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低频磁场增强了等离子体修饰的磁电纳米颗粒的药物负载,从而提高了体外和体内的抗癌活性。

Low-frequency magnetic fields potentiate plasma-modified magneto-electric nanoparticle drug loading for anticancer activity in vitro and in vivo.

机构信息

Laser and Plasma Research Institute, Shahid Beheshti University, Tehran, Iran.

Leibniz Institute for Plasma Science and Technology (INP), Greifswald, Germany.

出版信息

Sci Rep. 2023 Oct 16;13(1):17536. doi: 10.1038/s41598-023-44683-6.

DOI:10.1038/s41598-023-44683-6
PMID:37845238
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10579258/
Abstract

A multiferroic nanostructure of manganese ferrite barium-titanate called magneto-electric nanoparticles (MENs) was synthesized by a co-precipitation method. FTIR, Raman spectroscopy, TEM, and X-ray diffraction confirmed the presence of spinel core and perovskite shell phases with average crystallite sizes of 70-90 nm. Magnetic, optical, and magnetoelectrical properties of MENs were investigated using VSM, UV-Vis spectrophotometry, DLS, and EIS spectroscopy techniques. After pre-activation by low-pressure argon (Ar) plasma, the MENs were functionalized by a highly hydrophilic acrylic acid and Oxygen (AAc+O) mixture to produce COOH and C=O-rich surfaces. The loading and release of doxorubicin hydrochloride (DOX) on MENs were investigated using UV-vis and fluorescence spectrophotometry under alternating low-frequency magnetic fields. Plasma treatment enabled drug-loading control by changing the particles' roughness as physical adsorption and creating functional groups for chemical absorption. This led to reduced metabolic activity and cell adherences associated with elevated expression of pro-apoptotic genes (BCL-2, caspase 3) in 4T1 breast cancer cells in vitro exposed to alternating current magnetic field (ACMF) compared to MENs-DOX without field exposure. ACMF-potentiated anticancer effects of MENs were validated in vivo in tumor-bearing Balb/C mice. Altogether, our results suggest potentiated drug loading of MENs showing superior anticancer activity in vitro and in vivo when combined with ACMF.

摘要

采用共沉淀法合成了一种称为磁电纳米粒子(MENs)的锰铁氧体钡钛酸盐多铁纳米结构。FTIR、拉曼光谱、TEM 和 X 射线衍射证实了具有平均晶粒尺寸为 70-90nm 的尖晶石核和钙钛矿壳相的存在。使用 VSM、UV-Vis 分光光度法、DLS 和 EIS 光谱技术研究了 MENs 的磁性、光学和磁电性能。在经过低压氩气(Ar)等离子体预处理后,通过高度亲水性的丙烯酸和氧(AAc+O)混合物对 MENs 进行功能化,以产生富含-COOH 和 C=O 的表面。通过在低频交变磁场下使用 UV-vis 和荧光分光光度法研究了 MENs 上盐酸多柔比星(DOX)的加载和释放。等离子体处理通过改变颗粒的粗糙度作为物理吸附和为化学吸收创造官能团来控制药物负载。这导致体外暴露于交流磁场(ACMF)的 4T1 乳腺癌细胞的代谢活性和细胞粘附降低,与未暴露于磁场的 MENs-DOX 相比,凋亡基因(BCL-2、caspase 3)的表达升高。在荷瘤 Balb/C 小鼠中体内验证了 MENs 与 ACMF 结合的抗肿瘤作用。总之,我们的研究结果表明,当与 ACMF 结合时,MENs 的药物负载能力增强,显示出体外和体内的优异抗肿瘤活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/b28b4a25099e/41598_2023_44683_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/86404b6bbf36/41598_2023_44683_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/50e387c79960/41598_2023_44683_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/5fb4ba202402/41598_2023_44683_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/428abcff6b53/41598_2023_44683_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/6d897d226733/41598_2023_44683_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/8afb1b070a69/41598_2023_44683_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/214563823616/41598_2023_44683_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/daa73369ee0c/41598_2023_44683_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/b28b4a25099e/41598_2023_44683_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/86404b6bbf36/41598_2023_44683_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/50e387c79960/41598_2023_44683_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/5fb4ba202402/41598_2023_44683_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/428abcff6b53/41598_2023_44683_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/6d897d226733/41598_2023_44683_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/8afb1b070a69/41598_2023_44683_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/214563823616/41598_2023_44683_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/daa73369ee0c/41598_2023_44683_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa6/10579258/b28b4a25099e/41598_2023_44683_Fig9_HTML.jpg

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