Cisplatin(IV)-fatty acid prodrug-bound albumin nanoparticles: In vitro, in silico, and in vivo evaluation in breast cancer therapy

IF 4.3 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2026-03-01 Epub Date: 2026-02-09 DOI:10.1016/j.nano.2026.102910

Oly Katari , Vivek Yadav , Rajkumar R , Prabha Garg , Sanyog Jain

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Abstract

The therapeutic outcome of cisplatin (CP) in triple-negative breast cancer (TNBC) is hindered by irreversible protein binding, systemic toxicities, and resistance development. Therefore, we synthesized three CP(IV) prodrugs of fatty acids (FAs) possessing reversible albumin binding to overcome these shortcomings. Among these, CP-OA depicted the most cytotoxicity in MDA-MB-231 and 4T1 cells, showing synergistic effect and potential dose reduction. Albumin nanoparticles of CP-OA (CP-OA NPs) were optimized using a Design of Experiments (DoE) approach, yielding a particle size of 189.6 nm, PDI 0.23, and 77.47% entrapment efficiency. CP-OA NPs showed improved drug loading, sustained release, enhanced apoptosis (∼5 folds), ROS generation (∼2 folds), and mitochondrial depolarization (∼6 folds). The in vivo studies portrayed reduction in tumor volume (5.64-folds), organ toxicities and hemolysis (6.18-folds) compared to marketed formulation. Overall, this study highlights the therapeutic potential of CP(IV) prodrug bound albumin nanoparticles in improving therapeutic efficacy and safety of CP in TNBC.

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顺铂(IV)-脂肪酸前药结合白蛋白纳米颗粒：体外、硅和体内对乳腺癌治疗的评估。

顺铂（CP）治疗三阴性乳腺癌（TNBC）的疗效受到不可逆蛋白结合、全身毒性和耐药性发展的阻碍。因此，我们合成了三种具有可逆白蛋白结合的脂肪酸（FAs） CP（IV）前药来克服这些缺点。其中，CP-OA对MDA-MB-231和4T1细胞的细胞毒性最大，具有协同作用和潜在的剂量降低作用。采用实验设计（Design of Experiments, DoE）的方法对CP-OA白蛋白纳米颗粒（CP-OA NPs）进行了优化，得到粒径为189.6 nm， PDI为0.23，包封效率为77.47%。CP-OA NPs的载药量、缓释、细胞凋亡（~5倍）、ROS生成（~2倍）和线粒体去极化（~6倍）增强。体内研究显示，与上市制剂相比，肿瘤体积（5.64倍）、器官毒性和溶血（6.18倍）减少。总之，本研究强调了CP（IV）前药结合白蛋白纳米颗粒在提高TNBC中CP的疗效和安全性方面的治疗潜力。

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

Nanomedicine : nanotechnology, biology, and medicine 工程技术-纳米科技

CiteScore

11.10

自引率

0.00%

发文量

133

审稿时长

42 days

期刊介绍： The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.