Click Synthesis And Properties Of Multi-armed And Hyperbranched Polylysine Copolymers

Polypeptides and their copolymers have been widely used for drugdelivery and nanomedicine. The polymer topology and composition are thedeterming parameters of physicochemical and drug release properties.However, the studies on hyperbranched and star shaped polylysine are rare.In this article, hyperbranched poly (-benzyloxycarbonyl-L-lysine)-b-poly(ethylene oxide)(HPlys-b-PEO) and A2B4poly(-benzyloxycarbonyl-L-lysine)-b-poly(ethylene-oxide)(Cys-Plys-b-PEO) were synthesized bycombining photo-click chemistry with ring-opening polymerization, and theirmolecular structure and properties were fully characterized.(1)Synthesis and Characterization of HPlys-b-PEOHyperbranched poly(ε-benzyloxycarbonyl-L-lysine)(HPlys) wassynthesized by click chemistry of an AB2type Plys-macromonomer withα-thiol and ω-alkyne terminal groups (thiol is the A unit, and alkyne is the Bunit), and the resulting HPlys was further conjugated with thiol terminatedpoly(ethylene oxide)(PEO) to generate HPlys-b-PEO block copolymer byconsecutive thiol-yne chemistry. Their molecular structures and physical properties were characterized by FT-IR,1H NMR, DSC, WAXD and POM.HPlys and HPlys-b-PEO mainly assumed an α-helix conformation similar tothe linear precursors, while the liquid-crystal phase transition of Plys segmentdisappeared within HPlys and HPlys-b-PEO. HPlys-b-PEO self-assembledinto nearly spherical micelles in aqueous solution, while it gave a5-foldlower critical aggregation concentration (CAC) than a linear counterpart.Compared with a linear counterpart, HPlys-b-PEO gave a higherdrug-loading capacity and efficiency for the anticancer drug doxorubicin(DOX) and a slower drug-release rate with an improved burst-release profile,enabling them potential use for drug delivery systems.(2)Synthesis and Characterization of A2B4shaped Cys-Plys-b-PEODisulfide-centered star-shaped poly(-benzyloxycarbonyl-L-lysine)-b-poly(ethylene oxide) block copolymers (A2B4type Cys-Plys-b-PEO) weresynthesized by the combination of ring-opening polymerization and thiol-ynechemistry. Their molecular structures and physical properties werecharacterized in detail by FT-IR,1H NMR, gel permeation chromatography,differential scanning calorimetry and wide-angle X-ray diffraction. Despitemainly exhibiting an-helix conformation, the inner Plys blocks withincopolymers greatly prohibited the crystallinity of the outer PEO blocks andpresented a liquid crystal phase transition behavior. These block copolymers Cys-Plys-b-PEO self-assembled into nearly spherical micelles in aqueoussolution, which had a hydrophobic disulfide-centered Plys core surroundedby a hydrophilic PEO corona. As monitored by DLS and TEM, these micelleswere progressively became to smaller micelles of half size under the additionof10mM1,4-dithiothreitol (DTT) at37℃and finally became ones with ahalf size and appreared a dynamic reduction-sensitivity. Despite a gooddrug-loading property, the DOX-loaded micelles of Cys-Plys-b-PEOexhibited a reduction-triggered drug release profile with an improvedburst-release behavior compared with the linear counterpart. Importantly, thiswork provides a versatile strategy for the synthesis of the disulfide-centeredstar-shaped polypeptide block copolymers potentially useful in intracellularglutathione-triggered drug delivery systems.