Lixia Long

Blood Exosomes Endowed with Magnetic and Targeting Properties for Cancer Therapy

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.

Sequence-dependent synergistic inhibition of human glioma cell lines by combined temozolomide and miR-21 inhibitor gene therapy.

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.

Development of transferrin functionalized poly(ethylene glycol)/poly(lactic acid) amphiphilic block copolymeric micelles as a potential delivery system targeting brain glioma

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.

Hollow poly(MPC-g-PEG-b-PLA) graft copolymer microcapsule as a potential drug carrier

In this article, an amphiphilic graft copolymer composed of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) as the hydrophilic backbone, poly(L-lactic acid) (PLA) as the hydrophobic side-chains and polyethylene glycol (PEG) as the spacer was synthesized. Transmission electron microscopy revealed that the graft copolymer could self-assemble into hollow microcapsules when dialyzed in aqueous solution and particle sizes ranged from 200 to 300 nm, while the graft copolymer formed core-shell microspheres with the absence of PEG spacer. X-ray photoelectron microscope showed that MPC polymers were located at the surface of the microcapsules. The amounts of adsorbed bovine serum albumin and Fg on the microcapsules were significantly decreased than that on the conventional PLA particles (74% and 60%, respectively), well indicating the anti-adhesive property of the microcapsules. Paclitaxel was chosen as a prototype anticancer drug for the encapsulation and release studies, the results showed that the drug encapsulation efficiency was 89.3 ± 1.2% and the microcapsules exhibited controlled release behaviour.

Thermosensitive elastin-derived polypeptide hydrogels crosslinked by genipin

ABSTRACT In this paper, first, elastin-derived peptides (EPs) with low molecular weight were prepared by acid degradation. Second, elastin-derived peptide hydrogels were fabricated by crosslinking EP with genipin. EP exhibited an inverse transition temperature, and the inverse transition temperature (Tt) could be adjusted by changing the concentration and molecular weight of EP, pH, and adding salt. The freeze-dried EP hydrogels were obviously three-dimensional network structure and the property of EP hydrogel can be optimized by dosage of genipin. Differential scanning calorimetry (DSC) tests and the swelling ratio changing with temperature showed the crosslinked EP hydrogels were still thermosensitive and exhibited a negative swelling behavior. The compression modulus of EP hydrogels can even reach 39.4 kPa, surpassing many other elastin-based hydrogels. This genipin crosslinked EP hydrogel is a good biological material and has great potentiality in tissue engineering. GRAPHICAL ABSTRACT