Efficient, dual-stimuli responsive cytosolic gene delivery using a RGD modified disulfide-linked polyethylenimine functionalized gold nanorod.
Efficient, dual-stimuli responsive cytosolic gene delivery using a RGD modified disulfide-linked polyethylenimine functionalized gold nanorod.
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DOI：
10.1016/j.jconrel.2014.09.026
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发表时间：
2014-12
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影响因子：
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通讯作者：
Feihu Wang;Yuanyuan Shen;Wenjun Zhang;Min Li;Yun Wang;Dejian Zhou;Shengrong Guo
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文献类型：
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作者：
Feihu Wang;Yuanyuan Shen;Wenjun Zhang;Min Li;Yun Wang;Dejian Zhou;Shengrong Guo
能够响应外部刺激和/或独特的内部环境的控释系统在位点特异性基因和/或药物递送方面受到极大的关注。在这项工作中，一个功能化的基因纳米载体的双刺激触发的胞质基因传递的发展，并显示出高的基因传递效率与低细胞毒性。通过将金纳米棒（GNR）与多个二硫键交联的短PEI缀合来制备纳米载体，以利用基于GNR的近红外（NIR）激光诱导的光热加热和二硫键交联的短PEI（DSPEI）的细胞内刺激触发的降解性的有利性质。DSPEI进一步接枝有聚（乙二醇）（PEG）部分，以提供在细胞培养物中的高载体稳定性和用于特异性靶向癌细胞的末端RGD肽。发现纳米载体有效地浓缩质粒DNA以形成高度稳定的GNR-DSPEI-PEG-RGD/DNA复合物，其具有肿瘤细胞靶向能力，可以被癌细胞有效地摄取。此外，负载的基因可以有效地从复合物中释放触发的高细胞内谷胱甘肽含量和/或通过光热效应的近红外线照射在808 nm。有趣的是，基于GNRs的复合物可以容易地从细胞内的内/溶酶体区室中逃逸，并在暴露于NIR照射时将基因负载释放到细胞溶质中，从而显著提高基因转染效率。我们的新基因载体具有高的基因转染效率，与高分子量PEI相当或甚至更好，但具有低得多的细胞毒性。此外，基于GNR的载体和激光治疗都没有显示出任何显著的细胞毒性证据。本工作为细胞内刺激触发、光热可控的基因传递系统提供了一种很有前途的策略，可进一步应用于许多其他纳米医学领域。
Controlled-release systems capable of responding to external stimuli and/or unique internal environments have received great interests in site-specific gene and/or drug delivery. In this work, a functionalized gene nanocarrier for dual-stimuli triggered cytosolic gene delivery is developed and showing high gene delivery efficacy with low cytotoxicity. The nanocarrier is prepared by conjugating gold nanorod (GNR) with multiple disulfide cross-linked short PEIs to harness the advantageous properties of GNR based near infrared (NIR) laser induced photothermal heating and intracellular stimuli-triggered degradability of disulfide cross-linked short PEIs (DSPEI). The DSPEI is further grafted with a poly(ethylene glycol) (PEG) section to afford high carrier stability in cell cultures and a terminal RGD peptide for specific targeting of cancer cells. The nanocarrier is found to effectively condense plasmid DNA to form a highly stable GNR-DSPEI-PEG-RGD/DNA complex with tumor cell-targeting ability that can be efficiently uptaken by cancer cells. Moreover, the loaded genes can be effectively released from the complex triggered by the high intracellular glutathione content and/or by photothermal effect of NIR irradiation at 808 nm. Interestingly, the GNRs-based complex can easily escape from intracellular endo-/lyso-somal compartments and release the gene load into the cytosol upon exposure to NIR irradiation, resulting in significantly improved gene transfection efficiency. Our new gene carrier exhibits high gene transfection efficiency, comparable to or even better than that of high MW PEIs, but with a much lower cytotoxicity. Additionally, neither the GNR-based carrier nor the laser treatment shows any significant evidence of cytotoxicity. This work demonstrates a promising strategy for intracellular stimuli triggered, photothermal controllable gene delivery system, which can be further applied to many other nanomedicine fields.