Synthesis and In vitro activity of ROMP-based polymer nanoparticles.

Deedee Smith, Sandra H Clark, Paul A Bertin, Bernard L Mirkin, Sonbinh T Nguyen
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引用次数: 25

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.

romp基纳米聚合物的合成及体外活性研究。
制备了一种含有高密度共价连接阿霉素的新型聚合物纳米颗粒(PNP),其通过不可切割的胺键连接(胺链Dox-PNP)。与先前报道的可切割氨基甲酸酯连接的Dox-PNP一起,这种新的胺连接的Dox-PNP随后被评估了对游离阿霉素的细胞毒性和对SKNSH野生型和SKrDOX6阿霉素耐药的人神经母细胞瘤细胞系的抑制作用。同时合成了类似的含胆固醇PNPs (choll -PNPs)和含吲哚美辛PNPs (IND-PNPs)作为无细胞毒性对照。虽然没有细胞系受到胆- pnps或IND-PNPs的影响,但SKrDOX6抗阿霉素细胞对游离阿霉素和胺和氨基甲酸酯连接的阿霉素- pnps表现出类似的细胞毒性反应,这表明阿霉素或含阿霉素的聚合物在后者的情况下必须是活性剂。SKNSH野生型细胞也对这两种Dox-PNPs有反应,尽管其表观浓度高于单独使用游离阿霉素。氨基甲酸酯连接的Dox-PNPs与游离阿霉素孵育7天后,SKNSH野生型细胞的生长明显受到抑制。与游离阿霉素相比,氨基甲酸酯连接的Dox-PNPs在SKrDOX6阿霉素耐药细胞中产生了更长的初始抑制期(72小时)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Materials Chemistry
Journal of Materials Chemistry 工程技术-材料科学:综合
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1.5 months
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