Theranostic Macromolecules Research Center, School of Chemical Engineering, Sungkyunkwan University , Suwon 16419, Republic of Korea.
Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine and Center for Molecular and Cellular Imaging, Samsung Biomedical Research Institute , Seoul 06351, Republic of Korea.
ACS Appl Mater Interfaces. 2017 Jun 7;9(22):19184-19192. doi: 10.1021/acsami.7b03747. Epub 2017 May 25.
Nanoparticle (NP) based model carriers present an emerging strategy for protein delivery. However, constructing a multifunctional nanocarrier with high loading capacity, diagnostic imaging capacity, and controlled release capability is a tremendous challenge for protein delivery systems. Thus, we herein report on the fabrication of redox-responsive magnetic nanovectors (termed RMNs) through self- assembly of FeO NPs and redox-responsive polymer ligands, which could effectively transport protein and trigger intracellular protein release. These RMNs also exhibited low toxicity, high stability, biocompatibility, and T-weighted contrast-enhancement properties. In addition, they presented a quantized positively charged surface that had the capacity to load cyanine 5.5 (Cy5.5) labeled human serum albumin (HSA) with high loading efficiency (∼84%) via electrostatic interactions and which favored cellular uptake. Notably, studies of the in vitro protein release showed that HSA-Cy5.5-loaded RMNs (RMNs-HSA-Cy5.5) presented minimal cumulative release behavior under physiological conditions but release was rapidly enhanced under high glutathione concentration conditions. Confocal microscopy further revealed that protein was delivered and localized at the perinuclear region of tumor cells. Moreover, the in vivo imaging results confirmed that RMNs-HSA-Cy5.5 could serve as a dual-modal probe for simultaneous near-infrared fluorescence (NIRF) imaging and magnetic resonance (MR) imaging, which can be used for breast cancer diagnosis, and verified higher tumor accumulation of transported protein in a living body. Overall, we believe that these multifunctional RMNs exhibit great promise for protein delivery, cancer diagnosis and therapy, and multimodal imaging, as well as clinical applications.
基于纳米颗粒 (NP) 的模型载体为蛋白质递呈提供了一种新兴策略。然而，构建具有高载药量、诊断成像能力和控制释放能力的多功能纳米载体对于蛋白质递呈系统而言是一个巨大的挑战。因此，我们在此报告了通过 FeO NPs 和氧化还原响应性聚合物配体的自组装制备氧化还原响应性磁性纳米载体 (称为 RMNs)，其可以有效地转运蛋白质并触发细胞内蛋白质释放。这些 RMNs 还表现出低毒性、高稳定性、生物相容性和 T 加权对比增强特性。此外，它们具有量化的正表面电荷，能够通过静电相互作用高效负载 Cy5.5 标记的人血清白蛋白 (HSA)（载药量约为 84%），并有利于细胞摄取。值得注意的是，体外蛋白质释放研究表明，HSA-Cy5.5 负载的 RMNs (RMNs-HSA-Cy5.5) 在生理条件下表现出最小的累积释放行为，但在高谷胱甘肽浓度条件下释放迅速增强。共聚焦显微镜进一步显示蛋白质被递送到肿瘤细胞的核周区域并定位于此。此外，体内成像结果证实 RMNs-HSA-Cy5.5 可用作同时近红外荧光 (NIRF) 成像和磁共振 (MR) 成像的双模态探针，可用于乳腺癌诊断，并证实了在体内转运蛋白质的更高肿瘤积累。总的来说，我们相信这些多功能 RMNs 在蛋白质递呈、癌症诊断和治疗以及多模态成像以及临床应用方面具有广阔的应用前景。
