Among the numerous classes of drug delivery systems, drug-loaded polymer nanoparticles have attracted much attention. Although this approach has led to numerous encouraging results and proofs of concept in vitro, important limitations still remain, which may explain the lower number of successful in vivo studies and the limited number of marketed nanomedicines.
In this view, the current project aims at developing an innovative and versatile nanoparticulate platform to prepare well-defined amphiphilic polymer-drug “prodrug” nanoassemblies by means of controlled/living radical polymerization (CLRP) techniques, such as nitroxide-mediated polymerization (NMP), atom transfer radical polymerization (ATRP), or reversible addition-fragmentation chain transfer (RAFT). The new, facile and general strategy we propose relies on the controlled growth of biorelevant polymers (hydrophobic or hydrophilic) from functionalized drugs of the opposite solubility under CLRP conditions. This will result in well-defined amphiphilic species, bearing one drug molecule at the extremity of each polymer chain, able to self-assemble into nanoassemblies of various morphologies, exhibiting high drug payloads and thus high biological activities. This new methodology tends to be: (i) universal as it is virtually applicable to multiple drugs and consequently to multiple pathologies and (ii) versatile as various polymer prodrugs can be produced with high degree of control and flexibility over their structures (e.g., nature of the drug/polymer couple, nature of the linker, polymer chain length, etc.).
This will be illustrated by the synthesis of a broad range of polymer prodrugs from a wide selection of drugs having demonstrated activities against cancer. Comprehensive characterization of the resulting nanoassemblies will be performed as well as their pharmacological evaluation in vitro (cell culture) and in vivo on relevant models, according to standardized protocols.
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