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) (PEG42-b-PMLABe), the biotin-poly(ethylene glycol)-bpoly( benzyl malate) (Biot-PEG62-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, PEG42-PMLABe or Biot-PEG62-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, PEG42-PMLABe or Biot-PEG62-PMLABe nanoparticles showed an in vitro cytotoxicity similar to that of free Dox. Moreover, the DiD oil loaded Biot-PEG62-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.

International audienceThe "immortal" coordination-insertion ring-opening polymerization of benzyl malolactonate (MLABe) initiated by the two-component catalyst system based on the zinc amide precursor, (BDI)Zn[N(SiMe3)2] (BDI = β-diiminate ligand), and benzyl alcohol (BnOH) acting as a co-initiator and a chain transfer agent proceeds in bulk at 40 °C. Functional telechelic poly(β-benzyl malolactonate)s, H-PMLABe-OBn, are thus obtained. Sequential copolymerization with trimethylene carbonate (TMC) affords block copolymers, PTMC-b-PMLABe, which are alternatively prepared from the chemical coupling of the PMLABe-COOH and PTMC-OH homopolymers. Simultaneous copolymerization of both the lactone and the carbonate monomers offers the PTMC-co-PMLABe random copolymers. The (co)polymers have been characterized by NMR, FT-IR, SEC and DSC analyses. These represent the first examples of β-benzyl malolactonate/carbonate copolymers. More importantly, these (co)polymers could be synthesized free of metallic residues thereby making them suitable as biomedical and pharmaceutical biomaterials