Synthesis and in vitro activity of ROMP-based polymer nanoparticles

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...

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Bibliographic Details
Published in:Journal of materials chemistry 2009-04, Vol.19 (15), p.2159-2165
Main Authors: SMITH, Deedee, CLARK, Sandra H, BERTIN, Paul A, MIRKIN, Bernard L, NGUYEN, Sonbinh T
Format: Article
Language:English
Subjects:
Applied sciences
Biological and medical sciences
Biotechnology
Cross-disciplinary physics: materials science
rheology
Exact sciences and technology
Forms of application and semi-finished materials
Fundamental and applied biological sciences. Psychology
Materials science
Methods. Procedures. Technologies
Miscellaneous
Nanocrystalline materials
Nanoscale materials and structures: fabrication and characterization
Others
Physics
Polymer industry, paints, wood
Technology of polymers
Various methods and equipments
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Summary: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.
ISSN:0959-9428
1364-5501
DOI:10.1039/b817511j