title: Formulation of temozolomide-loaded nanoparticles and their targeting potential to melanoma cells.
abstract: The present study was carried out to prepare and evaluate a temozolomide (TMZ)-loaded polyamide-amine dendrimer (PAMAM)‑based nanodrug delivery system, and to explore its ability to target human melanoma (A375) cells in vitro. Firstly, PAMAM-PEG and PAMAM-PEG-GE11 were synthesized by substitution and addition reactions, and their products were identified and characterized by fourier transform-infrared (FTIR), proton nuclear magnetic resonance (1H-NMR) and transmission electron microscopy (TEM), as well as differential light scattering (DLS). Using fluorescein isothiocyanate (FITC)-modified PAMAM, we synthesized FITC-PAMAM, FITC-PAMAM-PEG and FITC-PAMAM-PEG-GE11. Fluorescence microscopy and flow cytometry were used to monitor the uptake of A375 cells of these three nanomaterials. Secondly, TMZ-PAMAM‑PEG‑GE11-HA drug complexes were prepared by ultrasonic emulsification, and their particle size, zeta potential and morphology were evaluated by DLS and TEM. Drug loading (DL) and encapsulation efficiency (EE) were assayed by ultraviolet spectrophotometry. Thirdly, we ascertained whether TMZ-PAMAM-PEG-GE11-HA conjugates could target A375 cells in vitro. The TMZ-PAMAM‑PEG‑GE11-HA nanodrug delivery system was successfully synthesized according to FTIR and 1H-NMR. Its mean particle size was 183.2 nm and zeta potential was -0.01 mV. It was a regular sphere with good uniformity. The EE of TMZ-PAMAM-PEG-GE11-HA was ~50.63% and DL ~10.4%. TMZ-PAMAM-PEG-GE11-HA targeted A375 cells in vitro. In conclusion, the TMZ-PAMAM‑PEG-GE11-HA nanodrug delivery system was successfully prepared, and demonstrated its potential for targeting A375 cells in vitro. This system enhanced the sensitivity of A375 cells to TMZ, and provided a novel targeted strategy for the treatment of metastatic melanoma.
authors.affiliation: Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Guan
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Jianqin
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Dermatology, Affiliated Huai'an Hospital of Xuzhou Medical College, Huaian, Jiangsu 223002, P.R. China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Radiotherapy, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Radiotherapy, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Yanqun
authors.initials: Y
authors.lastname: Liu
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D050091:Dendrimers; C572557:GE11 peptide; C104700:PAMAM Starburst; D010455:Peptides; D003606:Dacarbazine; D016650:Fluorescein-5-isothiocyanate; D000077204:Temozolomide