Tóm tắt

We report the synthesis, characterization and biological profile of new bis-triazoled cyclopolylactides (c-PLA,c-PLA-FA,c-PLA-Rhod) obtained by an optimized combination of ROP and clickchemistry reactions.Cyclo-PLArnhaving a number average molecular weight of 6000 gmolrn−1rnand a polydispersity index of 1.52 was synthetizedrnbyclickring-closure of well-definedα,ω-heterodifunctional linear precursors, followed by quaternarization ofrnN3-triazole nodes, and subsequent CuAAC with azido-folate and azido-rhodamine yielding jellyfish-shaped c-PLA-FA and c-PLA-Rhod. Salinomycin (Sal) was loaded into jellyfish-shaped c-PLA-FA and c-PLA-Rhod nano-particles (NPs) by nanoprecipitation, with a good encapsulation efficiency (79% and 84%, respectively) andrnloading content (7.1% and 7.6%, respectively). The biological studies focused on their antiproliferative effectsrnon osteosarcoma bulk MG63 and cancer stem cells (CSCs). The cycloPLA-based NPs, with a size ranging betweenrn125 and 385 nm, killed CSCs and MG63, with a higher efficacy on CSCs; they (unloaded or Sal-loaded) evoked onrnCSCs a cellular response similar to the payload, with a higher effect than the free Sal. Internalization studiesrnindicated a fast cellular uptake (within 2 h) and sarcospheres remained fluorescent till 72 h. To the best of ourrnknowledge, this is thefirst study reporting anti-CSCs properties of cycloPLA with jellyfish architecture and wernbelieve could contribute to the development of effective strategies for osteosarcoma targeting.