Harnessing the power of -CD-functionalized star-PLA for Doxorubicin delivery in Osteosarcoma cells

Star polymers are biomaterials of growing interest in the biomedical field as powerful injectable drug delivery systems. Their exclusive structure, consisting of multiple variable-length linear chains (arms) radiating from a central core, is responsible for remarkable properties unattainable by linear polymers. [1,2] In the framework of our studies dealing with the design of novel polymer-based Nanotherapeutics [3-5], we recently synthetized a novel three-armed star polylactic acid functionalized with -CD (star PLA-CD) exploiting a proper combination of Ring-Opening Polymerization (ROP) of L-lactide using glycerol as the initiator, Steglish esterification and copper catalyzed 1,3-dipolar Huisgen cycloaddition (CuAAC). The azide-alkyne Huisgen click reaction afforded in good yield and without side products a novel amphiphilic three-armed star PLA-CD copolymer able to self-assemble in water into nanoparticles and to incorporate the antitumoral drug Doxorubicin (Dox). A sustained and prolonged drug release was promoted from star PLA-CD@Dox by acidic pH that stimulated nanoparticles disassembly together with DOX protonation. In vitro biological studies on a panel of osteosarcoma cells (U2, MG63, Saos-2, MNNG-HOS-GFP, 143B) pointed out the ability of our star PLA-CD@Dox nanocarriers to effectively inhibit tumoral cells proliferation, without toxicity on bone marrow derived mesenchymal stem cells (BM-MSCs), used as healthy control.