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Hyaluronic acid-capped compact silica-supported mesoporous titania nanoparticles for ligand-directed delivery of doxorubicin
Acta Biomaterialia ( IF 9.7 ) Pub Date : 2018-09-08 , DOI: 10.1016/j.actbio.2018.09.006
Biki Gupta , Bijay Kumar Poudel , Hima Bindu Ruttala , Shobha Regmi , Shiva Pathak , Milan Gautam , Sung Giu Jin , Jee-Heon Jeong , Han-Gon Choi , Sae Kwang Ku , Chul Soon Yong , Jong Oh Kim

Mesoporous titania nanoparticles (MTN), owing to their high surface area to volume ratio and tunable pore sizes, appear capable of delivering sizable amounts of drug payloads, and hence, show considerable promise as drug delivery candidates in cancer therapy. We designed silica-supported MTN (MTNst) coated with hyaluronic acid (HA) to effectively deliver doxorubicin (DOX) for breast cancer therapy. The HA coating served a dual purpose of stabilizing the payload in the carriers as well as actively targeting the nanodevices to CD44 receptors. The so-formed HA-coated MTNst carrying DOX (HA/DOX-MTNst) had spheroid particles with a considerable drug-loading capacity and showed significantly superior in vitro cytotoxicity against MDA-MB-231 cells as compared to free DOX. HA/DOX-MTNst markedly improved the cellular uptake of DOX in an apparently CD44 receptor-dependent manner, and increased the number of apoptotic cells as compared to free DOX. These nanoplatforms accumulated in large quantities in the tumors of MDA-MB-231 xenograft tumor-bearing mice, where they significantly enhanced the inhibition of tumor growth compared to that observed with free DOX with no signs of acute toxicity. Based on these excellent results, we deduced that HA/DOX-MTNst could be successfully used for targeted breast cancer therapy.

Statement of significance

This is the first study to use silica-supported mesoporous titania nanoparticles (MTNst) for doxorubicin (DOX) delivery to treat breast cancer, which exhibited effective and enhanced in vitro and in vivo apoptosis and tumor growth inhibition. Solid silica was used to support the mesoporous TiO2 resulting in MTNst, which efficiently incorporated a high DOX payload. The hyaluronic acid (HA) coating over the MTNst surface served a dual purpose of first, stabilizing DOX inside the MTNst (capping agent), and second, directing the nanoplatform device to CD44 receptors that are highly expressed in MDA-MB-231 cells (targeting ligand). The NPs exhibited highly efficacious in vitro tumor-cell killing and excellent in vivo tumor regression, highlighting the enormous promise of this system for breast cancer therapy.



中文翻译:

透明质酸封端的紧凑型二氧化硅支撑的介孔二氧化钛纳米颗粒,用于阿霉素的配体定向递送

介孔二氧化钛纳米颗粒(MTN)由于其高的表面积与体积之比和可调节的孔径,似乎能够传递相当数量的药物有效载荷,因此,在癌症治疗中作为药物的候选药物具有广阔的前景。我们设计了涂有透明质酸(HA)的二氧化硅支持的MTN(MTNst),可有效递送阿霉素(DOX)用于乳腺癌治疗。HA涂层的双重作用是稳定载体中的有效载荷,并主动将纳米器件靶向CD44受体。如此形成的带有HA涂层的带有DOX的MTNst(HA / DOX-MTNst)具有球状颗粒,具有相当大的载药能力,并且与游离的DOX相比,对MDA-MB-231细胞显示出显着优越的体外细胞毒性。与游离的DOX相比,HA / DOX-MTNst以明显的CD44受体依赖性方式显着改善了DOX的细胞摄取,并增加了凋亡细胞的数量。这些纳米平台在带有MDA-MB-231异种移植肿瘤的小鼠的肿瘤中大量积累,与没有急性毒性迹象的游离DOX相比,它们显着增强了对肿瘤生长的抑制作用。基于这些出色的结果,我们推论HA / DOX-MTNst可以成功用于靶向乳腺癌治疗。与没有急性毒性迹象的游离DOX相比,它们显着增强了对肿瘤生长的抑制作用。基于这些出色的结果,我们推论HA / DOX-MTNst可以成功用于靶向乳腺癌治疗。与没有急性毒性迹象的游离DOX相比,它们显着增强了对肿瘤生长的抑制作用。基于这些出色的结果,我们推论HA / DOX-MTNst可以成功用于靶向乳腺癌治疗。

重要声明

这是第一项使用二氧化硅支持的介孔二氧化钛纳米颗粒(MTNst)输送阿霉素(DOX)来治疗乳腺癌的研究,该乳腺癌表现出有效和增强的体内外凋亡和肿瘤生长抑制作用。固体二氧化硅用于支撑介孔TiO 2,从而产生MTNst,该MTNst有效地掺入了高DOX负载。MTNst表面的透明质酸(HA)涂层具有双重目的:首先,稳定MTNst(封端剂)内部的DOX,其次,将纳米平台设备导向在MDA-MB-231细胞中高度表达的CD44受体(靶向配体)。NPs表现出高效的体外肿瘤细胞杀伤和出色的体内肿瘤消退,凸显了该系统在乳腺癌治疗中的巨大前景。

更新日期:2018-09-09
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