Exosomes are a class of naturally occurring nanoparticles that are secreted endogenously by mammalian cells. Clinical applications for exosomes remain a challenge because of their unsuitable donors, low scalability, and insufficient targeting ability. In this study, we developed a dual-functional exosome-based superparamagnetic nanoparticle cluster as a targeted drug delivery vehicle for cancer therapy. The resulting exosome-based drug delivery vehicle exhibits superparamagnetic behavior at room temperature, with a stronger response to an external magnetic field than individual superparamagnetic nanoparticles. These properties enable exosomes to be separated from the blood and to target diseased cells. In vivo studies using murine hepatoma 22 subcutaneous cancer cells showed that drug-loaded exosome-based vehicle delivery enhanced cancer targeting under an external magnetic field and suppressed tumor growth. Our developments overcome major barriers to the utility of exosomes for cancer application.

No abstract

As an essential component of immunotherapy, monoclonal antibodies (mAbs) have emerged as a class of powerful therapeutics for treatment of a broad range of diseases. For central nervous system (CNS) diseases, however, the efficacy remains limited due to their inability to enter the CNS. A platform technology is reported here that enables effective delivery of mAbs to the CNS for brain tumor therapy. This is achieved by encapsulating the mAbs within nanocapsules that contain choline and acetylcholine analogues; such analogues facilitate the penetration of the nanocapsules through the brain–blood barrier and the delivery of mAbs to tumor sites. This platform technology uncages the therapeutic power of mAbs for various CNS diseases that remain poorly treated.

Down-regulation of microRNA-21 (miR-21) can induce cell apoptosis and reverse drug resistance in cancer treatments. In this study, we explored the most effective schedule of the miR-21 inhibitor (miR-21i) and Temozolomide (TMZ) combined treatment in human glioma cells. Three tumor cell lines, U251 phosphatase and tensin homologue (PTEN) mutant, LN229 (PTEN wild-type), and U87 (PTEN loss of function), were subjected to evaluate the antitumor effects of deigned treatments (a predose of miR-21i for 4/8 h and then a subsequent TMZ treatment, a predose of TMZ for 4/8 h and then a subsequent miR-21i treatment, or a concomitant treatment) in vitro. A synergistic antiproliferative and proapoptotic activity was only obtained in U251 and U87 cells when a predose was administered for 4 h before the treatment of the other therapeutic agent, while the best antitumor effect in LN229 cells was achieved by using the concomitant treatment. Our data indicate that the effect of sequence and timing of administration is dependent on the PTEN status of cell lines. The best suppression effect was achieved by a maximal inhibition of STAT3 and phosphorylated STAT3, in PTEN loss of function cells. Our results reveal that both the sequence and the timing of administration are crucial in glioma combination therapy.

Objective To elucidate the influence of recreational physical activity, body mass index (BMI), and waist circumference on the risk of specific types of urinary incontinence. Study design We conducted a population-based cross-sectional survey in Gansu, China among 2603 women aged 20 years or older. Results The study found that BMI was positively associated with urinary incontinence (P for trend = 0.008) and the association was mainly observed for stress urinary incontinence (OR = 1.4, 95% CI: 1.1, 1.9 for BMI = 24.0–27.9 kg/m2; OR = 2.3, 95% CI: 1.5, 3.6 for BMI ≥ 28.0 kg/m2; P for trend = 0.0005). A positive association between stress incontinence (OR = 1.7, 95% CI: 1.2, 2.5) and waist circumference was observed for women who had waist circumference between 70 cm and 75 cm compared to waist circumference less than 70 cm. Recreational physical activity was inversely associated with overall and mixed urinary incontinence (P for trend <0.0001 for both). A significant interaction between physical activity and waist circumference was found for overall (P = 0.0007) and stress incontinence (P = 0.001). Conclusions The findings that physical activity inversely associated with urinary incontinence and its interaction with waist circumference warrant further investigation, particularly in prospective studies.

The aim of present study is to conceive a biodegradable poly(ethylene glycol)-polylactide (PEG-PLA) copolymer nanoparticle which can be surface biofunctionalized with ligands via biotin-avidin interactions and used as a potential drug delivery carrier targeting to brain glioma in vivo. For this aim, a new method was employed to synthesize biotinylated PEG-PLA copolymers, i.e., esterification of PEG with biotinyl chloride followed by copolymerization of hetero-biotinylated PEG with lactide. PEG-PLA nanoparticles bearing biotin groups on surface were prepared by nanoprecipitation technique and the functional protein transferrin (Tf) were coupled to the nanoparticles by taking advantage of the strong biotin-avidin complex formation. The flow cytometer measurement demonstrated the targeting ability of the nanoparticles to tumor cells in vitro, and the fluorescence microscopy observation of brain sections from C6 glioma tumor-bearing rat model gave the intuitive proof that Tf functionalized PEG-PLA nanoparticles could penetrate into tumor in vivo.

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Hydrogels with injectability and robustness have great promise in clinical practice. However, current injectable hydrogels are usually mechanically weak. Here, an idea, "preformed hydrogel reversion", is proposed to develop robust injectable hydrogels through an intermediate unit-mediated, continuous structural inheritance strategy. In this strategy, robust preformed hydrogels are physically disassembled into intermediate injectable structure-inherited microgels (SIMs), and upon encountering water in physiological environment, the SIMs can construct a macroscopical robust structure with the driving force of hydrogen bonds (H-bonds). The physical disassembly and construction process enables the inheritance of robust structures through SIMs, thereby realizing both excellent injectability and robustness. Beyond that, the SIMs also exhibit long-term storage stability and convenient usability. Using protein drug loading and hemostasis as examples, it is demonstrated that the SIM system shows superiorities in biomedical applications. The proposed idea of "preformed hydrogel reversion" can open new horizons for developing robust injectable hydrogels for diverse applications.