Construction of I-RGDyC-PEG-PAMAM-DTX targeted drug delivery system and study of its physicochemical properties and biological activity.

Objective: To construct a novel targeted drug delivery nanoprobe: iodine-131-arginine-glycine-aspartate-tyrosine-cysteine peptide-polyethylene glycol-fifth generation polyamide-amine-docetaxel (I-RGDyC-PEG-PAMAM-DTX) and to investigate its physicochemical properties and biological activity.

Materials And Methods: Docetaxel was wrapped by solvent volatilization method, and the regression curve of DTX was constructed by high-performance liquid chromatography to determine its drug loading. The particle size of RGDyC-PEG-PAMAM-DTX was detected by dynamic light scattering. The I labeling was performed by a chloramine-T method and purified by Sephadex-G50 column chromatography, and it is in vitro stability and lipid-water partition coefficient was investigated. The cytotoxicity of RGDyC-PEG-PAMAM-DTX and I-RGDyC-PEG-PAMAM-DTX on A549 cells in vitro was detected by Cell Counting Kit-8 assay.

Results: Arginine-glycine-aspartate-tyrosine-cysteine peptide-PEG-PAMAM-DTX was successfully prepared by solvent volatilization with a loading capacity of about 44μg/mg. The average particle size of RGDyC-PEG-PAMAM-DTX was 57.8nm; the labeling rate of I-RGDyC-PEG-PAMAM-DTX by the chloramine-T method was 74.09%-76.09%, and the radiochemical purity was 88.9%-92.6% after purification. The in vitro stability showed that the radiochemical purity was above 80% after 72h in fetal bovine serum and PBS buffer (25C and 37C).CCK-8 assay showed that RGDyC-PEG-PAMAM-DTX and I-RGDyC-PEG-PAMAM-DTX had more pronounced cytotoxic effects than free DTX and I.

Conclusion: Iodine-131-RGDyC-PEG-PAMAM-DTX has good physicochemical properties and apparent cytotoxic effectsandis expected to be used in treating tumors.