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

Christopher D. Hein, Xin Ming Liu, Fu Chen, Diane M. Cullen, Dong Wang

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.A novel bone-targeting delivery system is described that uses a multiblock α-cyclodextrin/poly(ethylene glycol) polyrotaxane scaffold. The system is assembled by conjugating the bone-targeting moiety, alendronate (ALN), to α-cyclodextrin (α-CD), threading these conjugates onto an acetylene-terminated PEG backbone, and copolymerizing the entire assembly with a sterically bulky diazide monomer. The overall bone-binding affinity can be freely adjusted.

Original languageEnglish (US)
Pages (from-to)1544-1556
Number of pages13
JournalMacromolecular Bioscience
Volume10
Issue number12
DOIs
StatePublished - Dec 13 2010

Fingerprint

Alendronate
Cycloaddition
Cycloaddition Reaction
Copper
Bone
Polyethylene glycols
Cyclodextrins
Bone and Bones
Ethylene Glycol
Monomers
Click Chemistry
Acetylene
Scaffolds
Polymers
polyrotaxane
Imaging techniques

Keywords

  • Bisphosphonates
  • Bone-targeting
  • Click chemistry
  • Drug delivery systems
  • Polyrotaxanes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

The Synthesis of a Multiblock Osteotropic Polyrotaxane by Copper(I)-Catalyzed Huisgen 1,3-Dipolar Cycloaddition. / Hein, Christopher D.; Liu, Xin Ming; Chen, Fu; Cullen, Diane M.; Wang, Dong.

In: Macromolecular Bioscience, Vol. 10, No. 12, 13.12.2010, p. 1544-1556.

Research output: Contribution to journalArticle

Hein, Christopher D. ; Liu, Xin Ming ; Chen, Fu ; Cullen, Diane M. ; Wang, Dong. / The Synthesis of a Multiblock Osteotropic Polyrotaxane by Copper(I)-Catalyzed Huisgen 1,3-Dipolar Cycloaddition. In: Macromolecular Bioscience. 2010 ; Vol. 10, No. 12. pp. 1544-1556.
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