Bio-inspired synthetic nanovesicles for glucose-responsive release of insulin.

A new glucose-responsive formulation for self-regulated insulin delivery was constructed by packing insulin, glucose-specific enzymes into pH-sensitive polymersome-based nanovesicles assembled by a diblock copolymer. Glucose can passively transport across the bilayer membrane of the nanovesicle and be oxidized into gluconic acid by glucose oxidase, thereby causing a decrease in local pH. The acidic microenvironment causes the hydrolysis of the pH sensitive nanovesicle that in turn triggers the release of insulin in a glucose responsive fashion. In vitro studies validated that the release of insulin from nanovesicle was effectively correlated with the external glucose concentration. In vivo experiments, in which diabetic mice were subcutaneously administered with the nanovesicles, demonstrate that a single injection of the developed nanovesicle facilitated stabilization of the blood glucose levels in the normoglycemic state (<200 mg/dL) for up to 5 days.

ODAM is a predictor for biomedical recurrence and inhibits the migration and invasion of prostate cancer.

Odontogenic ameloblast associated protein (ODAM) is a protein contributed to cell adhesion and has been shown to express in normal prostate tissue, but the expression and significance of ODAM in prostate cancer remain unknown. In this study, we detected the protein expressions of ODAM in 88 prostate cancer tissues with immunohistochemical staining, and found that 53 cases (60.2%) was high expression of ODAM, which was shown in the cytoplasm and paranuclear regions. Furthermore, low expression of ODAM was significantly correlated with lymph node metastasis, preoperative PSA and Gleason score, but not with mean age, follow-up duration, PSM rate and distribution of pathological T stage. Additionally, our results of multivariate analysis showed that low ODAM expression was an independent predictor of biomedical recurrence, while the positive lymph node metastasis, Gleason score, and preoperative PSA were not the independent risks for biomedical recurrence. Overexpression of ODAM did not inhibit the growth of prostate cancer cells PC3, but significant suppressed their invasion and migration with decrease of the protein levels of MMP-2. These results suggest that ODAM is a predictor for biomedical recurrence and inhibits the migration and invasion of prostate cancer.

Spatiotemporal drug delivery using laser-generated-focused ultrasound system.

Laser-generated-focused ultrasound (LGFU) holds promise for the high-precision ultrasound therapy owing to its tight focal spot, broad frequency band, and stable excitation with minimal ultrasound-induced heating. We here report the development of the LGFU as a stimulus for promoted drug release from microgels integrated with drug-loaded polymeric nanoparticles. The pulsed waves of ultrasound, generated by a carbon black/polydimethylsiloxane (PDMS)-photoacoustic lens, were introduced to trigger the drug release from alginate microgels encapsulated with drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. We demonstrated the antibacterial capability of this drug delivery system against Escherichia coli by the disk diffusion method, and antitumor efficacy toward the HeLa cell-derived tumor spheroids in vitro. This novel LGFU-responsive drug delivery system provides a simple and remote approach to precisely control the release of therapeutics in a spatiotemporal manner and potentially suppress detrimental effects to the surrounding tissue, such as thermal ablation.

Novel genipin-collagen immobilization of polylactic acid (PLA) fibers for use as tissue engineering scaffolds.

The material surface plays an important role in the case of biomaterials used as tissue engineering scaffolds. On exposure to a biological environment, extra cellular matrix (ECM) proteins are adsorbed non-specifically onto the surface and cells interact indirectly with the surface through the adsorbed proteins. Most synthetic polymeric biomaterials lack the desirable surface properties for cells as well as have poor cellular adhesion due to their hydrophobic nature. The main objective of this study was to harness surface functionalization technologies to fabricate scaffolds that would be biocompatible and support the adhesion and proliferation of fibroblast cells. The collagen was immobilized on the surface of functionalized PLA via a novel natural cross-linking molecule genipin which resulted in improved cell proliferation of human dermal fibroblasts as compared to the PLA surface coated with collagen without genipin. It is believed that genipin helps reduce steric problems between the functional groups and large protein molecules, and enables immobilized peptide to move more freely in a biological environment.

