Cytocompatible Triblock Copolymers with Controlled Microstructure Enabling Orthogonally Functionalized Bio-polymer Conjugates

α,ω-Functionalized block copolymers create various opportunities across myriads of applications such as linkers for targeted drug delivery systems. Combining them with the exceptional properties of polyvinyl phosphonates, such as high control over polymer architecture and biocompatibility, further reinforces their benefits. This study focuses on synthesizing the α-allyl-ω-TMSpropargyl-block-co-polymer P(DAlVP-DEVP-DPrTMSVP) by rare-earth metal-mediated group transfer polymerization. The monomers involved in this process are functionalized diallyl vinyl phosphonate (DAlVP) and dipropargyl vinyl phosphonate (DPrTMSVP), as well as hydrophilic diethyl vinyl phosphonate (DEVP), enabling the incorporation of diverse functionalities into the polymer structure. Click chemistry, including azide-alkyne cycloaddition (AAC) and thiol-ene reactions, facilitates specific and controlled modifications of polymer side chains. Various model substrates, such as benzyl azide, 3-azido-7-hydroxycoumarin, and cysteamine, show the scope of these modifications. The potential in (bio)medical applications is proven with the polymer-biomolecule conjugate α-cholesteryl-ω-folate-block-co-polyvinyl phosphonate, exhibiting remarkable biocompatibility. Our versatile approach also establishes a synthetic platform for drug delivery systems, for instance, in targeted therapy.