Hongsuk Suh

Poly(PEGA)-b-poly(l-lysine)-b-poly(l-histidine) Hybrid Vesicles for Tumoral pH-Triggered Intracellular Delivery of Doxorubicin Hydrochloride

A series of poly(ethylene glycol) methyl ether acrylate-block-poly(L-lysine)-block-poly(L-histidine) [p(PEGA)30-b-p(Lys)25-b-p(His)n] (n = 25, 50, 75, 100) triblock copolypeptides were designed and synthesized for tumoral pH-responsive intracellular release of anticancer drug doxorubicin hydrochloride (Dox). The tumoral acidic pH-responsive hybrid vesicles fabricated were stable at physiological pH 7.4 and could gradually destabilize in acidic pH as a result of pH-induced swelling of the p(His) block. The blank vesicles were nontoxic over a wide concentration range (0.01-100 μg/mL) in normal cell lines. The tumor acidic pH responsiveness of these vesicles was exploited for intracellular delivery of Dox. Vesicles efficiently encapsulated Dox, and pH-induced destabilization resulted in the controlled and sustained release of Dox in CT26 murine cancer cells, and dose-dependent cytotoxicity. The tumor-specific controlled release Dox from vesicles demonstrates this system represents a promising theranostic agent for tumor-targeted delivery.

Dual Stimuli-Responsive Vesicular Nanospheres Fabricated by Lipopolymer Hybrids for Tumor-Targeted Photodynamic Therapy

Smart delivery system of photosensitizer chlorin e6 (Ce6) has been developed for targeted photodynamic therapy (PDT). Simple self-assemblies of the mixtures comprising soybean lecithin derived phosphatidylcholine (PC), phosphatidylethanolamine-poly(L-histidine)40 (PE-p(His)40), and folic acid (FA) conjugated phosphatidylethanolamine-poly(N-isopropylacrylamide)40 (PE-p(NIPAM)40-FA) in different ratios yield smart nanospheres characterized by (i) stable and uniform particle size (∼100 nm), (ii) positive surface charge, (iii) high hydrophobic drug (Ce6) loading efficiency up to 45%, (iv) covalently linked targeting moiety, (v) low cytotoxicity, and (vi) smartness showing p(His) block oriented pH and p(NIPAM) oriented temperature responsiveness. The Ce6-encapsulated vesicular nanospheres (Ce6@VNS) were used to confirm the efficiency of cellular uptake, intracellular distribution, and phototoxicity against KB tumor cells compared to free Ce6 at different temperature and pH conditions. The Ce6@VNS system showed significant photodynamic therapeutic efficiency on KB cells than free Ce6. A receptor-mediated inhibition study proved the site-specific delivery of Ce6 in targeted tumor cells.

Hierarchically nanostructured carbon-supported manganese oxide for high-performance pseudo-capacitors

We developed 3-D network carbon materials by directly pyrolyzing as-prepared polynaphthalene (PNT). The PNT-based materials were synthesized from chloromethylated naphthalene and were self-polymerized using anhydrous aluminum chloride as the Friedel-Crafts catalyst and chloromethyl methyl ether as a crosslinker. The micro-, meso-, and macroporous 3-D carbon materials showed large specific surface areas, large electrolyte-electrode interface areas, and continuous electron transport paths. MnO2/carbon composites were then synthesized by chemically depositing MnO2 onto the carbon substrate surfaces through a self-limiting redox reaction between KMnO4 solution and carbon substrates, producing high-performance pseudo-capacitor electrodes. The unique electrode architecture demonstrated high capacitance up to 286.8 F g-1, and good cycling stability up to 1000 cycles without losing its capacitance. The electrode shows potential applications for the development of high-performance supercapacitors for a variety of power-demanding devices.

Efficient, Solvent-Free, Multicomponent Method for Organic-Base-Catalyzed Synthesis of β-Phosphonomalonates

An efficient, one-pot, di-n-butylamine-catalyzed, three-component synthesis of β-phosphonomalonates has been developed. A wide range of substrates, including aromatic and fused aromatic aldehydes, were condensed with enolizable C-H activated compounds and dialkylphosphites to give the desired products in excellent yields. This method provides an eco-friendly alternative approach to rapid construction of a diversity-oriented library of β-phosphonomalonates.

