title: RAFT-derived polymer-drug conjugates: poly(hydroxypropyl methacrylamide) (HPMA)-7-ethyl-10-hydroxycamptothecin (SN-38) conjugates.
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. 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.
authors.affiliation: CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Charlotte C
authors.initials: CC
authors.lastname: Williams
authors.forename: San H
authors.initials: SH
authors.lastname: Thang
authors.forename: Tina
authors.initials: T
authors.lastname: Hantke
authors.forename: Uwe
authors.initials: U
authors.lastname: Vogel
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeberger
authors.forename: John
authors.initials: J
authors.lastname: Tsanaktsidis
authors.forename: Bernd
authors.initials: B
authors.lastname: Lepenies
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D000077146:Irinotecan; D051379:Mice; D011108:Polymers / Q000737:chemistry*; D012995:Solubility
chemical_list: D000178:Acrylamides; D000970:Antineoplastic Agents; D011108:Polymers; D000077146:Irinotecan; C032976:N-(2-hydroxypropyl)methacrylamide; D002166:Camptothecin