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多功能绿色合成的 Cu-Al 层状双氢氧化物(LDH)纳米粒子:抗癌和抗菌活性。

Multifunctional green synthesized Cu-Al layered double hydroxide (LDH) nanoparticles: anti-cancer and antibacterial activities.

机构信息

Department of Chemistry, Sharif University of Technology, Tehran, Iran.

Center for Materials Interfaces, Istituto Italiano di Tecnologia, viale Rinaldo Piaggio 34, 56025, Pontedera, Pisa, Italy.

出版信息

Sci Rep. 2022 Jun 8;12(1):9461. doi: 10.1038/s41598-022-13431-7.

Abstract

Doxorubicin (DOX) is a potent anti-cancer agent and there have been attempts in developing nanostructures for its delivery to tumor cells. The nanoparticles promote cytotoxicity of DOX against tumor cells and in turn, they reduce adverse impacts on normal cells. The safety profile of nanostructures is an important topic and recently, the green synthesis of nanoparticles has obtained much attention for the preparation of biocompatible carriers. In the present study, we prepared layered double hydroxide (LDH) nanostructures for doxorubicin (DOX) delivery. The Cu-Al LDH nanoparticles were synthesized by combining Cu(NO)·3HO and Al(NO)·9HO, and then, autoclave at 110. The green modification of LDH nanoparticles with Plantago ovata (PO) was performed and finally, DOX was loaded onto nanostructures. The FTIR, XRD, and FESEM were employed for the characterization of LDH nanoparticles, confirming their proper synthesis. The drug release study revealed the pH-sensitive release of DOX (highest release at pH 5.5) and prolonged DOX release due to PO modification. Furthermore, MTT assay revealed improved biocompatibility of Cu-Al LDH nanostructures upon PO modification and showed controlled and low cytotoxicity towards a wide range of cell lines. The CLSM demonstrated cellular uptake of nanoparticles, both in the HEK-293 and MCF-7 cell lines; however, the results were showed promising cellular internalizations to the HEK-293 rather than MCF-7 cells. The in vivo experiment highlighted the normal histopathological structure of kidneys and no side effects of nanoparticles, further confirming their safety profile and potential as promising nano-scale delivery systems. Finally, antibacterial test revealed toxicity of PO-modified Cu-Al LDH nanoparticles against Gram-positive and -negative bacteria.

摘要

多柔比星(DOX)是一种有效的抗癌药物,人们一直在尝试开发纳米结构将其递送到肿瘤细胞中。这些纳米颗粒促进了 DOX 对肿瘤细胞的细胞毒性,进而降低了对正常细胞的不良影响。纳米结构的安全性是一个重要的课题,最近,纳米颗粒的绿色合成因其能够制备生物相容性载体而受到了广泛关注。在本研究中,我们制备了层状双氢氧化物(LDH)纳米结构用于递送多柔比星(DOX)。通过将 Cu(NO)·3HO 和 Al(NO)·9HO 结合,合成了 Cu-Al LDH 纳米颗粒,然后在 110°C 下进行高压釜处理。通过绿色修饰方法用车前草(PO)对 LDH 纳米颗粒进行修饰,最后将 DOX 加载到纳米结构上。通过傅里叶变换红外光谱(FTIR)、X 射线衍射(XRD)和场发射扫描电子显微镜(FESEM)对 LDH 纳米颗粒进行了表征,证实了其正确的合成。药物释放研究表明 DOX 具有 pH 敏感性释放(在 pH 5.5 时释放最高),并且由于 PO 修饰而延长了 DOX 的释放。此外,MTT 测定表明,PO 修饰后 Cu-Al LDH 纳米结构的生物相容性得到了改善,并且对广泛的细胞系表现出了控制和低细胞毒性。共聚焦激光扫描显微镜(CLSM)显示了纳米颗粒在 HEK-293 和 MCF-7 细胞系中的细胞摄取;然而,结果表明,与 MCF-7 细胞相比,HEK-293 细胞的细胞内摄取更有前景。体内实验突出了肾脏的正常组织病理学结构,并且纳米颗粒没有副作用,进一步证实了其安全性和作为有前途的纳米级递药系统的潜力。最后,抗菌试验表明 PO 修饰的 Cu-Al LDH 纳米颗粒对革兰氏阳性菌和革兰氏阴性菌具有毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e89c/9177833/0aba1c38dfa8/41598_2022_13431_Sch1_HTML.jpg

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