Multimodality imaging of naturally active melanin nanoparticles targeting somatostatin receptor subtype 2 in human small-cell lung cancer
Multimodality imaging of naturally active melanin nanoparticles targeting somatostatin receptor subtype 2 in human small-cell lung cancer
复制标题
靶向人类小细胞肺癌生长抑素受体亚型 2 的天然活性黑色素纳米颗粒的多模态成像
作者：
Xia Lei;Guo Xiaoyi;Liu Teli;Xu Xiaoxia;Jiang Jinquan;Wang Feng;Cheng Zhen;Zhu Hua;Yang Zhi
生长抑素受体亚型2(SSTR2)在肺神经内分泌肿瘤中高表达，占包括小细胞肺癌(SCLC)在内的所有肺癌的25%。建立小细胞肺癌特异性显像剂用于多模式成像以获得肿瘤完整性信息是可能的。在这里，我们构建了新型多功能有机黑色素纳米颗粒(MNPs)作为载体，并表面负载生长抑素类似物奥曲肽来制备靶向人类小细胞肺癌的纳米探针OCT-PEG-MNPs。MNPs具有良好的光声成像(PAI)功能，可以直接与磁共振造影剂Mn2+络合，N-溴琥珀酰亚胺(NBS)可以作为氧化剂，通过亲电取代反应标记半衰期较长的放射性核素124I。因此，(124I，Mn)OCT-PEGMNPs不仅可以用于PAI，还可以用于正电子发射断层扫描(PET)和磁共振成像(MRI)。建立高表达SSTR2的NCI-H69小细胞肺癌移植瘤模型，评价(124I，Mn)OCT-PEGMNPs的多模式成像能力。该纳米探针在PAI、MRI和PET中表现出良好的成像能力。PA图像显示NCI-H69移植瘤局部光声信号随时间逐渐增强，注射MN-OCT-PEGMNPs后24 h移植瘤T1加权信号强度较扫描前明显增强。MicroPET和生物分布研究表明，注射(124I，Mn)OCT-PEGMNPs 24 h后，NCIH69肿瘤的摄取率(8.03±0.37%ID g−1)显著高于对照组A549模型(3.35±0.54%ID g−1)。这种纳米探针可以考虑用于临床试验，因为它结合了有机纳米颗粒的许多优点。
Somatostatin receptor subtype 2 (SSTR2) is highly expressed in pulmonary neuroendocrine tumors, which account for approximately 25% of all lung cancers including small-cell lung cancer (SCLC). It is possible to establish SCLC-specific imaging agents for multimodal imaging to obtain tumor integrity information. Herein, we constructed novel multifunctional organic melanin nanoparticles (MNPs) as a carrier and surface-loaded somatostatin analog octreotide to produce a human small-cell lung cancer-targeted nanoprobe OCT-PEG-MNPs. MNPs have an excellent photoacoustic imaging (PAI) function and can be directly chelated with the magnetic resonance contrast agent Mn2+, and N-bromo succinimide (NBS) can be used as an oxidant to label the nanoparticles with the long half-life radionuclide 124I by an electrophilic substitution reaction. Therefore, (124I, Mn) OCT-PEG-MNPs can not only be used for PAI but also be used for positron emission tomography (PET) and magnetic resonance imaging (MRI). The NCI-H69 SCLC tumor xenograft model with high SSTR2 expression was constructed to evaluate the multimodal imaging ability of (124I, Mn) OCT-PEG-MNPs. This nanoprobe showed good imaging abilities in PAI, MRI and PET. The PA images showed that the photoacoustic signal in the NCI-H69 tumor site gradually increased with time, and the NCI-H69 xenograft showed a clear increase in the T1-weighted signal intensity after injection of Mn-OCT-PEG-MNPs at 24 h compared to that in the prescan. MicroPET and biodistribution studies showed that the uptake of NCI-H69 tumors (8.03 ± 0.37% ID g−1) was significantly higher than that in the control A549 model (3.35 ± 0.54% ID g−1) after injection of (124I, Mn) OCT-PEG-MNPs at 24 h. The (124I, Mn) OCT-PEG-MNPs were successfully applied to multimodal imaging in a small-cell lung cancer model with high SSTR2 expression. This nanoprobe may be considered for clinical trials since it combines the numerous advantages of organic nanoparticles.