Resveratrol analogue, HS-1793, induces apoptotic cell death and cell cycle arrest through downregulation of AKT in human colon cancer cells

Resveratrol, a polyphenolic compound, is a naturally occurring phytochemical and is found in a variety of plants, including grapes, berries and peanuts. It has gained much attention for its potential anticancer activity against various types of human cancer. However, the usefulness of resveratrol as a chemotherapeutic agent is limited by its photosensitivity and metabolic instability. In this study the effects of a synthetic analogue of resveratrol, HS-1793, on the proliferation and apoptotic cell death were investigated using HCT116 human colon cancer cells. Although this compound has been reported to have anticancer activities in several human cancer cell lines, the therapeutic effects of HS-1793 on human colon cancer and its mechanisms of action have not been extensively studied. HS-1793 inhibited cell growth and induced apoptotic cell death in a concentration-dependent fashion. Induction of apoptosis was determined by morphological changes, cleavage of poly(ADP-ribose) polymerase, alteration of Bax/Bcl-2 expression ratio, and caspase activations. Flow cytometric analysis revealed that HS-1793 induced G2/M arrest in the cell cycle progression in HCT116 cells. Furthermore, HS-1793 showed more potent anticancer effects in several aspects than resveratrol in HCT116 cells. In addition, HS-1793 suppressed Akt and the phosphatidylinositol-3 kinase/Akt inhibitor LY294002 was found to enhance its induction of apoptosis. Thus, these findings suggest that HS-1793 have potential as a candidate chemotherapeutic agent against human colon cancer.

Synthesis and Properties of Copolymer with Carbazole and F-Quinoxaline Units for OPVs

A new accepter unit, 6,7-difluoro-2,3-dihexylquinoxaline, was prepared and utilized for organic photovoltaics. The solid film of the synthesized conjugated polymer, poly[N-9-heptadecanyl-2,7-carbazole-alt-5,8-(6,7-difluoro-2,3-dihexyl-5,8-di(thiophen-2-yl) quinoxaline)] (PCDTQxF), shows absorption band with maximum peak at about 502 nm and the absorption onset at 580 nm, corresponding to band gap of 2.14 eV. The oxidation onset of the PCDTQxF was estimated to be 0.67 V, which correspond to HOMO energy level of −5.47 eV. The deep HOMO energy level of PCDTQxF leads to higher VOC. The device of PCDTQxF:PC71BM (1:1) showed VOC of 0.80 V, JSC of 2.41 mA/cm2, and FF of 0.37, giving PCE of 0.7%.

HS-1793, a resveratrol analogue, downregulates the expression of hypoxia-induced HIF-1 and VEGF and inhibits tumor growth of human breast cancer cells in a nude mouse xenograft model

A synthetic analogue of resveratrol, 4-(6-hydroxy-2-naphtyl)-1,3-benzenediolxa0(HS-1793), with improved photosensitivity and stability profiles, has been recently reported to exert anticancer activity on various cancer cells. However, the molecular mechanism of action and inxa0vivo efficacy of HS-1793 in breast cancer cells have not been fully investigated. In the present study, we evaluated the effect of HS-1793 on hypoxia-inducible factor-1αxa0(HIF-1α), which drives angiogenesis and the growth of solid tumors, in addition to the inxa0vivo therapeutic effects of HS-1793 on breast cancer cells. HS-1793 was found to inhibit hypoxia (1.0% oxygen)-induced HIF-1α expression at the protein level, and its inhibitory effect was more potent than that of resveratrol in MCF-7 and MDA-MB-231 breast cancer cells. Furthermore, HS-1793 reduced the secretion and mRNA expression of vascular endothelial growth factorxa0(VEGF), a key mediator of HIF-1-driven angiogenesis, without affecting cell viability. To evaluate the anticancer effects of HS-1793 inxa0vivo, triple-negative MDA-MB-231 breast cancer xenografts were established in nude mice. HS-1793 significantly suppressed the growth of breast cancer tumor xenografts, without any apparent toxicity. Additionally, decreases in Ki-67, a proliferation index marker, and CD31, a biomarker of microvessel density, were observed in the tumor tissue. Expression of HIF-1 and VEGF was also downregulated in xenograft tumors treated with HS-1793. These inxa0vivo results reinforce the improved anticancer activity of HS-1793 when compared with that of resveratrol. Overall, the present study suggests that the synthetic resveratrol analogue HS-1793 is a potent antitumor agent that inhibits tumor growth via the regulation of HIF-1, and demonstrates significant therapeutic potential for solid cancers.