Les publications de l’UMR
Despite the huge efforts made in the last half century to develop new controlled polymer- ization techniques, synthetic polymers are without exception composed of macro- molecules with a molecular weight distribution. Several studies dealt with relationship between polymer molecular weight, structure or architecture and properties, but only recently, researchers are trying to develop tools for creating fully monodisperse macro- molecules or even sequence-defined ones. Dispersity was shown to lead to a misinterpre- tation of the data as highlighted by recent studies. In the present paper, the synthesis of poly(ethylene imine)s derivatives (PEId) with well-defined structure, precisely controlled molecular weight and subsequent PEGylation is reported. The strategy can be further used in order to prepare long polymer chain with not only controlled molecular weight but also different monomer sequences.
Polydiacetylenic nanofibers (PDA-Nfs) obtained by photo- polymerization of surfactant 1 were optimized for intracellular delivery of small interfering RNAs (siRNAs). PDA-Nfs/siRNA com- plexes efficiently silenced the oncogene Lim-1 in the renal cancer cells 786-O in vitro. Intraperitoneal injection of PDA-Nfs/siLim1 downregulated Lim-1 in subcutaneous tumor xenografts obtained with 786-O cells in nude mice. Thus, PDA-Nfs represent an innova- tive system for in vivo delivery of siRNAs.
Recently, it has been shown that the efficiency of antitumoral drugs can be enhanced when combined with therapeutic siRNAs. In the present study, an original platform based on polydiacetylenic micelles containing a cationic head group able to efficiently deliver a small interfering RNA (siRNA) targeting the PLK-1 gene while offering a hydrophobic environment for encapsulation of lipophilic drugs such as camptothecin is developed. We demonstrate that the co-delivery of these two agents with our micellar system results in a synergistic tumor cell killing of cervical and breast cancer cell lines in vitro. The combined drugs are active in a subcutaneous in vivo cancer model. Altogether, the results show that our nanometric micellar delivery system can be used for the development of new drug–siRNA combo-therapies.
Publication en 2017
Publications in 2017