Publications (2)9 Total impact
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ABSTRACT: A functional drug carrier comprised of folic acid modified lipid-shell and polymer-core nanoparticles (FLPNPs) including poly(D,L-lactide-co-glycolide) (PLGA) core, PEGylated octadecyl-quaternized lysine modified chitosan (PEG-OQLCS) as lipid-shell, folic acid as targeting ligand and cholesterol was prepared and evaluated for targeted delivery of paclitaxel (PTX). Confocal microscopy analysis confirmed the coating of the lipid-shell on the polymer-core. Physicochemical characterizations of FLPNPs, such as particle size, zeta potential, morphology, encapsulation efficiency, and in vitro PTX release, were also evaluated. The internalization efficiency and targeting ability of FLPNPs were demonstrated by flow cytometry and confocal microscopy. PTX loaded FLPNPs showed a significantly higher cytotoxicity than the commercial PTX formulation (Taxol®). The intravenous administration of PTX encapsulated FLPNPs led to tumor regression and improvement of animal survival in a murine model, compared with that observed with Taxol® and biodistribution study showed that PTX concentration in tumor for PTX encapsulated FLPNPs was higher than other PTX formulations. Our data indicate that PTX loaded FLPNPs are a promising nano-sized drug formulation for cancer therapy.
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ABSTRACT: Since the processes of normal embryogenesis and neoplasia share many of similar pathways, tumor development has been interpreted as an abnormal form of organogenesis. NANOG is a homeodomain-containing transcription factor that functions to maintain self-renewal and proliferation of embryonic stem cells (ESCs). Aberrant expression of NANOG has been observed in many types of human malignancies. However, its potential implication in tumorigenesis has not been fully clarified. In this study, we have employed small interference RNA (RNAi) technology to silence endogenous NANOG expression in breast cancer cells and successfully selected three independent clones with stably inhibited NANOG expression of MCF-7 cells. Functional analysis revealed that down-regulation of NANOG reduced cell proliferation, colony formation and migration ability of MCF-7 cells. Consistently, proliferation of breast cancer MDA-MB-231 cells was also significantly inhibited after the knockdown of NANOG expression. Interestingly, we found that the expression levels of cyclinD1 and c-myc were markedly down-regulated and the cell cycle were blocked at the G0/G1 phases after the knockdown of NANOG, while the expression of cyclinE and signal transducers and activators of transcription3 (STAT3) remained unaffected. In addition, the expression of NANOG and cyclinD1 can be rescued after the transfection of pcDNA3.1 (-)-NANOG expression vector into the three clones. Finally, our chromatin immunoprecipitation (ChIP) experiment showed that NANOG protein can bind to the promoter region of cyclinD1 and regulate cells cycle. Taken together, our findings may not only establish a molecular basis for the role of NANOG in modulating cell cycle progression of breast cancer cells but also suggest a potential target for the treatment of at least some subtypes of breast cancer.
Tianjin Medical University Cancer Institute and HospitalT’ien-ching-shih, Tianjin Shi, China