title: Cell-penetrable lysine dendrimers for anti-cancer drug delivery: synthesis and preliminary biological evaluation.
abstract: Improving the cell penetration and enhancing the cell selectivity of drugs have been approved for overcoming the major drawbacks of chemotherapeutic agents: the toxicity to normal cells and the drug resistance in tumors. In this paper, lysine dendrimers (G1-G3) were chosen as novel cell-penetrating carriers for anti-cancer drugs based on the internalization mechanism of cell-penetrating peptides and the characteristics of dendritic peptides. After labeling with fluorescein isothiocyanate (FITC), the cell-penetrable capacity of lysine dendrimers was certified by flow cytometric analysis. In a preliminary biological evaluation, the conjugates of lysine dendrimers and 5-fluorouracil showed the expected advantages: stable drug release, low toxicity to normal cells, and moderate inhibition of tumor cells. These results imply that cell-penetrable lysine dendrimers could be potential carriers in drug delivery of anti-cancer medicine.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System of Education Ministry, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Fu
authors.forename: Wen
authors.initials: W
authors.lastname: Ren
authors.forename: Lifang
authors.initials: L
authors.lastname: Ma
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D065546:Drug Liberation; D005434:Flow Cytometry; D005472:Fluorouracil / Q000008:administration & dosage*; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008239:Lysine / Q000737:chemistry*; D015394:Molecular Structure; D011355:Prodrugs / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; D050091:Dendrimers; D004337:Drug Carriers; D011355:Prodrugs; D008239:Lysine; D005472:Fluorouracil
keywords: 5-Fluorouracil; Cell-penetrating; Cellular selectivity; Drug delivery; Lysine dendrimers