Synthesis and in vitro activity of ROMP-based polymer nanoparticles

Dee Dee Smith, Sandra H. Clark, Paul A. Bertin, Bernard L. Mirkin, Sonbinh T. Nguyen

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2159-2165
Number of pages7
JournalJournal of Materials Chemistry
Volume19
Issue number15
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Chemistry

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