Fabrication and intracellular delivery of doxorubicin/carbonate apatite nanocomposites: effect on growth retardation of established colon tumor.
Fabrication and intracellular delivery of doxorubicin/carbonate apatite nanocomposites: effect on growth retardation of established colon tumor.
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DOI：
10.1371/journal.pone.0060428
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Akaike T
中科院分区：
文献类型：
--
作者：
Hossain S;Yamamoto H;Chowdhury EH;Wu X;Hirose H;Haque A;Doki Y;Mori M;Akaike T
在持续寻找有效的癌症治疗方法的过程中，新兴的模型旨在将治疗剂有效地细胞内递送到肿瘤细胞中以增加药物浓度。然而，这种策略的实施受到低效的细胞摄取和耐药性的影响。因此，最近开发了pH敏感纳米系统，以靶向固体肿瘤的微酸性细胞外pH环境。pH靶向方法被认为是比常规的特异性肿瘤细胞表面靶向方法更通用的策略，因为酸性肿瘤微气候在实体瘤中最常见。当纳米系统与内体或溶酶体酸性pH沿着的触发释放机制以及内体溶解能力组合时，纳米载体被证明克服各种肿瘤的多药耐药性。在这里，已经制造了新型pH敏感性碳酸磷灰石，以有效地将抗癌药物阿霉素（DOX）递送至癌细胞，这是由于其pH敏感性在内体中的酸性条件下非常不稳定，并且所得磷灰石-DOX的期望尺寸用于有效的细胞摄取，如通过扫描电子显微镜所揭示的。荧光显微镜和流式细胞仪分析表明，药物的显着摄取（92%）时，与磷灰石纳米粒子复合。体外药敏实验表明，与游离药物相比，apatite-DOX纳米粒对多种人癌细胞系具有较高的细胞毒性，并在BALB/cA裸鼠结直肠肿瘤模型中观察到apatite-DOX促进的肿瘤抑制作用，从而揭示了其在肿瘤治疗中的潜在应用。
In continuing search for effective treatments of cancer, the emerging model aims at efficient intracellular delivery of therapeutics into tumor cells in order to increase the drug concentration. However, the implementation of this strategy suffers from inefficient cellular uptake and drug resistance. Therefore, pH-sensitive nanosystems have recently been developed to target slightly acidic extracellular pH environment of solid tumors. The pH targeting approach is regarded as a more general strategy than conventional specific tumor cell surface targeting approaches, because the acidic tumor microclimate is most common in solid tumors. When nanosystems are combined with triggered release mechanisms in endosomal or lysosomal acidic pH along with endosomolytic capability, the nanocarriers demonstrated to overcome multidrug resistance of various tumors. Here, novel pH sensitive carbonate apatite has been fabricated to efficiently deliver anticancer drug Doxorubicin (DOX) to cancer cells, by virtue of its pH sensitivity being quite unstable under an acidic condition in endosomes and the desirable size of the resulting apatite-DOX for efficient cellular uptake as revealed by scanning electron microscopy. Florescence microscopy and flow cytometry analyses demonstrated significant uptake of drug (92%) when complexed with apatite nanoparticles. In vitro chemosensitivity assay revealed that apatite-DOX nanoparticles executed high cytotoxicity in several human cancer cell lines compared to free drugs and consequently apatite-DOX-facilitated enhanced tumor inhibitory effect was observed in colorectal tumor model within BALB/cA nude mice, thereby shedding light on their potential applications in cancer therapy.
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影响因子：
15
作者：
MAEDA, M;KUMANO, A;TIRRELL, DA
通讯作者：
TIRRELL, DA
影响因子：
10.8
作者：
Dharap, SS;Qiu, B;Minko, T
通讯作者：
Minko, T
DOI：
10.1073/pnas.0504274102
发表时间：
2005-09-06
影响因子：
11.1
作者：
Dharap, SS;Wang, Y;Minko, T
通讯作者：
Minko, T
影响因子：
3.5
作者：
Chowdhury, E. H.;Maruyama, A.;Akaike, T.
通讯作者：
Akaike, T.
影响因子：
4.9
作者：
Kim D;Gao ZG;Lee ES;Bae YH
通讯作者：
Bae YH