Browsing by Author "Hsieh, Ming-Fa"

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Doxorubicin-Loaded Nanosized Micelles of a Star-Shaped Poly(epsilon-Caprolactone)-Polyphosphoester Block Co-polymer for Treatment of Human Breast Cancer
(2011)
Nguyen-Van Cuong
;
Hsieh, Ming-Fa
;
Chen, Yung-Tsung
;
Liau, Ian
;
應用化學系
Star-shaped co-polymers based on the backbone of poly(epsilon-caprolactone) were synthesized by a ring-opening reaction using pentaerythritol as initiator and Sn(Oct)(2) as catalyst. The star-shaped poly(epsilon-caprolactone) polymer was then chain extended with a terminal block of poly(ethyl ethylene phosphate) to form a copolymer, poly(epsilon-caprolactone)-poly(ethyl ethylene phosphate), when using the cyclic ethyl ethylene phosphate monomer. The amphiphilic block co-polymers can self-assemble into nanoscopic micelles with a mean diameter of 150 nm and a spherical shape. Additionally, the prepared micelles did not induce hemolysis and nitric oxide production in vitro based on nitric oxide, hemolytic tests and MTT assays. The hydrophobic micellar cores encapsulated doxorubicin (DOX) in an aqueous solution with a loading efficiency of 55.2%. The in vitro release of DOX from DOX-loaded micelles was pH dependent. DOX-loaded micelles present significantly enhanced cytotoxicity to both MCF-7/drug-sensitive and MCF-7/drug-resistant cells after second incubation. Moreover, results of confocal microscopy and flow cytometry of DOX-loaded micelles demonstrate the feasibility of this delivery system for effective therapy of drug-resistant tumours. (C) Koninklijke Brill NV, Leiden, 2011
Overcoming Multidrug Resistance of Breast Cancer Cells by the Micellar Doxorubicin Nanoparticles of mPEG-PCL-Graft-Cellulose
(2011-01-01)
Chen, Chao-Hsuan
;
Cuong, Nguyen-Van
;
Chen, Yung-Tsung
;
So, Regina Cheng
;
Liau, Ian
The amphiphilic block copolymer methoxy-poly(ethylene glycol)-poly(epsilon-caprolactone) (mPEG-PCL) was grafted to 2-hydroxyethyl cellulose (HEC) to produce nano-sized micellar nanoparticles. The nanoparticles were loaded with anti-tumor drug, doxorubicin (DOX) and the size of the DOX-loaded nanoparticles were determined by dynamic light scattering (DLS) in aqueous solution to be from 197.4 to 230 nm. The nanoparticles subjected to co-culture with macrophage cells showed that these nanoparticles used as drug carrier are not recognized as foreign bodies. Overexpression of P-glycoprotein (P-gp) is an important factor in the development of multidrug resistance (MDR) in many cancer cells. In this study, Western blot and Rhodamine 123 were used to monitor the relative P-glycoprotein expression in human breast cancer cell lines MCF-7/WT and MCF-7/ADR. The endocytosis of the DOX-loaded nanoparticles by breast cancer cells is more efficient observed under a confocal laser scanning microscopy (CLSM) and a flow cytometry in MCF7/ADR cells, compared to the diffusion of the free drug into the cytoplasm of cells. Based on these findings, we concluded that the nanoparticles made from mPEG-PCL-g-cellulose were effective in overcoming P-gp efflux in MDR breast cancer cells.
Overcoming Multidrug Resistance of Breast Cancer Cells by the Micellar Drug Carriers of mPEG-PCL-graft-cellulose
(2009)
Chen, Yung-Tsung
;
Chen, Chao-Hsuan
;
Hsieh, Ming-Fa
;
Chan, Ann Shireen
;
Liau, Ian
The amphiphilic block copolymers methoxypoly (ethylene glycol)-poly (epsilon-caprolactone) (mPEG-PCL) was grafted to 2-hydroxyethyl cellulose (HEC) to produce water-soluble copolymers. Doxorubicin (DOX)-loaded nanoparticles were prepared by dialysis method and the sizes of nanoparticles were determined by dynamic light scattering (DLS) in solution. The size of the nanoparticles was in the range of 197.4 to 340.7 nm. Rhodamine 123 was used to probe the relative P-glycoprotein (P-gp) expression in human breast cancer cell lines MCF-7/WT and MCF-7/ADR. Confocal laser scanning microscopy (CLSM) showed a difference between the fluorescence images of DOX-loaded micelles and free DOX. For a quantitative basis, flow cytometry was done on both cell lines treated with DOX-loaded micelles and free DOX to compare a difference in effect. The amount of DOX-loaded micelles in MCF-7/ADR increased compared to that in the MCF-7/WT cells. This gives insight into how the micellar system developed in this study overcomes the multidrug resistance (MDR) effect.
Synthesis and Characterization of PEG-PCL-PEG Triblock Copolymers as Carriers of Doxorubicin for the Treatment of Breast Cancer
(2010-09-15)
Cuong, Nguyen-Van
;
Hsieh, Ming-Fa
;
Chen, Yung-Tsung
;
Liau, Ian
;
應用化學系分子科學碩博班
Triblock copolymers of monomethoxy poly(ethylene glycol) (mPEG) and epsilon-caprolactone (CL) were prepared with varying lengths of poly(E-caprolactone) (PCL) compositions and a fixed length of mPEG segment. The molecular characteristics of triblock copolymers were characterized by NMR, gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). These amphiphilic linear copolymers based on PCL hydrophobic chain and hydrophilic mPEG ending, which can self-assemble into nanoscopic micelles with their hydrophobic cores, encapsulated doxorubicin (DOX) in an aqueous solution. The particle size of prepared micelles was around 40-92 nm. The DOX loading content and DOX loading efficiency were from 3.7-7.4% to 26-49%, respectively. DOX-released profile was pH-dependent and faster at pH 5.4 than pH 7.4. Additionally, the cytotoxicity of DOX-loaded micelles was found to be similar with free DOX in drug-resistant cells (MCF-7/adr). The great amounts of DOX and fast uptake accumulated into the MCF-7/adr cells from DOX-loaded micelles suggest a potential application in cancer chemotherapy. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 117: 3694-3703, 2010