Macrophage Membrane-Modified MoS2 Quantum Dots as a Nanodrug for Combined Multi-Targeting of Alzheimer's Disease.

The complex pathological mechanism of Alzheimer's disease (AD) limits the efficacy of simple drug therapy, and drugs are difficult to penetrate the blood-brain barrier (BBB). Therefore, it is a breakthrough to enhance the therapeutic effect of AD by rationally using multiple therapeutic strategies to inhibit multiple pathological targets. In this study, macrophage membrane (MM) with active targeting inflammation function is used to functionalize molybdenum disulfide quantum dots (MoS2 QDs) with the properties of elimination of reactive oxygen species (ROS) and anti-Aß1-42 deposition to form the nano drug (MoS2 QDs/MM), and play the role of multi-target combined therapy with NIR. The results show that MoS2 QDs/MM has a targeted therapeutic effect on ROS elimination and anti-deposition of Aß1-42 . In addition, the combined therapy group effectively reduced Aß1-42 mediated cytotoxicity. The modification of MM could effectively target the brain, and NIR irradiation could actively increase the cross of BBB of materials. In vivo behavioral study also show that APP/PS1 mice in the combined treatment group showed the similar exploration desire and learning ability to mice in the group of WT. MoS2 QDs/MM is an excellent nano drug with multiple effects, which has advantages in the field of neurological diseases with crisscross pathogenesis.

Macrophage membrane-encapsulated nitrogen-doped carbon quantum dot nanosystem for targeted treatment of Alzheimer's disease: Regulating metal ion homeostasis and photothermal removal of ß-amyloid.

The abnormal aggregation of ß-amyloid protein (Aß) is a major contributor to Alzheimer's disease (AD). Cu2+ homeostasis imbalance can lead to the aggregation of Aß, resulting in cytotoxic oligomers and fibrous aggregates, causing neuroinflammation and nerve cell damage, ultimately leading to AD. In this study, we synthesized nitrogen-doped carbon quantum dot (CQD), and designed a macrophage membrane (RAW-M) encapsulated CQD nanosystem for the first time. The abundant nitrogen-containing groups on the surface of CQD effectively capture excess Cu2+ and inhibit rapid Aß aggregation. Additionally, the good photothermal properties of CQD dissolve the formed fiber precipitates under near-infrared light (NIR). In vitro and in vivo studies showed that the nanosystem significantly improved BBB permeability under laser irradiation, enhancing its ability to cross the BBB and overcome traditional anti-AD drug limitations. In vivo investigations conducted on APP/PS1 mice indicate that the nanosystem strongly reduced Aß deposition, mitigated neuroinflammation, and ameliorates deficits in learning and memory. Overall, our nanocarrier approach adjusts metal ion homeostasis, inhibits abnormal Aß aggregation, and uses excellent photothermal properties to depolymerize mature Aß fibrils to protect cells from Aß neurotoxicity, providing an effective strategy for Aß-targeted treatment of AD.

An erythrocyte membrane-camouflaged biomimetic nanoplatform for enhanced chemo-photothermal therapy of breast cancer.

Nano drug delivery systems are a research hotspot in the field of tumor therapy. In this work, molybdenum disulfide (MoS2) nanosheets were selected as the base material and a natural red blood cell membrane (RBC membrane) was camouflaged on the nanosheets to enhance their dispersibility and tumor targeting profile. The camouflaged molybdenum disulfide nanocomposites (MoS2-RBC) were successfully prepared by incubation. This nanomaterial has good stability and biocompatibility with a good immune evasion ability. MoS2 has a large specific surface area and unique layered structure, which provides favorable conditions for the loading of anticancer drugs. Adriamycin hydrochloride (DOX) was used as the model drug and the drug loading capacity was 98.98%. In the tumor microenvironment, the red cell membrane modified MoS2 drug delivery system (MoS2-RBC-DOX) showed obvious pH-dependent release behavior. In addition, the excellent photothermal properties of MoS2 are conducive to the release of drugs, thus improving the efficacy. According to the cell tests, MoS2-RBC had no cytotoxicity toward tumor cells, while DOX loading induced dose-dependent cytotoxicity. Furthermore, MoS2-RBC has a favorable photothermal effect, and chemotherapy combined with photothermal therapy is more effective than any single therapy. In vivo fluorescence imaging and in vivo photothermal imaging experiments confirmed the promoted accumulation of carrier materials at the tumor site after RBC membrane modification. Finally, in vivo antitumor studies showed that photothermal/chemotherapy combined with MoS2-RBC could completely inhibit tumor growth, and the body weights of mice fluctuated within the normal range without significant decrease. In summary, this MoS2-RBC drug delivery system provides a safe, rapid and effective option for future treatment of breast cancer.