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Study on the Synthesis and Anti-tumor Effect of Plumbagin-Single Walled Carbon Nanotubes Conjugate

Author: ZhongQuanQiang
Tutor: LiMei
School: Guangxi Medical University
Course: Pharmacology
Keywords: Plumbagin Single - walled carbon nanotubes Complexes Drug carrier Apoptosis Bel-7402,
CLC: R285.5
Type: Master's thesis
Year: 2011
Downloads: 57
Quote: 0
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Abstract


Plumbagin (5 - hydroxy-2 - methyl-1 ,4 - naphthoquinone PLB), is extracted from the root of the blue snow Branch plant Plumbago obtained with antiparasitic, antibacterial antifibrotic and anti nature of the oxidation, and other applications in traditional medicine history of over 2,500 years. The in vitro and in vivo experiments indicate that plumbagin has a good anti-tumor activity. Antitumor activity against plumbagin, the research group has carried out a lot of preliminary work, and explore its anti-tumor effect. But plumbagin has poor water solubility and high toxicity, limiting the development and clinical application of its anti-tumor chemotherapy drugs. Single-walled carbon nanotubes (SWNTs) is a single layer of graphite rolled up tubular nanomaterials, water-soluble single-walled carbon nanotubes modified proteins, DNA, small interfering RNA (siRNA) and drug molecules can be delivered to the tumor cells . Objective: 1. Prepared by polyethylene glycol (PEG)-modified single-walled carbon nanotubes with plumbagin the coupling effect the PLB-PEG-SWNTs complex, improve plumbagin water-soluble. 2 expedition the PLB-PEG-SWNTs's in vitro anti-tumor effect. Method: 1. Use of strong acid oxidation and shear the SWNTs, and then be covalently modified by PEG PEG-SWNTs-last the PLB chemosynthesis through covalent coupling with the PEG-SWNTs. By Fourier transform infrared spectroscopy (FT-IR) and transmission electron microscopy (TEM) prepared PLB-PEG-SWNTs complex composition and structure characterization, with UV - visible spectrophotometry (UV-Vis) Determination of PLB -PEG-SWNTs plumbagin loading. 3. Research The PLB-PEG-SWNTs composite objects of Bel-7402 CNE1, HepG-2 and MCF-7 tumor cell lines affect the MTT assay. 4. Use of the TEM observation tumors cell ultrastructure, application of acridine orange fluorescent staining and flow cytometry method to study the impact of PLB-PEG-SWNTs Bel-7402 cell apoptosis and cell cycle. Results: 1. Preparation obtained PLB-PEG-SWNTs having a good water solubility. 2.TEM characterization showed that the size distribution through the length of the SWNTs in the oxidation after shearing of 100 at 500 nm; FT-IR spectrum shows, PLB, and SWNTs via an ester bond coupling. 3. PLB-PEG-SWNTs Bel-7402, CNE1, HepG-2 and MCF-7 tumor cell growth were significantly inhibited, and dose-dependent manner. , PLB-PEG-SWNTs 80μg/mL IC50 value of Bel-7402 (equivalent containing free Plumbago prime 1.12μg/mL) 1.12μg/mL significantly higher lower than the IC50 values ??plumbagin 7μg/mL free. PLB-PEG-SWNTs dose group (50,150,450 μg / mL) affect the performance of Bel-7402 cell cycle G2 / M phase, administration after 24h, the apoptosis index were 2.20 ± 0.03%, 3.26 ± 0.67 %, 24.33 ± 1.70%, the control group, the apoptotic index was 0.383 ± 0.097%. Acridine orange fluorescence staining cells showed obvious morphological changes of apoptosis. Electron microscope showed that the the PLB-PEG-SWNTs after administration of Bel-7402 cell nuclear chromatin condensation and marginalization, nuclear fragmentation, cytoplasmic vacuolization obvious. Conclusion: PEG-SWNTs PLB coupling can be prepared to get a good water-soluble compound drugs. 2. PLB-PEG-SWNTs has significant anti-tumor effects in vitro. 3. PLB-PEG-SWNTs block cells at the G2 / M phase, inducing tumor cell apoptosis.

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