用于靶向治疗的隐形白蛋白包裹纳米粒子:异种移植-斑马鱼模型中的有效给药和肿瘤抑制。

IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY
International Journal of Nanomedicine Pub Date : 2024-12-10 eCollection Date: 2024-01-01 DOI:10.2147/IJN.S476241
Sara Bozzer, Maria Cristina Grimaldi, Luca De Maso, Marcello Manfredi, Giuseppe Toffoli, Michele Dal Bo, Daniele Sblattero, Paolo Macor
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引用次数: 0

摘要

目的:在血液中,纳米粒子(NPs)与血清蛋白相互作用,形成蛋白电晕,其中包括促进 NP 识别和清除的溶蛋白和可抑制溶蛋白活性的溶蛋白抑制剂。白蛋白是最丰富的血清蛋白,它也是这种电晕的一部分,可以充当溶血蛋白,有可能将 NP 隐藏在免疫系统之外。本研究旨在探讨在聚合物 NPs 上共价结合一层人血清白蛋白(HSA)会如何影响蛋白质电晕及其在免疫系统中的行为:我们将 HSA 共价连接到聚合物 NPs 表面,以改变蛋白质电晕的组成。然后用抗CD19重组抗体片段装饰这些HSA覆盖的纳米结构,以靶向恶性B细胞,特别是急性淋巴细胞白血病(ALL)细胞。使用人-斑马鱼异种移植 ALL 模型对这些靶向 HSA 纳米粒子的安全性和生物利用度进行了体外和体内评估。此外,还评估了纳米结构在递送封装多柔比星和抑制肿瘤生长方面的功效:结果:高分子纳米粒子上的HSA涂层有效地修饰了蛋白电晕,防止了蛋白的疏松和随后由巨噬细胞介导的清除。在异种移植模型中,靶向 HSA 纳米粒子保持了安全的特性,减少了与巨噬细胞的相互作用,并能特异性地靶向肿瘤细胞。这使得多柔比星的成功输送、肿瘤生长抑制和模型生物存活率的提高得以实现:该研究表明,HSA 涂层纳米颗粒可用作治疗纳米平台,具有安全的特性和更高的生物利用度。用特定的靶向药物(如抗 CD19 抗体)装饰这些纳米结构的能力为开发可针对各种临床病症的多功能治疗平台提供了可能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Stealth-Engineered Albumin-Coated Nanoparticles for Targeted Therapy: Effective Drug Delivery and Tumor Suppression in Xenograft-Zebrafish Model.

Purpose: In the bloodstream, nanoparticles (NPs) interact with serum proteins to form the protein corona, which includes both opsonins, promoting NP recognition and elimination, and dysopsonins, which can inhibit opsonin activity. Albumin, the most abundant serum protein, is part of this corona and can act as a dysopsonin, potentially hiding NPs from the immune system. This study aims to investigate how a covalently bound layer of human serum albumin (HSA) on polymeric NPs affects the protein corona and their behavior in the immune system.

Methods: We covalently attached HSA to the surface of polymeric NPs to modify the protein corona composition. These HSA-covered nanostructures were then decorated with an anti-CD19 recombinant antibody fragment to target malignant B cells, specifically acute lymphoblastic leukemia (ALL) cells. The safety profile and bioavailability of these targeted HSA-nanoparticles were evaluated in vitro and in vivo using a human-zebrafish xenograft model of ALL. The efficacy of the nanostructures in delivering encapsulated doxorubicin and suppressing tumor growth was also assessed.

Results: The HSA coating on polymeric NPs effectively modified the protein corona, preventing opsonization and subsequent macrophage-mediated elimination. The targeted HSA-nanoparticles maintained a safe profile with reduced macrophage interaction and specifically targeted tumor cells in the xenograft model. This resulted in the successful delivery of doxorubicin, tumor growth suppression, and increased survival of the model organisms.

Conclusion: The study demonstrates that HSA-coated nanoparticles can be used as a therapeutic nanoplatform with a safe profile and enhanced bioavailability. The ability to decorate these nanostructures with specific targeting agents, such as anti-CD19 antibodies, opens up the potential for developing versatile therapeutic platforms that can be tailored to target various clinical conditions.

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来源期刊
International Journal of Nanomedicine
International Journal of Nanomedicine NANOSCIENCE & NANOTECHNOLOGY-PHARMACOLOGY & PHARMACY
CiteScore
14.40
自引率
3.80%
发文量
511
审稿时长
1.4 months
期刊介绍: The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area. With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field. Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.
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