RAFT-Derived Polymer-Drug Conjugates: Poly(hydroxypropyl methacrylamide) (HPMA)-7-Ethyl-10-hydroxycamptothecin (SN-38) Conjugates

Charlotte Claire Williams, San H. Thang, Tina Hantke, Uwe Vogel, Peter H. Seeberger, John Tsanaktsidis, Bernd Lepenies

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25 Citations (Scopus)

Abstract

A series of well-defined polymer-drug conjugates were prepared in order to modify the physical properties of a known cytotoxic drug, 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan (CPT-11). Reversible addition-fragmentation chain transfer (RAFT) polymerisation was used to covalently and site-specifically append a defined N-(2-hydroxypropyl)methacrylamide (HPMA) polymer to SN-38 using a graft-from process. These poly-HPMA-SN-38 conjugates displayed excellent aqueous solubility and stability, whilst retaining the cytotoxic activity of the parent SN-38. Invitro co-culture assays containing both cancer and noncancer cell lines demonstrated the specificity of RAFT-derived poly-HPMA-SN-38 conjugates for cancerous cells. The concept of post-optimisation modification of small-molecule drugs through a graft-from polymer conjugation method is introduced.

Original languageEnglish
Pages (from-to)281-291
Number of pages11
JournalChemMedChem
Volume7
Issue number2
DOIs
Publication statusPublished - 6 Feb 2012
Externally publishedYes

Keywords

  • Camptothecins
  • Drug delivery
  • Polymer-drug conjugates
  • Polymers
  • RAFT polymerization

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