PO.TB02.01 · 肿瘤生物学

识别纤连蛋白额外结构域 B 的金纳米颗粒作为神经母细胞瘤靶向的创新工具

Fibronectin extra-domain B-recognizing gold nanoparticles as an innovative tool for neuroblastoma targeting

编号 2133 展板 5 时间 4/20 09:00–12:00 区域 Section 28 主讲 Fabio Pastorino, PhD

分会场 In Vivo Imaging

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作者与单位 Authors & Affiliations

Chiara Barisione¹, Silvia Ortona², Veronica Bensa³, Caterina Ivaldo¹, Eleonora Ciampi³, Simonetta Astigiano⁴, Michele Cilli⁴, Luciano Zardi¹, Mirco Ponzoni³, Domenico Palombo⁵, Giovanni Pratesi⁶, Pier Francesco Ferrari⁷, Fabio Pastorino³

¹Department of Surgical and Integrated Diagnostic Sciences, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy,²Department of Experimental Medicine, University of Genoa, Genoa, Italy,³Lab of Experimental Therapies in Oncology, IRCCS Istituto G. Gaslini, Genoa, Italy,⁴Animal Facility, IRCCS Ospedale Policlinico San Martino, Genoa, Italy,⁵Department of Surgical and Integrated Diagnostic Sciences, University of Genoa, Research Center for Biologically Inspired Engineering in Vascular Medicine and Longevity, University of Genoa, Genoa, Italy,⁶Department of Surgical and Integrated Diagnostic Sciences, University of Genoa, Research Center for Biologically Inspired Engineering in Vascular Medicine and Longevity, University of Genoa, Clinic of Vascular and Endovascular Surgery, IRCCS Ospedale Policlinico San Martino, Genoa, Italy,⁷Research Center Biologic Inspired Engineering in Vasc Med and Long, Civil, Chem and Envir Eng UNIGE, IRCCS Ospedale Policlinico San Martino, Genoa, Genoa, Italy

摘要 Abstract

中文摘要

背景/目的：神经母细胞瘤（NB）是儿童最常见的颅外实体瘤，占儿童癌症相关死亡的 12-15%。目前的多模式疗法仍缺乏特异性细胞靶点，导致全身毒性和耐药性。开发创新的肿瘤靶向纳米制剂可能代表一种有前景的方法，可增强 NB 的诊断和抗肿瘤疗效，同时减少脱靶副作用。纤连蛋白额外结构域 B（FN-EDB）在肿瘤微环境中上调。方法：在此，通过免疫组织化学（IHC）染色在多种 NB 动物模型中评估了 FN-EDB 的表达。由 Nano Flow 公司开发了一种用识别 FN-EDB 的抗体（Ab）修饰的金纳米颗粒（L19-AuNP），并通过体外 ELISA 以及在 NB 患者来源异种移植（PDX）模型中通过体内光声成像测试其肿瘤结合能力。结果：所有使用的 NB 模型在肿瘤细胞、基质和肿瘤血管层面均表达 FN-EDB。与非靶向（无 L19 Ab）的 Au-NP（尺寸：35.59 ± 2.54 nm；PDI：0.47 ± 0.08；zeta 电位：-51.18 ± 0.84）相比，L19-AuNP 被发现是稳定的（尺寸：108.70 ± 1.37 nm；PDI：0.29 ± 0.07；zeta 电位：-28.34 ± 0.48），并能在体外特异性结合 FN-EDB。在体内，L19-AuNP 特异性归巢至 NB 的 PDX，并在表达较高水平 FN-EDB 的肿瘤中积累更多。结论：在这项初步研究中，L19-AuNP 被证明是一种特异性结合表达 FN-EDB 的 NB 的新型诊断工具，为开发共包封金部分和 NB 标准治疗药物的诊疗一体化纳米制剂铺平了道路。

查看英文原文 English abstract

Background/Objectives: Neuroblastoma (NB) is the most common extracranial solid tumor in children and accounts for 12-15% of pediatric cancer-related deaths. Current multimodal therapies still lack of specific cellular targets, causing systemic toxicity and drug resistance. The development of innovative tumor-targeted nanoformulations might represent a promising approach to enhance NB diagnosis and antitumor efficacy, while decreasing off targets side effects. Fibronectin extra-domain B (FN-EDB) is upregulated in the tumor microenvironment. Methods: Here, FN-EDB expression was evaluated by immunohistochemical (IHC) staining in several animal models of NB. A gold nanoparticle, decorated with an antibody (Ab) recognizing FN-EDB (L19-AuNP) was developed by the company Nano Flow and its tumor binding was tested by ELISA in vitro and in Patient-Derived Xenografts (PDX) models of NB by photoacoustic imaging in vivo . Results: All models of NB used expressed FN-EDB, at the tumor cell, stroma and tumor vasculature levels. Compared to the non-targeted (no L19 Ab) Au-NP (size: 35.59 ± 2.54 nm; PDI: 0.47 ± 0.08; zeta potential: -51.18 ± 0.84), L19-AuNP was found to be stable (size: 108.70 ± 1.37 nm; PDI: 0.29 ± 0.07; zeta potential: -28.34 ± 0.48) and able to specifically bind to FN-EDB in vitro . In vivo , L19-AuNP specifically homed into PDX of NB, accumulating more in the tumor expressing higher levels of FN-EDB. Conclusions: In this preliminary study, L19-AuNP was shown to be a novel diagnostic tool specific for binding NB expressing FN-EDB, paving the way for the development of theranostic nanoformulations co-encapsulating gold moiety and standard-of-care for NB.

利益披露 Disclosure

C. Barisione, None.. S. Ortona, None.. V. Bensa, None.. C. Ivaldo, None.. E. Ciampi, None.. S. Astigiano, None.. M. Cilli, None.. L. Zardi, None.. M. Ponzoni, None.. D. Palombo, None.. G. Pratesi, None.. P. Ferrari, None.. F. Pastorino, None.

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