期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 87, 期 -, 页码 611-622出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijbiomac.2016.03.020
关键词
Chitosan oligosaccharide; GGRGDSK peptide; Sulfo-SMCC linker; Phosphopeptide; Ionic gelation; Cancer cell lines
资金
- Egyptian Cultural Affairs and Mission Sector, Ministry of Higher Education, Egypt
- Chapman University School of Pharmacy
Targeting cancer cells using integrin receptor is one of the promising targeting strategies in drug delivery. In this study, we conjugated an integrin-binding ligand (GGRGDSK) peptide to chitosan oligosaccharide (COS) using sulfo-SMCC as a bifunctional linker to afford COS-SMCC-GGRGDSK. The conjugated polymer was characterized by FT-IR,H-1 NMR, C-13 NMR, and SEM. COS-SMCC-GGRGDSK did not show cytotoxicity up to a concentration of 1 mg/mL in the human leukemia cell line (CCRF-CEM). The conjugate was evaluated for its ability to enhance the cellular uptake of a cell-impermeable cargo (e.g., F'-G(pY)EEI phosphopeptide) in CCRF-CEM, and human ovarian carcinoma (SK-OV-3) cancer cell lines. Additionally, RGD modified and unmodified COS polymers were used to prepare nanoparticles by ionic gelation and showed particle size ranging from 187 to 338 nm, and zeta potential of 12.2-18.3 mV using dynamic light scattering. The efficiency of COS-NPs and COS-SMCC-RGDSK NPs was assayed for translocation of two synthetic cytotoxic agents ((2-(2-aminoethylamino)-4-(4-chloropheny1)-6-(1H-indo1-3-yl) nicotinonitrile (ACIN), and 2-(2-aminoethylamino)-6-(1H-indol-3-yl)-4-(4-methoxyphenyl)-nicotinonitrile (AMIN)) into CCRFCEM and human prostate (DU-145) cancer cell lines. The results showed a dramatic reduction in the cell viability on their treatment with RGD targeted COS NPs in comparison to paclitaxel (PTX), free drug, and drug-loaded COS NPs. (C) 2016 Elsevier B.V. All rights reserved.
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