GAP-43靶向吲哚菁绿负载近红外荧光探针在体内实时定位胰腺癌神经周围浸润病变

IF 4.7 4区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Nanomedicine: Nanotechnology, Biology and Medicine Pub Date : 2023-06-01 DOI:10.1016/j.nano.2023.102671
Wen Liang Lu MD , Houfang Kuang MD , Jianyou Gu MD , Xiaojun Hu MD , Bo Chen PhD , Yingfang Fan PhD
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引用次数: 0

摘要

目的胰腺癌的神经周围浸润(PNI)与局部复发、远处转移和预后不良有关。然而,很少有人尝试在术中识别PNI。为了方便肿瘤的精确R0切除,我们计划开发一种以GAP-43为靶点,吲哚菁绿(ICG)为载体的PNI术中成像荧光探针。方法采用肽抗体结合ICG构建探针。利用PC12与肿瘤细胞共培养模型建立体外神经侵袭模型和小鼠坐骨神经侵袭模型,在体外和体内验证其靶向性。小动物成像系统和手术导航系统证实了探针的潜在临床适用性。建立了坐骨神经损伤模型,验证了探针的靶向性。结果我们使用胰腺癌样本和公共数据库确认GAP-43在胰腺癌中优先过表达,特别是在PNI中。与肿瘤细胞共培养后,PC12细胞表现出较高的GAP-43RA-PEG-ICG探针特异性吸收。在坐骨神经侵袭实验中,探针组动物在PNI处的荧光信号明显强于ICG-NP和对侧正常神经组。虽然只有60%的小鼠在肉眼看来有R0切除,但小动物成像系统和手术荧光导航系统可以以R0精度切除肿瘤。探针成像实验试验中使用的损伤模型表明,无论损伤是肿瘤浸润还是物理损伤,探针都能特异性靶向损伤神经。结论我们开发了一种活性靶向近红外荧光(NIRF)探针GAP-43Ra-ICG-PEG,可特异性结合体外PNI模型中gap -43阳性神经细胞。该探针在临床前模型中有效地显示了胰腺癌的PNI病变,为nif引导的胰腺手术开辟了新的可能性,特别是对PNI患者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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GAP-43 targeted indocyanine green-loaded near-infrared fluorescent probe for real-time mapping of perineural invasion lesions in pancreatic cancer in vivo

Objective

Perineural invasion (PNI) is associated with local recurrence, distant metastasis, and a poor prognosis in pancreatic cancer. However, rare attempt was made to identified the PNI intraoperative. To facilitate precise R0 excision of the tumor, we planned to develop a fluorescent probe for intraoperative imaging of the PNI using GAP-43 as the target and indocyanine green (ICG) as the carrier.

Methods

The probe was created by binding peptide antibody and ICG. Its targeting was tested in vitro and in vivo using a co-culture model of PC12 and tumor cells to create an in vitro neural invasion model and a mouse sciatic nerve invasion model. The small animal imaging system and surgical navigation system confirmed the probe's potential clinical applicability. The sciatic nerve damage model was created to confirm the probe's targeting.

Results

We used the pancreatic cancer samples and the public database to confirm that GAP-43 was preferentially overexpressed in pancreatic cancer, particularly in PNI. PC12 cells showed high GAP-43RA-PEG-ICG probe-specific absorption after being co-cultured with tumor cells in vitro. In the sciatic nerve invasion experiment, animals in probe group displayed a significantly stronger fluorescence signal at the PNI compared to ICG-NP and the contralateral normal nerves groups. Although only 60 % of mice appeared to have R0 resections by the naked eye, small animal imaging systems and surgical fluorescence navigation systems could remove the tumor with R0 precision. The injury model used in the probe imaging experimental trials demonstrated that the probe was specifically targeted to the injured nerve, regardless of whether the injury was infiltrated by a tumor or physical.

Conclusion

We developed the GAP-43Ra-ICG-PEG, an active-targeting near-infrared fluorescent (NIRF) probe, that specifically binds to GAP-43-positive neural cells in an in vitro model of PNI. The probe efficiently visualized PNI lesions in pancreatic cancer in preclinical models, opening up new possibilities for NIRF-guided pancreatic surgery, particularly for PNI patients.

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来源期刊
CiteScore
8.10
自引率
3.60%
发文量
104
审稿时长
4.6 months
期刊介绍: Nanomedicine: Nanotechnology, Biology and Medicine (NBM) is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
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