title: Synthesis andIn vitroactivity of ROMP-based polymer nanoparticles.
abstract: A new type of polymer nanoparticle (PNP) containing a high density of covalently linked doxorubicin, attached via a non-cleavable amine linkage (amine-linked Dox-PNP) was prepared. Together with a previously reported cleavable carbamate-linked Dox-PNP, this new amine-linked Dox-PNP was subsequently evaluated against free doxorubicin for its cytotoxicity and inhibitory effects on SKNSH wild-type and SKrDOX6 doxorubicin-resistant human neuroblastoma cell lines. Analogous cholesterol-containing PNPs (Chol-PNPs) and indomethacin-containing PNPs (IND-PNPs) were also synthesized and used as the non-cytotoxic controls. While neither cell line was affected by Chol-PNPs or IND-PNPs, SKrDOX6 doxorubicin-resistant cells exhibited similar cytotoxic responses to free doxorubicin and both amine- and carbamate-linked Dox-PNPs, suggesting that doxorubicin or the doxorubicin-containing polymer must be the active agent in the latter case. SKNSH wild-type cells also responded to both Dox-PNPs, albeit at a higher apparent concentration than free doxorubicin alone. The growth of SKNSH wild-type cells was significantly inhibited upon incubation with carbamate-linked Dox-PNPs, as with free doxorubicin, over a 7-day period. In comparison to free doxorubicin, carbamate-linked Dox-PNPs produced a longer (72-h) period of initial inhibition in SKrDOX6 doxorubicin-resistant cells.
authors.affiliation: Department of Chemistry and The International Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208-3113, USA. ; Tel: 847-467-3347.
authors.forename: Deedee
authors.initials: D
authors.lastname: Smith
authors.affiliation: Department of Pediatrics, Children's Memorial Research Center, Cancer Biology and Epigenomics Program, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614, USA.
authors.forename: Sandra H
authors.initials: SH
authors.lastname: Clark
authors.affiliation: Department of Chemistry and The International Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208-3113, USA. ; Tel: 847-467-3347.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Bertin
authors.affiliation: Department of Pediatrics, Children's Memorial Research Center, Cancer Biology and Epigenomics Program, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614, USA ; Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA. ; Tel: 773-755-6341.
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Mirkin
authors.affiliation: Department of Chemistry and The International Institute for Nanotechnology, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208-3113, USA. ; Tel: 847-467-3347.
authors.forename: Sonbinh T
authors.initials: ST
authors.lastname: Nguyen