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The synthesis of well‐defined propargyl‐functional aliphatic polycarbonates is achieved via the organocatalytic ring‐opening polymerization of prop‐2‐yn‐1‐yl 2‐oxo‐1,3,6‐dioxazocane‐6‐carboxylate (P‐8NC) using a wide variety of commercially available or readily made, shelf‐stable organocatalysts. The resulting homopolymers show low dispersities and end‐group fidelity, with the versatility of the system being demonstrated by the synthesis of telechelic copolymers and block copolymers with molar mass up to 40 kDa. [ABSTRACT FROM AUTHOR]

Hydrophobic and amphiphilic derivatives of the biocompatible and biodegradable poly(dimethylmalic acid) (PdiMeMLA), varying by the nature of the lateral chains and the length of each block, respectively, have been synthesized by anionic ring-opening polymerization (aROP) of the corresponding monomers using an initiator/base system, which allowed for very good control over the (co)polymers' characteristics (molar masses, dispersity, nature of end-chains). Hydrophobic and core-shell nanoparticles (NPs) were then prepared by nanoprecipitation of hydrophobic homopolymers and amphiphilic block copolymers, respectively. Negatively charged NPs, showing hydrodynamic diameters (Dh) between 50 and 130 nm and narrow size distributions (0.08 < PDI < 0.22) depending on the (co)polymers nature, were obtained and characterized by dynamic light scattering (DLS), zetametry, and transmission electron microscopy (TEM). Finally, the cytotoxicity and cellular uptake of the obtained NPs were evaluated in vitro using the hepatoma HepaRG cell line. Our results showed that both cytotoxicity and cellular uptake were influenced by the nature of the (co)polymer constituting the NPs. [ABSTRACT FROM AUTHOR]

[Display omitted] • RGD-NanoStar micellar nanoassemblies loaded with Doxorubicin against osteosarcoma. • Impact of RGD on nanoparticles surface for osteosarcoma chemotherapy. • Dox released from RGD-NanoStar reach the nucleus unlike untargeted NanoStar. • Preserving Doxorubicin from degradation occurring under physiological conditions. • Sustained and prolonged Dox release from RGD-NanoStar@Dox. We developed cyclic RGD-tagged polymeric micellar nanoassemblies for sustained delivery of Doxorubicin (Dox) endowed with significant cytotoxic effect against MG63, SAOS-2, and U2-OS osteosarcoma cells without compromising the viability of healthy osteoblasts (hFOBs). Targeted polymeric micellar nanoassemblies (RGD-NanoStar@Dox) enabled Dox to reach the nucleus of MG63, SAOS-2, and U2-OS cells causing the same cytotoxic effect as free Dox, unlike untargeted micellar nanoassemblies (NanoStar@Dox) which failed to reach the nucleus and resulted ineffective, demonstrating the crucial role of cyclic RGD peptide in driving cellular uptake and accumulation mechanisms in osteosarcoma cells. Micellar nanoassemblies were obtained by nanoformulation of three-armed star PLA-PEG copolymers properly synthetized with and without decoration with the cyclic-RGDyK peptide (Arg-Gly-Asp-D-Tyr-Lys). The optimal RGD-NanoStar@Dox nanoformulation obtained by nanoprecipitation method (8 % drug loading; 35 % encapsulation efficiency) provided a prolonged and sustained drug release with a rate significantly lower than the free drug under the same experimental conditions. Moreover, the nanosystem preserved Dox from the natural degradation occurring under physiological conditions (i.e., dimerization and consequent precipitation) serving as a slow-release "drug reservoir" ensuring an extended biological activity over the time. [ABSTRACT FROM AUTHOR]