Photo-inducible crosslinked nanoassemblies for pH-controlled drug release.

Photo-inducible crosslinked nanoassemblies for pH-controlled drug release.
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DOI:
10.1007/s11095-013-1246-6
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发表时间:
2014-05
影响因子:
3.7
通讯作者:
Bae, Younsoo
Bae, Younsoo
中科院分区:
医学3区
文献类型:
--
作者:
Dickerson, Matthew;Winquist, Nickolas;Bae, Younsoo

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通过改变光交联程度和包含酸敏感连接体来控制嵌段共聚物纳米组装体的药物释放。制备了聚乙二醇-聚肉桂酸酯-酰肼-肉桂酸酯嵌段共聚物(PEG-CNM),并通过酸敏感性腙连接体与模型药物阿霉素(DOX)偶联。嵌段共聚物形成光诱导的自组装纳米组装体(piSNA),其用于通过UV交联产生光诱导的交联纳米组装体(piCNA)。纳米组装体的特征在于确定粒径,表面电荷,pH和交联依赖性DOX释放,体外细胞毒性,和细胞内摄取作为光交联度的函数。成功地制备了具有不同光交联度的纳米组装体,同时保留了粒径和表面电荷。光交联在pH 7.4下没有引起DOX从纳米组装体释放的明显变化,但是DOX负载的纳米组装体在pH 6.0下调节药物释放作为交联的函数。无论交联程度如何,纳米组装体均显示出相似的细胞毒性,这可能是由于低细胞摄取和细胞核药物蓄积。光交联可用于控制药物从pH敏感性嵌段共聚物纳米组装体中释放,作为交联的函数,而不改变颗粒性质,从而提供独特的工具来研究药物释放对细胞反应的药物作用。
To control drug release from block copolymer nanoassemblies by variation in the degree of photo-crosslinking and inclusion of acid sensitive linkers. Poly(ethylene glycol)-poly(aspartate-hydrazide-cinnamate) (PEG-CNM) block copolymers were prepared and conjugated with a model drug, doxorubicin (DOX), through acid sensitive hydrazone linkers. The block copolymers formed photo-inducible, self-assembled nanoassemblies (piSNAs), which were used to produce photo-inducible crosslinked nanoassemblies (piCNAs) through UV crosslinking. The nanoassemblies were characterized to determine particle size, surface charge, pH- and crosslinking-dependent DOX release, in vitro cytotoxicity, and intracellular uptake as a function of photo-crosslinking degree. Nanoassemblies with varying photo-crosslinking degrees were successfully prepared while retaining particle size and surface charge. Photo-crosslinking caused no noticeable change in DOX release from the nanoassemblies at pH 7.4, but the DOX-loaded nanoassemblies modulated drug release as a function of crosslinking at pH 6.0. The nanoassemblies showed similar cytotoxicity regardless of crosslinking degrees, presumably due to the low cellular uptake and cell nucleus drug accumulation. Photo-crosslinking is useful to control drug release from pH-sensitive block copolymer nanoassemblies as a function of crosslinking without altering the particle properties, and thus providing unique tools to investigate the pharmaceutical effects of drug release on cellular response.
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