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

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials 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

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464