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用于体外药物递送的邻苯二酚共轭白蛋白纳米颗粒制备的高碘酸盐介导的交联反应

Periodate-Mediated Cross-Linking for the Preparation of Catechol Conjugated Albumin Nanoparticles Used for in Vitro Drug Delivery.

作者信息

Argitekin Eda, Erez Ozlem, Cakan-Akdogan Gulcin, Akdogan Yasar

机构信息

Materials Science and Engineering Department, Izmir Institute of Technology, Izmir 35430, Turkey.

Izmir Biomedicine and Genome Center, 35340 Izmir, Turkey.

出版信息

ACS Appl Bio Mater. 2025 Mar 17;8(3):2182-2193. doi: 10.1021/acsabm.4c01737. Epub 2025 Feb 14.

DOI:10.1021/acsabm.4c01737
PMID:39950848
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11931531/
Abstract

Conjugation of serum albumin protein with catechol-containing dopamine molecules provides an alternative method for the preparation of albumin nanoparticles (NPs). A commonly used desolvation method utilizes glutaraldehyde as a cross-linking agent. Here, the catechol cross-linking mechanism is used instead of glutaraldehyde providing advantages to prevent toxicity and an undesirable reaction of glutaraldehyde with cargo molecules. Covalent cross-linking between dopamine conjugated bovine serum albumin (D-BSA) proteins was obtained in the presence of sodium periodate (NaIO) as an oxidizer. As a result, spherical D-BSA NPs with a uniform size distribution of around 100 nm in diameter and negative zeta potential around -28 mV were prepared. Optimal conditions were reached when a dopamine:IO molar ratio of 2:1, pH 7.4 of the medium, and acetone as the desolvating agent were used. Furthermore, the obtained NPs display antioxidant properties, have rapid biodegradability in the presence of trypsin, and have a high doxorubicin (DOX) loading (9.1%) with a sustainable drug release. DOX loaded D-BSA NPs also caused up to 90% breast cancer cell (MCF-7) death within 24 h. These results show that drug carrying albumin NPs can alternatively be prepared via covalently cross-linked catechol groups and used in drug delivery studies.

摘要

血清白蛋白与含儿茶酚的多巴胺分子结合为白蛋白纳米颗粒(NPs)的制备提供了一种替代方法。一种常用的去溶剂化方法利用戊二醛作为交联剂。在此,使用儿茶酚交联机制代替戊二醛,具有防止毒性以及避免戊二醛与负载分子发生不良反应的优势。在作为氧化剂的高碘酸钠(NaIO)存在下,实现了多巴胺共轭牛血清白蛋白(D-BSA)蛋白之间的共价交联。结果,制备出了直径约100 nm、尺寸分布均匀且zeta电位约为 -28 mV的球形D-BSA NPs。当多巴胺与高碘酸钠的摩尔比为2:1、介质pH值为7.4且使用丙酮作为去溶剂化剂时,达到了最佳条件。此外,所获得的NPs具有抗氧化性能,在胰蛋白酶存在下具有快速的生物降解性,并且具有高阿霉素(DOX)负载量(9.1%)以及可持续的药物释放。负载DOX的D-BSA NPs在24小时内还导致高达90%的乳腺癌细胞(MCF-7)死亡。这些结果表明,载药白蛋白NPs可以通过共价交联的儿茶酚基团来替代制备,并用于药物递送研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f4e/11931531/153f8094aa9f/mt4c01737_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f4e/11931531/8a6f4d359710/mt4c01737_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f4e/11931531/fad2b92da53d/mt4c01737_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f4e/11931531/e4e23a7c221d/mt4c01737_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f4e/11931531/6134e91e91e5/mt4c01737_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f4e/11931531/4b92b51536f3/mt4c01737_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f4e/11931531/ffafe13ef63a/mt4c01737_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f4e/11931531/153f8094aa9f/mt4c01737_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f4e/11931531/8a6f4d359710/mt4c01737_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f4e/11931531/fad2b92da53d/mt4c01737_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f4e/11931531/e4e23a7c221d/mt4c01737_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f4e/11931531/6134e91e91e5/mt4c01737_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f4e/11931531/4b92b51536f3/mt4c01737_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f4e/11931531/ffafe13ef63a/mt4c01737_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f4e/11931531/153f8094aa9f/mt4c01737_0007.jpg

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