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一种靶向生存素用于胰腺癌诊断的金纳米笼探针。

A Gold Nanocage Probe Targeting Survivin for the Diagnosis of Pancreatic Cancer.

作者信息

Song Lina, Ren Shuai, Yue Yali, Tian Ying, Wang Zhongqiu

机构信息

Department of Radiology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.

出版信息

Pharmaceutics. 2023 May 19;15(5):1547. doi: 10.3390/pharmaceutics15051547.

Abstract

In this paper, Au nanocages (AuNCs) loaded with the MRI contrast agent gadolinium (Gd) and capped with the tumor-targeting gene survivin (Sur-AuNC•Gd-Cy7 nanoprobes) were designed and applied as a targeted imaging agent for pancreatic cancer. With its capacity to transport fluorescent dyes and MR imaging agents, the gold cage is an outstanding platform. Furthermore, it has the potential to transport different drugs in the future, making it a unique carrier platform. The utilization of Sur-AuNC•Gd-Cy7 nanoprobes has proven to be an effective means of targeting and localizing survivin-positive BxPC-3 cells within their cytoplasm. By targeting survivin, an antiapoptotic gene, the Sur-AuNC•Gd-Cy7 nanoprobe was able to induce pro-apoptotic effects in BxPC-3 pancreatic cancer cells. The biocompatibility of AuNCs•Gd, AuNCs•Gd-Cy7 nanoparticles, and Sur-AuNC•Gd-Cy7 nanoprobes is evaluated through the hemolysis rate assay. The stability of AuNCs•Gd, AuNCs•Gd-Cy7 nanoparticles, and Sur-AuNC•Gd-Cy7 nanoprobes was evaluated by determining their hydrodynamic dimensions following storage in different pH solutions for a corresponding duration. Excellent biocompatibility and stability of the Sur-AuNC•Gd-Cy7 nanoprobes will facilitate their further utilization in vivo and in vitro. The surface-bound survivin plays a role in facilitating the Sur-AuNC•Gd-Cy7 nanoprobes' ability to locate the BxPC-3 tumor. The probe was modified to incorporate Gd and Cy7, thereby enabling the simultaneous utilization of magnetic resonance imaging (MRI) and fluorescence imaging (FI) techniques. In vivo, the Sur-AuNC•Gd-Cy7 nanoprobes were found to effectively target and localize survivin-positive BxPC-3 tumors through the use of MRI and FI. After being injected via the caudal vein, the Sur-AuNC•Gd-Cy7 nanoprobes were found to accumulate effectively in an in situ pancreatic cancer model within 24 h. Furthermore, these nanoprobes were observed to be eliminated from the body through the kidneys within 72 h after a single injection. This characteristic is crucial for a diagnostic agent. Based on the aforementioned outcomes, the Sur-AuNC•Gd-Cy7 nanoprobes have significant potential advantages for the theranostic treatment of pancreatic cancer. This nanoprobe possesses distinctive characteristics, such as advanced imaging abilities and specific drug delivery, which offer the possibility of enhancing the precision of diagnosis and efficacy of treatment for this destructive illness.

摘要

在本文中,设计了负载有磁共振成像(MRI)造影剂钆(Gd)并以肿瘤靶向基因生存素(Sur-AuNC•Gd-Cy7纳米探针)封端的金纳米笼(AuNCs),并将其用作胰腺癌的靶向成像剂。金笼具有运输荧光染料和MR成像剂的能力,是一个出色的平台。此外,它未来还有运输不同药物的潜力,使其成为一个独特的载体平台。事实证明,利用Sur-AuNC•Gd-Cy7纳米探针是在其细胞质内靶向和定位生存素阳性BxPC-3细胞的有效手段。通过靶向抗凋亡基因生存素,Sur-AuNC•Gd-Cy7纳米探针能够在BxPC-3胰腺癌细胞中诱导促凋亡作用。通过溶血率测定评估了AuNCs•Gd、AuNCs•Gd-Cy7纳米颗粒和Sur-AuNC•Gd-Cy7纳米探针的生物相容性。通过在不同pH溶液中储存相应时间后测定其流体动力学尺寸,评估了AuNCs•Gd、AuNCs•Gd-Cy7纳米颗粒和Sur-AuNC•Gd-Cy7纳米探针的稳定性。Sur-AuNC•Gd-Cy7纳米探针优异的生物相容性和稳定性将促进其在体内和体外的进一步应用。表面结合的生存素在促进Sur-AuNC•Gd-Cy7纳米探针定位BxPC-3肿瘤的能力方面发挥作用。该探针经过修饰以掺入Gd和Cy7,从而能够同时利用磁共振成像(MRI)和荧光成像(FI)技术。在体内,通过MRI和FI发现Sur-AuNC•Gd-Cy7纳米探针能够有效靶向和定位生存素阳性BxPC-3肿瘤。经尾静脉注射后,发现Sur-AuNC•Gd-Cy7纳米探针在24小时内有效地在原位胰腺癌模型中蓄积。此外,单次注射后72小时内观察到这些纳米探针通过肾脏从体内清除。这一特性对于诊断剂至关重要。基于上述结果,Sur-AuNC•Gd-Cy7纳米探针在胰腺癌的诊疗中具有显著的潜在优势。这种纳米探针具有独特的特性,如先进的成像能力和特异性药物递送,为提高这种破坏性疾病的诊断精度和治疗效果提供了可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d165/10221143/60025094c28c/pharmaceutics-15-01547-sch001.jpg

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