Exosomes (Exo) hold great promise as endogenous nanocarriers that can deliver biological information between cells. However, Exo are limited in terms of their abilities to target specific recipient cell types. We developed a strategy to isolate Exo exhibiting increased binding to integrin α v β 3 . Binding occurred through a modified version of a disintegrin and metalloproteinase 15 (A15) expressed on exosomal membranes (A15-Exo), which facilitated co-delivery of therapeutic quantities of doxorubicin (Dox) and cholesterol-modified miRNA 159 (Cho-miR159) to triple-negative breast cancer (TNBC) cells, both in vitro and in vivo. The targeted A15-Exo were derived from continuous protein kinase C activation in monocyte-derived macrophages. These cell-derived Exo displayed targeting properties and had a 2.97-fold higher production yield. In vitro, A15-Exo co-loaded with Dox and Cho-miR159 induced synergistic therapeutic effects in MDA-MB-231 cells. In vivo, miR159 and Dox delivery in a vesicular system effectively silenced the TCF-7 gene and exhibited improved anticancer effects, without adverse effects. Therefore, our data demonstrate the synergistic efficacy of co-delivering miR159 and Dox by targeted Exo for TNBC therapy.

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The aim of this study was to investigate the suitability of poly-(d,l-lactic acid-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA triblock copolymer as a matrix material for a sustained-release system for docetaxel (DTX). The copolymers were synthesized by ring-opening polymerization reaction and characterized by (1)H-NMR and gel permeation chromatography. The DTX-loaded formulations were prepared, characterized. And the antitumor efficacy and the pharmacokinetics of DTX-loaded copolymer on A-549 lung tumor-bearing BALB/cA mice were investigated. The results showed that DTX-loaded copolymer highly increased the solubility of DTX by more than 3000-fold. And copolymer concentration as well as drug loading level exerted appreciable influence on the drug release behavior. Further, the pharmacokinetic test showed that DTX-loaded copolymer could be with the sustained-release nature for over 3 weeks, which correlated well with the in vitro release. Additionally, one intratumoral injection of the thermo-sensitive hydrogel containing DTX was comparable to three intravenous injections of DTX injection in inhibiting the tumor growth in A-549 lung tumor-bearing BALB/cA mice with a less toxic manner. PLGA-PEG-PLGA could thus provide a promising alternate locally delivered vehicle for DTX to achieve prolonged exposure having greater efficacy in inhibiting tumor growth with lower toxicity.

20(R)-ginsenoside Rg3 (20(R)-Rg3) has shown multiple pharmacological activities and been considered as one of the most promising approaches for fatigue treatment. However, 20(R)-Rg3 has a low bioavailability after oral administration in human due to the first-pass effect. Recently, nasal route has gained increasing interest as it can avoid first-pass effect for its lower enzymatic activity compared with the gastrointestinal tract and liver. In order to provide an animal experimental evidence of 20(R)-Rg3 intranasal administrated preparation, the antifatigue effect of 20(R)-Rg3 after intranasal administration was investigated. Two weeks after 20(R)-ginsenoside Rg3 was administrated intranasally to mice at three different doses, the anti-fatigue effect of 20(R)-Rg3 was evaluated by the weight-loaded swimming test and biochemical parameters related to fatigue, such as serum urea nitrogen (SUN), lactic dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), blood lactic acid (LA) and hepatic glycogen. The results showed that compared with the negative control group, the intermediate-dose and the high-dose groups significantly prolonged the weight-loaded swimming time (pϽ0.05; pϽ0.01), and also increased the hepatic glycogen levels (pϽ0.05); SUN levels were decreased considerably in three 20(R)-Rg3-treated groups (pϽ0.01). In addition, the low-dose group obviously decreased the content of blood LA (pϽ0.05). However, the levels of LDH, SOD and MDA did not show a significant change. Our results predicted a benefit of 20(R)-Rg3 as an anti-fatigue treatment by intranasal administration. The mechanism was related to the increase of the storage of hepatic glycogen, and the decrease of the accumulation of metabolite such as lactic acid and serum urea nitrogen.