Improving Chemotherapy Effectiveness: Utilizing CuS Nanoparticles Coated with AS1411 Aptamer and Chitosan for Targeted Delivery of Doxorubicin to Cancerous Cells

被引:1
作者
Imanimoghadam, Maryam [1 ]
Yaghoobi, Elnaz [2 ,3 ]
Alizadeh, Fatemeh [1 ]
Ramezani, Mohammad [2 ]
Alibolandi, Mona [2 ]
Abnous, Khalil [2 ,4 ]
Taghdisi, Seyed Mohammad [5 ,6 ]
机构
[1] Mashhad Univ Med Sci, Sch Pharm, Mashhad, Iran
[2] Mashhad Univ Med Sci, Pharmaceut Technol Inst, Pharmaceut Res Ctr, Mashhad, Iran
[3] Univ Ottawa, Dept Chem & Biomol Sci, 10 Marie Curie, Ottawa, ON K1N 6N5, Canada
[4] Mashhad Univ Med Sci, Sch Pharm, Dept Med Chem, Mashhad, Iran
[5] Mashhad Univ Med Sci, Pharmaceut Technol Inst, Targeted Drug Delivery Res Ctr, Mashhad, Iran
[6] Mashhad Univ Med Sci, Sch Pharm, Dept Pharmaceut Biotechnol, Mashhad, Iran
关键词
Cancer treatment; Targeted drug delivery; CuS nanoparticle; Doxorubicin; AS1411; aptamer; DRUG-DELIVERY; IN-VITRO; TOXICITY; EFFICACY; THERAPY;
D O I
10.1016/j.xphs.2024.02.005
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Here, a novel targeted nanostructure complex was designed as an alternative to the traditional treatment approaches for breast cancer. A delivery system utilizing CuS nanoparticles (CuS NPs) was developed for the purpose of targeted administration of doxorubicin (Dox), an anticancer agent. To regulate Dox release, chitosan (CS), a biodegradable and hydrophilic polymer with biocompatible properties, was applied to coat the Dox-loaded CuS NPs. Furthermore, AS1411 aptamer, served as a targeting agent for breast cancer cells (MCF7 and 4T1 cells), was conjugated with CS-Dox-CuS NPs effectively. To assess the effectiveness of APT-CS-CuS NPs, various methods such as flow cytometry analysis, MTT assay, fluorescence imaging, and in vivo antitumor efficacy were employed. The hollow core and porous surface of CuS NPs improved the Dox loading capacity and entrapment efficiency (almost 100%). The rate of drug release at the tumor site (citrate buffer with pH 5.6) exhibited a marked increase in comparison to that observed within the physiological environment (phosphate buffer with pH 7.4). The targeted formulation (APT-CS-Dox-CuS NPs) significantly increased cytotoxicity of the Dox payload in target cells, including 4T1 (p <= 0.0001 (****)) and MCF7 (p <= 0.01 (**)) cells compared to CHO cells. Moreover, the ability of tumor growth inhibition of the targeted system was significantly (p <= 0.05 (*)) more than free Dox in tumor-bearing mice. The findings indicate that the targeted formulation augmented effectiveness and specificity while minimizing harm to non-targeted cells, signifying its potential as a sophisticated cancer drug delivery system. (c) 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:1865 / 1873
页数:9
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