The Synthesis of a Multiblock Osteotropic Polyrotaxane by Copper(I)‐Catalyzed Huisgen 1,3‐Dipolar Cycloaddition

Abstract The design and synthesis of a novel bone‐targeting polyrotaxane delivery system that utilizes alendronate (ALN) as targeting moiety is presented in this manuscript. For the introduction of ALN, it is first conjugated to α‐cyclodextrin (α‐CD) and subsequently threaded onto a short poly(ethylene glycol) (PEG) chain, forming a pseudopolyrotaxane. Using click chemistry, this assembly is copolymerized with bulky monomers that bear imaging and/or therapeutic agent(s) to prevent ALN‐functionalized α‐CD from dethreading. Overall bone affinity of this novel polymer conjugate can be easily controlled by changing the number of ALN‐α‐CD incorporated. The osteotropicity of the delivery system was also confirmed in vivo. magnified image