期刊
JOURNAL OF MATERIALS CHEMISTRY
卷 19, 期 15, 页码 2159-2165出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/b817511j
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资金
- National Institute of Health [NCI 1U54 CA119341-01]
- National Science Foundation [0094347, EEC-0647560, DMR-0520523]
- John W. Anderson Foundation
- North Suburban Medical Research Junior Board
- Medical Research Junior Board Foundation
- Medical Research Institute Council
- R. Wile Foundation
- Children's Memorial Research Center
- NSF-NSEC
- NSF-MRSEC
- Keck Foundation
- State of Illinois
- Northwestern University
- NATIONAL CANCER INSTITUTE [U54CA119341] Funding Source: NIH RePORTER
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.
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