title: New functional degradable and bio-compatible nanoparticles based on poly(malic acid) derivatives for site-specific anti-cancer drug delivery.
abstract: Design of an efficient site-specific drug delivery system based on degradable functional polymers still remains challenging. In this work, we synthesized and characterized three degradable functional polyesters belonging to the poly(malic acid) family: the poly(benzyl malate) (PMLABe), the poly(ethylene glycol)-b-poly(benzyl malate) (PEG(42)-b-PMLABe), the biotin-poly(ethylene glycol)-b-poly(benzyl malate) (Biot-PEG(62)-PMLABe). Starting from these building blocks, we were able to prepare the corresponding well-defined degradable functional nanoparticles whose toxicity was evaluated in vitro on normal and cancer cell lines. Results have evidenced that the prepared nanoparticles did not show any significant cytotoxicity even at high concentrations. A model anti-cancer drug (doxorubicin, Dox) or a fluorescent probe (1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine, DiD oil) has been encapsulated into PMLABe, PEG(42)-PMLABe or Biot-PEG(62)-PMLABe based nanoparticles in order to evaluate, respectively, the in vitro cytotoxicity of Dox-loaded nanoparticles on normal and cancer cell lines and the ligand (biotin) effect on cellular uptake in vitro using mmt 060562 cell line. Dox-loaded PMLABe, PEG(42)-PMLABe or Biot-PEG(62)-PMLABe nanoparticles showed an in vitro cytotoxicity similar to that of free Dox. Moreover, the DiD oil loaded Biot-PEG(62)-PMLABe based nanoparticles showed a better in vitro cellular uptake than ligand-free DiD oil loaded nanoparticles. Both results evidence the great potential of such degradable functional poly(malic acid) derivatives for the design of highly efficient site-specific anti-cancer nanovectors.
authors.affiliation: UMR 6226 CNRS, Organic and Supramolecular Chemistry, Université de Rennes 1, Ecole Nationale Supérieure de Chimie de Rennes, Avenue du Général Leclerc, CS 50837, F-35708 Rennes Cedex 7, France.
authors.forename: Zhi Wei
authors.initials: ZW
authors.lastname: Huang
authors.forename: Véronique
authors.initials: V
authors.lastname: Laurent
authors.forename: Ghizlane
authors.initials: G
authors.lastname: Chetouani
authors.forename: Julia Y
authors.initials: JY
authors.lastname: Ljubimova
authors.forename: Eggehard
authors.initials: E
authors.lastname: Holler
authors.forename: Thierry
authors.initials: T
authors.lastname: Benvegnu
authors.forename: Pascal
authors.initials: P
authors.lastname: Loyer
authors.forename: Sandrine
authors.initials: S
authors.lastname: Cammas-Marion
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001710:Biotin / Q000737:chemistry; D002232:Carbocyanines / Q000008:administration & dosage / Q000378:metabolism; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D008293:Malates / Q000737:chemistry*; D051379:Mice; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D055672:Static Electricity; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D002232:Carbocyanines; D005456:Fluorescent Dyes; D008293:Malates; D011108:Polymers; C121060:poly(malic acid); D011092:Polyethylene Glycols; C024286:3,3'-dioctadecylindocarbocyanine; D001710:Biotin; D004317:Doxorubicin