MRI-visible micellar nanomedicine for targeted drug delivery to lung cancer cells.
MRI-visible micellar nanomedicine for targeted drug delivery to lung cancer cells.
复制标题
DOI：
10.1021/mp9001393
复制
发表时间：
2010-02-01
影响因子：
4.9
通讯作者：
Gao J
中科院分区：
文献类型：
--
作者：
Guthi JS;Yang SG;Huang G;Li S;Khemtong C;Kessinger CW;Peyton M;Minna JD;Brown KC;Gao J
聚合物胶束正在成为一种高度集成的纳米平台，用于癌症靶向、药物传递和肿瘤成像应用。在这项研究中，我们描述了一个多功能胶束（MFM）系统，该系统由肺癌靶向肽（LCP）编码，并被超顺磁性氧化铁（SPIO）和阿霉素（Doxo）包裹，分别用于磁共振成像和治疗递送。lcp编码的MFM在H2009肺癌细胞中的αvβ6依赖性细胞靶向性明显高于重组肽（SP）编码的MFM对照和αvβ6阴性的H460细胞对照。利用3h标记的MFM纳米颗粒，量化不同肽编码（LCP vs SP）和表面密度（20%和40%）的MFM纳米颗粒在H2009细胞中的细胞摄取随时间和剂量的依赖性。与SP相比，胶束表面LCP功能化使MFM的吸收量增加了3倍以上。这些结果在激光共聚焦扫描显微镜下得到了证实，进一步证实了Doxo从MFM中成功释放并在细胞核中积累。SPIO在胶束核心内的聚集导致了高的T2弛豫度（>400 Fe mM−1 s−1）。t2加权MRI图像显示，用lcp编码的MFM孵育的H2009细胞与用sp编码的MFM孵育的H2009细胞之间存在明显的对比差异。ATP活性测定显示，lcp编码的MFM在H2009细胞中的细胞毒性高于sp编码的MFM （IC50值分别为28.3±6.4 nM和73.6±6.3 nM, p < 0.005）。MFM纳米医学的综合诊断和治疗设计可能允许图像引导，靶向特异性治疗肺癌。
Polymeric micelles are emerging as a highly integrated nanoplatform for cancer targeting, drug delivery and tumor imaging applications. In this study, we describe a multifunctional micelle (MFM) system that is encoded with a lung cancer-targeting peptide (LCP), and encapsulated with superparamagnetic iron oxide (SPIO) and doxorubicin (Doxo) for MR imaging and therapeutic delivery, respectively. The LCP-encoded MFM showed significantly increased αvβ6-dependent cell targeting in H2009 lung cancer cells over a scrambled peptide (SP)-encoded MFM control as well as in an αvβ6-negative H460 cell control. 3H-Labeled MFM nanoparticles were used to quantify the time- and dose-dependent cell uptake of MFM nanoparticles with different peptide encoding (LCP vs SP) and surface densities (20% and 40%) in H2009 cells. LCP functionalization of the micelle surface increased uptake of the MFM by more than 3-fold compared to the SP control. These results were confirmed by confocal laser scanning microscopy, which further demonstrated the successful Doxo release from MFM and accumulation in the nucleus. SPIO clustering inside the micelle core resulted in high T2 relaxivity (>400 Fe mM−1 s−1) of the resulting MFM nanoparticles. T2-weighted MRI images showed clear contrast differences between H2009 cells incubated with LCP-encoded MFM over the SP-encoded MFM control. An ATP activity assay showed increased cytotoxicity of LCP-encoded MFM over SP-encoded MFM in H2009 cells (IC50 values were 28.3 ± 6.4 nM and 73.6 ± 6.3 nM, respectively; p < 0.005). The integrated diagnostic and therapeutic design of MFM nanomedicine potentially allows for image-guided, target-specific treatment of lung cancer.
登录
查看更多内容
影响因子：
4.7
作者：
Guan H;McGuire MJ;Li S;Brown KC
通讯作者：
Brown KC
DOI：
10.3181/0808-mr-250
发表时间：
2009-02
期刊：
Experimental biology and medicine (Maywood, N.J.)
影响因子：
--
作者：
Blanco E;Kessinger CW;Sumer BD;Gao J
通讯作者：
Gao J
影响因子：
2.8
作者：
Kawashima, A;Tsugawa, S;Oda, Y
通讯作者：
Oda, Y
影响因子：
10.8
作者：
Nasongkla, Norased;Bey, Erik;Gao, Jinming
通讯作者：
Gao, Jinming
影响因子：
9.7
作者：
Oyama, T;Sykes, KF;Brown, KC
通讯作者：
Brown, KC