Stretch-Triggered Drug Delivery from Wearable Elastomer Films Containing Therapeutic Depots.

Mechanical force-based stimulus provides a simple and easily accessible manner for spatiotemporally controlled drug delivery. Here we describe a wearable, tensile strain-triggered drug delivery device consisting of a stretchable elastomer and microgel depots containing drug loaded nanoparticles. By applying a tensile strain to the elastomer film, the release of drug from the microdepot is promoted due to the enlarged surface area for diffusion and Poisson's ratio-induced compression on the microdepot. Correspondingly, both sustained drug release by daily body motions and pulsatile release by intentional administration can be conveniently achieved. Our work demonstrated that the tensile strain, applied to the stretchable device, facilitated release of therapeutics from microdepots for anticancer and antibacterial treatments. Moreover, polymeric microneedles were further integrated with the stretch-responsive device for transcutaneous delivery of insulin and regulation of blood glucose levels of chemically induced type 1 diabetic mice.

Regulation of migration and invasion by Toll-like receptor-9 signaling network in prostate cancer.

Toll-like receptors (TLRs) play an important role in tumorigenesis and progress of prostate cancer. However, the function and mechanism of Toll-like receptor-9 (TLR9) in prostate cancer is not totally understood. Here, we found that high expression of TLR9 was associated with a higher probability of lymph node metastasis and poor prognosis. Further in vitro functional study verified that silence of TLR9 inhibited migration and invasion of PC-3 cells, indicating expression of TLR9 involving in the migration and invasion of cancer cells. The data of microarray exhibited silence of TLR9 induced 205 genes with larger than 2-fold changes in expression levels, including 164 genes down-regulated and 41 genes up-regulated. Functional Gene Ontology (GO) processes annotation demonstrated that the top three scores of molecular and cellular functions were regulation of programmed cell death, regulation of locomotion and response to calcium ion. TLR9 signaling network analysis of the migration and invasion related genes identified several genes, like matrix metallopeptidase 2 (MMP2), matrix metallopeptidase 9 (MMP9), chemokine receptor 4 (CXCR4) and interleukin 8 (IL8), formed the core interaction network based on their known biological relationships. A few genes, such as odontogenic ameloblast-associated protein (ODAM), claudin 2 (CLDN2), gap junction protein beta 1 (GJB1) and Rho-associated coiled-coil containing protein kinase 1 pseudogene 1 (ROCK1P1), so far have not been found to interact with the other genes. This study provided the foundation to discover the new molecular mechanism in signaling networks of invasion and metastasis in prostate cancer.

Resveratrol oligomers for the prevention and treatment of cancers.

Resveratrol (3,4',5-trihydroxystilbene) is a naturally derived phytoalexin stilbene isolated from grapes and other plants, playing an important role in human health and is well known for its extensive bioactivities, such as antioxidation, anti-inflammatory, anticancer. In addition to resveratrol, scientists also pay attention to resveratrol oligomers, derivatives of resveratrol, which are characterized by the polymerization of two to eight, or even more resveratrol units, and are the largest group of oligomeric stilbenes. Resveratrol oligomers have multiple beneficial properties, of which some are superior in activity, stability, and selectivity compared with resveratrol. The complicated structures and diverse biological activities are of significant interest for drug research and development and may provide promising prospects as cancer preventive and therapeutical agents. This review presents an overview on preventive or anticancer properties of resveratrol oligomers.

Ultrasound-triggered regulation of blood glucose levels using injectable nano-network.

The integration of an injectable insulin-encapsulated nano-network with a focused ultrasound system (FUS) can remotely regulate insulin release both in vitro and in vivo. A single subcutaneous injection of the nano-network with intermittent FUS administration facilitates reduction of the blood glucose levels in type 1 diabetic mice for up to 10 d.