RGD-functionalised melanin nanoparticles for intraoperative photoacoustic imaging-guided breast cancer surgery.

RGD-functionalised melanin nanoparticles for intraoperative photoacoustic imaging-guided breast cancer surgery.
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RGD 功能化黑色素纳米颗粒用于术中光声成像引导乳腺癌手术。

DOI:
10.1007/s00259-021-05545-3
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发表时间:
2022-03
影响因子:
9.1
通讯作者:
Zhang GJ
Zhang GJ
中科院分区:
医学1区
文献类型:
--
作者:
Liu JJ;Wang Z;Nie LM;Zhu YY;Li G;Lin LL;Chen M;Zhang GJ

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获得无肿瘤边缘对于避免再次切除和减少保乳手术后局部复发至关重要;然而,它仍然具有挑战性。影像引导手术可精确检测残留病变并辅助手术切除。本文中,我们描述了与环Arg-Gly-Asp(cRGD)肽缀合的水溶性黑色素纳米颗粒(MNP)用于乳腺癌光声成像(派)和手术导航。合成cRGD-MNP并表征其形态、光声特性和稳定性。通过使用乳腺癌细胞、MDA-MB-231荷瘤小鼠或FVB/N-Tg(MMTV-PyVT)634 Mul/J小鼠模型来确定cRGD-MNP的肿瘤靶向和毒性。派用于在MDA-MB-231荷瘤小鼠中定位肿瘤并指导手术切除。cRGD-MNP表现出优异的体外和体内肿瘤靶向,具有低毒性。对MDA-MB-231荷瘤小鼠静脉给药cRGD-MNP显示,2 h时光声(PA)强度增强约2.1倍,肿瘤部位PA强度与周围正常组织PA强度的比值为3.2 ± 0.1,高于使用MNP时的比值(1.7 ± 0.3)。类似地,在MMTV-PyVT转基因小鼠中注射cRGD-MNP后2小时,自发性乳腺癌中的PA信号增加约2.5倍。术前派评估肿瘤体积,并提供三维(3D)重建图像,以准确制定手术计划。实时派后的手术切除显示与组织病理学分析高度一致。这些结果强调了cRGD-MNP介导的派为乳腺癌成像和精确肿瘤切除提供了强大的工具。具有良好PA性质的cRGD-MNP具有巨大的临床转化潜力。在线版本包含补充材料,可通过10.1007/s 00259 -021-05545-3获得。
Obtaining tumour-free margins is critical for avoiding re-excision and reducing local recurrence following breast-conserving surgery; however, it remains challenging. Imaging-guided surgery provides precise detection of residual lesions and assists surgical resection. Herein, we described water-soluble melanin nanoparticles (MNPs) conjugated with cyclic Arg-Gly-Asp (cRGD) peptides for breast cancer photoacoustic imaging (PAI) and surgical navigation. The cRGD-MNPs were synthesised and characterized for morphology, photoacoustic characteristics and stability. Tumour targeting and toxicity of cRGD-MNPs were determined by using either breast cancer cells, MDA-MB-231 tumour-bearing mice or the FVB/N-Tg (MMTV-PyVT) 634Mul/J mice model. PAI was used to locate the tumour and guide surgical resection in MDA-MB-231 tumour-bearing mice. The cRGD-MNPs exhibited excellent in vitro and in vivo tumour targeting with low toxicity. Intravenous administration of cRGD-MNPs to MDA-MB-231 tumour-bearing mice showed an approximately 2.1-fold enhancement in photoacoustic (PA) intensity at 2 h, and the ratio of the PA intensity at the tumour site to that in the surrounding normal tissue was 3.2 ± 0.1, which was higher than that using MNPs (1.7 ± 0.3). Similarly, the PA signal in the spontaneous breast cancer increased ~ 2.5-fold at 2 h post-injection of cRGD-MNPs in MMTV-PyVT transgenic mice. Preoperative PAI assessed tumour volume and offered three-dimensional (3D) reconstruction images for accurate surgical planning. Surgical resection following real-time PAI showed high consistency with histopathological analysis. These results highlight that cRGD-MNP-mediated PAI provide a powerful tool for breast cancer imaging and precise tumour resection. cRGD-MNPs with fine PA properties have great potential for clinical translation. The online version contains supplementary material available at 10.1007/s00259-021-05545-3.
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