Modified sodium caseinate-based nanomicelles for enhanced chemotherapeutics against breast cancer via improved cellular uptake and cytotoxicity.

IF 2.4 4区医学 Q3 CHEMISTRY, MEDICINAL

Drug Development and Industrial Pharmacy Pub Date : 2025-07-01 Epub Date: 2025-05-02 DOI:10.1080/03639045.2025.2495849

Farah Rehan, Md Emranul Karim, Nafees Ahemad, Omer Salman Qureshi, Seemal Jelani, Siew Hua Gan, Ezharul Hoque Chowdhury

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引用次数: 0

Abstract

Objective: Poor prognosis, drug resistance, and lower drug loading capacity of the delivery systems lead to therapeutic failures of breast cancers. Herein, we functionalized sodium caseinate nanomicelles (NaCNs) with the divalent calcium (Ca²⁺) and the glucose (Glc) to increase the loading capacity of micelles for higher cellular uptake and cytotoxicity against breast cancer cells.

Methodology: Modification of casein micelles was confirmed through Fourier transform infrared spectra (FTIR). Triple quadrupole liquid chromatography-mass spectrometry (TQOF-LCMS/MS) was utilized as a simple, rapid, and sensitive method for protein corona quantification around casein through SwissProt.Mus_musculus database and through de novo sequencing. Un-modified and modified casein micelles were further characterized through field emission scanning electron microscope (FESEM), high resolution-transmission electron microscope (HR-TEM), and energy-dispersive X-ray (EDX). Whereas, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used for protein separation and analysis during micelles formation.

Results: Calcium divalent modified sodium caseinate nanomicelles (Ca-NaCNs) and glucose-modified sodium caseinate nanomicelles (Glc-NaCNs) were successfully developed, demonstrating a significantly improved micellar stability. Glc-NaCNs-DOX showed a zeta size of 297.13 ± 15.66 nm with an improved zeta potential of -13.73 ± 0.579 with a drug loading efficiency (DLE) of 86% as compared to our previously published casein formulations since the modified versions involved more soluble casein in the protein micelle matrix, Whereas, Ca-NaCNs-DOX also showed an IC₅₀ value of approximately 197.1 nm as compared to IC₅₀ of free DOX (341.8 nm) and when compared to unmodified DOX loaded formulations (p < .001).

Conclusion: Modified NaCNs exhibit the potential to be investigated further as a novel delivery system for similar active moieties to maximize their therapeutic effects.

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改良酪氨酸钠基纳米胶束通过改善细胞摄取和细胞毒性增强乳腺癌化疗药物。

目的：乳腺癌输注系统预后差、耐药、载药能力低是导致乳腺癌治疗失败的主要原因。在这里，我们用二价钙（Ca2+）和葡萄糖（Glc）功能化酪蛋白酸钠纳米胶束（NaCNs），以增加胶束的负载能力，从而提高细胞摄取和对乳腺癌细胞的细胞毒性。方法：利用傅里叶变换红外光谱（FTIR）证实酪蛋白胶束的修饰。三重四极柱液相色谱-质谱法（TQOF-LCMS/MS）是一种简单、快速、灵敏的方法，可通过SwissProt对酪蛋白周围的蛋白冠进行定量分析。mus_musus数据库，并通过从头测序。通过场发射扫描电镜（FESEM）、高分辨率透射电镜（HR-TEM）和能量色散x射线（EDX）进一步表征了未修饰和修饰的酪蛋白胶束。而用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）对胶束形成过程中的蛋白质进行分离和分析。结果：成功制备了钙二价修饰酪蛋白酸钠纳米胶束（Ca-NaCNs）和葡萄糖修饰酪蛋白酸钠纳米胶束（Glc-NaCNs），胶束稳定性显著提高。与我们之前发表的酪蛋白配方相比，Glc-NaCNs-DOX的zeta尺寸为297.13±15.66 nm， zeta电位为-13.73±0.579，载药效率（DLE）为86%，因为修饰后的版本在蛋白质胶束基质中含有更多可溶性酪蛋白。然而，Ca-NaCNs-DOX的IC50值也约为197.1 nm，与自由DOX的IC50值（341.8 nm）相比，与未修饰的DOX负载配方相比(p结论：修饰过的nacn作为一种新型的递送系统，有潜力被进一步研究，以最大限度地发挥其治疗效果。

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.