title: Design, synthesis, and evaluation of chitosan conjugated GGRGDSK peptides as a cancer cell-targeting molecular transporter.
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.
authors.affiliation: Cellulose and Paper Department, National Research Center, Dokki 12622, Cairo, Egypt; Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, United States.
authors.forename: Naglaa S
authors.initials: NS
authors.lastname: El-Sayed
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, United States.
authors.forename: Amir N
authors.initials: AN
authors.lastname: Shirazi
authors.affiliation: Cellulose and Paper Department, National Research Center, Dokki 12622, Cairo, Egypt.
authors.forename: Magda G
authors.initials: MG
authors.lastname: El-Meligy
authors.affiliation: Chemistry Department, Faculty of Science, Ain Shams University, Abbassia, Cairo 11566, Egypt.
authors.forename: Ahmed K
authors.initials: AK
authors.lastname: El-Ziaty
authors.affiliation: Cellulose and Paper Department, National Research Center, Dokki 12622, Cairo, Egypt.
authors.forename: Zenat A
authors.initials: ZA
authors.lastname: Nagieb
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, United States.
authors.forename: Keykavous
authors.initials: K
authors.lastname: Parang
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, United States. Electronic address: tiwari@chapman.edu.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Tiwari
mesh_terms: D000595:Amino Acid Sequence; D001692:Biological Transport; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D048271:Chitosan / Q000737:chemistry*; D004396:Coloring Agents / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D015195:Drug Design; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D016023:Integrins / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D010539:Permeability; D010748:Phosphopeptides / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D004396:Coloring Agents; D004337:Drug Carriers; D016023:Integrins; D009842:Oligopeptides; D010748:Phosphopeptides; D014867:Water; C047981:arginyl-glycyl-aspartic acid; D048271:Chitosan
keywords: Cancer cell lines; Chitosan oligosaccharide; GGRGDSK peptide; Ionic gelation; Phosphopeptide; Sulfo-SMCC linker