Chaoyong Liu

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.

Efficient delivery of therapeutic miRNA nanocapsules for tumor suppression.

miRNA nanocapsules are synthesized with enhanced stability for miRNA delivery with high transduction efficiency, offering a novel class of miRNA vectors for cancer therapy.

ICAT inhibits glioblastoma cell proliferation by suppressing Wnt/β-catenin activity

Inhibitor of β-catenin and T-cell factor (ICAT) is a key component of Wnt/β-catenin signaling. ICAT blocks the formation of the β-catenin/TCF complex and has been demonstrated to be involved in embryonic development and carcinogenesis. As an inhibitor of canonical Wnt signaling, ICAT was presumed to be a tumor-suppressor gene. However, the ICAT functions in human glioma remain unknown. In this study, we evaluated the expression of ICAT in 305 human glioma tissues and found that negative ICAT expression correlated with higher grade glioma and poor survival in patients with glioma. Then we transfected glioma cells with ICAT plasmid. Western blotting showed an increased ICAT protein expression level in glioma cells. MTT assay, flow cytometry and cell invasion assay were used to detect cell proliferation, cell cycle distribution, apoptosis and invasion. Our studies confirmed that ICAT inhibits glioma cell proliferation and invasion, and it induces cell apoptosis and cell cycle progression arrest. Besides, ICAT slowed down tumor growth in a glioblastoma xenograft model. Therefore, our study demonstrates that ICAT may serve as a tumor-suppressor in human glioma suggesting a promising direction for targeting therapy in glioma.

Aspirin-/TMZ-coloaded Microspheres Exert Synergistic Antiglioma Efficacy via Inhibition of β-catenin Transactivation

Currently temozolomide (TMZ) as a potent agent is widely used to treat the glioblastoma multiforme (GBM), whereas recurrence due to intrinsic or acquired therapeutic resistance often occurs. Combination chemotherapy with TMZ may be a promising therapeutic strategy to improve treatment efficacy.

Surface Functionalization of Titanium Alloy with miR-29b Nanocapsules To Enhance Bone Regeneration

Titanium and its alloys have been widely used over the past 3 decades as implants for healing bone defects. Nevertheless, the bioinert property of titanium alloy limits its clinical application and surface modification method is frequently performed to improve the biological and chemical properties. Recently, the delivery of microRNA with osteogenesis capability has been recognized as a promising tool to enhance bone regeneration of implants. Here, we developed a biodegradable coating to modify the titanium surface in order to enhance osteogenic bioactivity. The previous developed nanocapsules were used as the building blocks, and then a bioactive titanium coating was designed to entrap the miR-29b nanocapsules. This coating was not only favorable for cell adhesion and growth but also provided sufficient microRNA transfection efficacy and osteoinductive potential, resulting in a significant enhancement of bone regeneration on the surface of bioinert titanium alloy.

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.

An injectable miRNA-activated matrix for effective bone regeneration in vivo

The delivery of miRNAs that can promote osteogenic differentiation may be promising for bone regeneration. However, low transfection efficiency into cells, especially stem cells, limits in vivo applications. Thus, an injectable miRNA in situ delivery system was designed. miRNAs were encapsulated within nanocapsules which were further entrapped into an O-carboxymethyl chitosan (CMCS) network via electrostatic interactions. In this miRNA-activated matrix system, miRNAs were encapsulated within the polymer shells rather than physically adsorbed onto the surface to avoid leakage of miRNA and offer better stability for cell transfection. microRNA-21 (miR-21) is an osteogenic-related miRNA and it is chosen as the gene model in the current study. Delivery of miR-21 nanocapsules by CMCS significantly promoted the osteogenic differentiation of human umbilical cord mesenchymal stem cells (hUMSCs) as evidenced by up-regulation of osteogenic markers such as alkaline phosphatase (ALP) and runt-related transcription factor 2 (RUNX-2). Also the delivery system promoted bone formation (2.4-fold, p < 0.05) compared to controls. Thus, the current strategy provides not only substantial miRNA protection and better cell transfection efficacy but also has a biodegradable microenvironment with local and sustained gene release, which significantly enhances bone regeneration in vivo.