A Rapidly and Highly Self-Healing Poly(Sulfobetaine Methacrylate) Hydrogel with Stretching Properties, Adhesive Properties, and Biocompatibility.

This study focuses on the preparation of stretchable zwitterionic poly(sulfobetaine methacrylate) (PSBMA) hydrogels. To address the weak mechanical properties of chemically crosslinked PSBMA hydrogels, a physical crosslinking method utilizing hydrophobic interactions to crosslink hydrogels to approach tough properties is developed. Here, sodium dodecyl sulfate (SDS)-based micelle is used as a physical crosslinker to prepare physically crosslinked PSBMA (PSBMAphy ) hydrogels, and ethylene glycol dimethylacrylate (EGDMA) is used to prepare a control group of chemically crosslinked PSBMA (PSBMAchem ) hydrogels. The mechanical properties of the two hydrogels are compared, and PSBMAphy hydrogels exhibit greater flexibility than the PSBMAchem hydrogels. When the PSBMAphy hydrogels are subjected to external forces, the micelles act as dynamic crosslinking sites, allowing the stress to disperse and prevent the hydrogel from breaking. In addition, the PSBMAphy hydrogels have nearly 100% self-healing properties within 2.5 min. The PSBMAphy hydrogels exhibit usable adhesive properties to porcine skin and subcutis. MTT and hemolysis tests show that the PSBMAphy hydrogels have excellent biocompatibility and hemocompatibility. This study proposes that the multifunctional PSBMAphy hydrogels with micelles will be potential to carry drugs for use in drug delivery systems in the future.

Phytochemical naphtho[1,2-b] furan-4,5­dione induced topoisomerase II-mediated DNA damage response in human non-small-cell lung cancer.

BACKGROUND: Phytochemical naphtho[1,2-b] furan-4,5­dione (NFD) presenting in Avicennia marina exert anti-cancer effects, but little is known regarding about DNA damage-mediated apoptosis in non-small-cell lung carcinoma (NSCLC). PURPOSE: To examine whether NFD-induced apoptosis of NSCLC cells is correlated with the induction of DNA damage, and to investigate its underlying mechanism. STUDY DESIGN: The anti-proliferative effects of NFD were assessed by MTS Assay Kit FACS assay, and in vivo nude mice xenograft assay. The DNA damage related proteins, the Bcl-2 family and pro-apoptotic factors were examined by immunofluorescence assay, q-PCR, and western blotting. The activity of NF-κB p65 in nuclear extracts was detected using a colorimetric DNA-binding ELISA assay. The inhibitory activity of topoisomerase II (TOPO II) was evaluated by molecular docking and TOPO II catalytic assay. RESULTS: NFD exerted selective cytotoxicity against NSCLC H1299, H1437 and A549 cells rather than normal lung-embryonated cells MRC-5. Remarkably, we found that NFD activated the hull marker and modulator of DNA damage repairs such as γ-H2AX, ATM, ATR, CHK1, and CHK2 probably caused by the accumulation of intracellular reactive oxygen species (ROS) and inhibition of TOPO II activity. Furthermore, the suppression of transcription factor NF-κB by NFD resulted in significantly decreased levels of pro-survival proteins including Bcl-2 family Bcl-2, Bcl-xL and Mcl-1 and the endogenous inhibitors of apoptosis XIAP and survivin in H1299 cells. Moreover, the nude mice xenograft assay further validated the suppression of H1299 growth by NFD, which is the first report for evaluating the anti-cancer effect of NFD in vivo. CONCLUSION: These findings provide a novel mechanism indicating the inhibition of TOPO II activity and NF-κB signaling by NFD, leading to DNA damage and apoptosis of NSCLC tumor cells.

Aptamer-functionalized gold nanoparticles as photoresponsive nanoplatform for co-drug delivery.

Various platforms have been developed as innovative nanocarriers to deliver therapeutic agents to the diseased sites. Multifunctional surface modification allows an enhanced recognition and uptake of drug carriers by targeted cells. However, the development of drug resistance in some tumor cells plays a major role in the failure of chemotherapy. Drugs given in combination, called multidrug delivery approach, was designed to improve the therapeutic efficacy and has become an increasingly used strategy that is of great importance in clinical cancer treatments. In this study, aptamer-functionalized gold nanoparticles (Au NPs) have been used as a nanoplatform to codeliver two different anticancer drugs for improving the drug effectiveness. The surface of Au NPs (13 nm in diameter) was assembled with AS1411 aptamers, which tethered with 21-base pairs of (CGATCGA)3 sequence approached to the Au NPs. Both the photosensitizer 5,10,15,20-tetrakis(1-methylpyridinium-4-yl) porphyrin (TMPyP4) and the chemotherapeutic drug doxorubicin (Dox) were then physically attached to the AS1411-conjugated Au NPs (T/D:ds-NPs) and delivered to the target tumor cells such as HeLa and Dox-resistant MCF-7R cell lines. When exposed to a 632 nm light, reactive oxygen species induced by TMPyP4 molecules were generated inside the living cells, followed by cell damage. In addition, triggered release of the complementary drugs also occurred simultaneously during the photodynamic reaction. In the presence of Dox molecules, the toxicity toward the target cells was superior to individual drug treatment. Overall, a co-drug delivery platform was successfully established to improve the therapeutic efficacy in tumor cells. The improvement of the photodynamic-stimulated triggered release was enhanced, thus highly promising precise drug release in targeted drug delivery.

Relationship of blood pressure control and hospitalization risk to medication adherence among patients with hypertension in Taiwan.

BACKGROUND: Despite the efficacy of antihypertensive treatment in preventing cardiovascular complications, there are often problems with medication adherence in hypertensive patients. The objective of this study was to examine the medication adherence and its association with blood pressure (BP) control, cardiovascular disease (CVD) hospitalization, and all-cause hospitalization. METHODS: We conducted a retrospective cohort observation of patients who were treated for hypertension from January 2005 to December 2006. Medical and pharmacy claims were obtained from Taiwan's National Health Insurance (NHI) database, whereas electronic records, including demographic characteristics and clinical information, were retrieved from a disease management program. To determine the degree of medication adherence, we calculated the proportion of days covered (PDC) by filled prescriptions. The associations of medication adherence with BP control, CVD hospitalization, and all-cause hospitalization were examined using multiple logistic regression models. RESULTS: The study subjects comprised a total of 29,685 hypertensive patients. Of which, 40.1% of the patients had hypertension history of >5 years and 39.7% of patients had some comorbidity. In total, 85.5% of patients were categorized as adherent, with PDC >or=80; 60% of adherent patients had good BP control. Poor medication adherence was associated with poor BP control (odds ratio (OR) = 1.20, 1.13-1.29), CVD hospitalization (OR = 1.43, 1.14-1.81), and all-cause hospitalization (OR = 1.47, 1.21-1.78). CONCLUSION: Our observation study clearly indicates that lower medication adherence is associated with poor BP control and higher risk of CVD and all-cause hospitalization in hypertensive patients.