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RAFT‐Derived Polymer–Drug Conjugates: Poly(hydroxypropyl methacrylamide) (HPMA)–7‐Ethyl‐10‐hydroxycamptothecin (SN‐38) Conjugates
Author(s) -
Williams Charlotte C.,
Thang San H.,
Hantke Tina,
Vogel Uwe,
Seeberger Peter H.,
Tsanaktsidis John,
Lepenies Bernd
Publication year - 2012
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201100456
Subject(s) - conjugate , methacrylamide , raft , chemistry , drug , polymer , combinatorial chemistry , pharmacology , copolymer , organic chemistry , medicine , acrylamide , mathematical analysis , mathematics
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. In vitro 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.