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Design, synthesis, and evaluation of chitosan conjugated GGRGDSK peptides as a cancer cell-targeting molecular transporter.
- Source :
-
International journal of biological macromolecules [Int J Biol Macromol] 2016 Jun; Vol. 87, pp. 611-22. Date of Electronic Publication: 2016 Mar 11. - Publication Year :
- 2016
-
Abstract
- 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, (1)H NMR, (13)C NMR, and SEM. COS-SMCC-GGRGDSK did not show cytotoxicity up to a concentration of 1mg/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 338nm, and zeta potential of 12.2-18.3mV 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-chlorophenyl)-6-(1H-indol-3-yl) nicotinonitrile (ACIN), and 2-(2-aminoethylamino)-6-(1H-indol-3-yl)-4-(4-methoxyphenyl)-nicotinonitrile (AMIN)) into CCRF-CEM 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.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Biological Transport
Cell Line, Tumor
Chemistry Techniques, Synthetic
Coloring Agents chemistry
Coloring Agents metabolism
Drug Carriers toxicity
Humans
Hydrophobic and Hydrophilic Interactions
Integrins metabolism
Nanoparticles chemistry
Oligopeptides toxicity
Particle Size
Permeability
Phosphopeptides chemistry
Phosphopeptides metabolism
Solubility
Water chemistry
Chitosan chemistry
Drug Carriers chemistry
Drug Design
Oligopeptides chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0003
- Volume :
- 87
- Database :
- MEDLINE
- Journal :
- International journal of biological macromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 26976071
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2016.03.020