Doxorubicin-sanguinarine nanoparticles: formulation and evaluation of breast cancer cell apoptosis and cell cycle.

IF 2.4 4区医学 Q3 CHEMISTRY, MEDICINAL

Drug Development and Industrial Pharmacy Pub Date : 2024-01-05 DOI:10.1080/03639045.2024.2302557

Mahmoud Zaki El-Readi, Majed Abdurhman Abdulkarim, Ahmed A H Abdellatif, Mohamed E Elzubeir, Bassem Refaat, Mohammad Althubiti, Riyad Adnan Almaimani, Mohammed Hasan Mukhtar, Issa Saad Al-Moraya, Safaa Yehia Eid

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引用次数: 0

Abstract

Background: Therapeutic resistance fails cancer treatment. Drug-nanoparticle combinations overcome resistance. Sanguinarine-conjugated nanoparticles may boost sanguinarine's anticancer effects.

Methods: Sanguinarine, HPMC-NPs, and doxorubicin were tested on Adriamycin-resistant MCF-7/ADR breast cancer cells, parent-sensitive MCF-7, and MCR-5 normal cells (DX).

Results: Regular distribution, 156 nm diameter, <1 μm average size, 100% intensity-SN is therapeutic. Furthermore, the obtained NPs showed PDI = 0.145, zeta-potential=-37.6, and EE%=90.5%. DX sensitized MCF-7 cells (IC₅₀ = 1.4 μM) more than MCF-7/ADR cells (IC₅₀ = 27 μM) with RR = 19.3. SA and SN were more toxic to MCF-7/ADR cells (overexpressed with P-gp) than their sensitive parent MCF-7 cells (IC₅₀ = 4 μM, RR = 0.6 and 0.6 μM, RR = 0.7). MCR-5 normal lung cells were more resistant to SA (IC₅₀ = 7.2 μM) and SN (IC₅₀ = 1.6 μM) with a selection index > 2. Synergistic cytotoxic interactions reduced the IC₅₀ from 27 μM to 1.6 (CI = 0.1) and 0.9 (CI = 0.4) after DX and nontoxic dosages (IC₂₀) of SA and SN. DS and SN killed 27.1% and 39.4% more cells than DX (7.7%), SA (4.9%), SN (5.5%), or untreated control (0.3%). DS and DSN lowered CCND1 and survival in MCF-7/ADR cells while raising p21 and Casp3 gene and protein expression.

Conclusions: Cellular and molecular studies suggested adjuvant chemosensitizers SA and SN to reverse MDR in breast cancer cells.

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多柔比星-鞘氨醇纳米颗粒：乳腺癌细胞凋亡和细胞周期的制备与评估

背景抗药性使癌症治疗失败。药物-纳米颗粒组合可克服抗药性。与番木瓜碱结合的纳米粒子可增强番木瓜碱的抗癌效果。方法在对阿霉素耐药的 MCF-7/ADR 乳腺癌细胞、对母体敏感的 MCF-7 细胞和 MCR-5 正常细胞（DX）上测试桑吉纳林、HPMC-NPs 和多柔比星。结果显示MCF-7/ADR细胞（IC50=27 μM）比MCF-7/ADR细胞（IC50=1.4 μM）毒性更强，RR=19.3。与敏感的母体 MCF-7 细胞相比，SA 和 SN 对 MCF-7/ADR 细胞（过表达 P-gp）的毒性更大（IC50=4 μM，RR=0.6 和 0.6 μM，RR=0.7）。MCR-5 正常肺细胞对 SA（IC50=7.2 μM）和 SN（IC50=1.6 μM）的耐药性更强，选择指数大于 2。SA和SN的DX和无毒剂量（IC20）后，协同细胞毒性相互作用将IC50从27 μM降低到1.6（CI = 0.1）和0.9（CI = 0.4）。与 DX（7.7%）、SA（4.9%）、SN（5.5%）或未处理的对照组（0.3%）相比，DS 和 SN 杀死的细胞分别多 27.1% 和 39.4%。DS 和 DSN 降低了 MCF-7/ADR 细胞的 CCND1 和存活率，同时提高了 p21 和 Casp3 基因和蛋白的表达。结论细胞和分子研究表明，辅助化疗增敏剂 SA 和 SN 可逆转乳腺癌细胞的 MDR。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Development and Industrial Pharmacy 医学-药学

CiteScore

6.80

自引率

0.00%

发文量

审稿时长

4.5 months

期刊介绍： The aim of Drug Development and Industrial Pharmacy is to publish novel, original, peer-reviewed research manuscripts within relevant topics and research methods related to pharmaceutical research and development, and industrial pharmacy. Research papers must be hypothesis driven and emphasize innovative breakthrough topics in pharmaceutics and drug delivery. The journal will also consider timely critical review papers.