reticulum (ER) stress was significantly increased in ApoE4 mice, while curcumin significantly reduced the increase in the expression of these proteins. Collectively, curcumin alleviates neuroinflammation in the brains of ApoE4 mice by inhibiting ER stress, thus improving the learning and cognitive ability of transgenic mice.

Radiation-induced brain injury (RIBI) is a serious adverse effect of radiotherapy. RIBI has garnered considerable clinical attention owing to its powerful effects on brain function and cognition; however, no effective treatment is available. The microbiota-gut-brain axis theory is a novel concept of treating RIBI by regulating gut microbiota. Quercetin, a particularly common flavonoid compound, has a wide range of biological activities and can regulate gut microbiota; however, it has poor solubility and dispersibility. In the present study, oral gels of inclusion complex comprising quercetin and HP-β-CD were prepared, which increased quercetin dispersion and extended its release time in the intestinal tract. First, the relative abundance and diversity of gut microbiota in RIBI mice changed after oral administration of quercetin inclusion complex gels (QICG). Second, the spontaneous activity behavior and short-term memory ability as well as anxiety level were improved. Third, changes in physical symptoms were observed, including a decrease in TNF-α and IL-6 levels. H&E staining revealed that gut epithelial injury and intestinal inflammation as well as hippocampal inflammation were ameliorated. Antibiotics treatment (Abx) mice were developed to disrupt the mice's original gut microbiota composition. No significant improvement was observed in behavior or histopathology after oral administration of QICG in Abx mice of RIBI, indicating that the effect of QICG on improving RIBI was regulated by intestinal microbiota. Finally, the QICG preparation is efficient, exerting a protective effect on RIBI by regulating gut microbiota via the microbiota-gut-brain axis, which provides a novel idea for RIBI treatment.

Stimuli-responsive drug delivery systems (DDSs) are expected to realize site-specific drug release and kill cancer cells selectively. In this study, a pH-responsive micelle was designed utilizing the pH-sensitivity of borate bonds formed between dopamine and boronic acid. First, methyl (polyethylene glycol)-block-polycaprolactone (mPEG-PCL) was conjugated with 4-cyano-4-(thiobenzoylthio)pentanoic acid (CTP) to obtain a macroinitiator. Two different segments poly(dopamine methacrylamide) (PDMA) and poly(vinylphenylboronic acid) (PVBA) were then grafted to the end of mPEG-PCL. Two triblock copolymers, mPEG-PCL-PDMA and mPEG-PCL-PVBA, were then obtained by reversible addition–fragmentation transfer (RAFT) polymerization. These copolymers and their mixture self-assembled in aqueous solution to form micelles that were able to load hydrophobic anticancer drug doxorubicin (DOX). These two-component micelles were found to be pH-sensitive, in contrast to the one-component micelles. Furthermore, MTT studies showed that the micelles were almost nontoxic. The DOX-loaded micelles showed cytotoxicity equivalent to that of DOX at high concentration. In vivo antitumor experiments showed that this pH-sensitive polymeric micellar system had an enhanced therapeutic effect on tumors. These two-component boronate-based pH micelles are universally applicable to the delivery of anticancer drugs, showing great potential for cancer therapy.