The increasing importance of sigma-2 receptor as target for the diagnosis and therapy of tumors paves the way for the development of innovative optically traceable fluorescent probes as tumor cell contrast and therapeutic agents. Here, a novel hybrid organic–inorganic nanostructure is developed by combining the superior fluorescent properties of inorganic quantum dots (QDs), coated with a hydrophilic silica shell ([email protected]₂ NPs), the versatility of the silica shell, and the high selectivity for sigma-2 receptor of the two synthetic ligands, namely, the 6-[(6-aminohexyl)oxy]-2-(3-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)propyl)-3,4-dihydroisoquinolin-1(2H)-one (MLP66) and 6-[1-[3-(4-cyclohexylpiperazin-1-yl)propyl]-1,2,3,4-tetrahydronaphthalen-5-yloxy]hexylamine (TA6). The proposed nanostructures represent a challenging alternative to all previously studied organic small fluorescent molecules, based on the same sigma-2 receptor affinity moieties. Flow cytometry and confocal fluorescence microscopy experiments, respectively, on fixed and living cancerous MCF7 cells, which overexpress the sigma-2 receptor, prove the ability of functionalized ([email protected]₂-TA6 and [email protected]₂-MLP66) NPs to be internalized and demonstrate their affinity to the sigma-2 receptor, ultimately validating the targeting properties conveyed to the NPs by sigma-2 ligand conjugation. The presented QD-based nanoprobes possess a great potential as in vitro selective sigma-2 receptor imaging agent and, consequently, could provide a significant impact to future theranostic applications.

中文翻译：

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基于量子点的发光纳米探针用于Sigma-2受体成像

作为肿瘤诊断和治疗靶标的sigma-2受体的重要性与日俱增，为开发创新的光学可追踪荧光探针作为肿瘤细胞对比剂和治疗剂铺平了道路。在这里，结合了无机量子点（QDs）的优异荧光特性，涂有亲水性硅壳（[email protected] ₂ NPs），硅壳的多功能性和较高的合成性，开发了一种新颖的有机-无机杂化纳米结构。两个合成配体，即6-[[（6-氨基己基）氧基] -2-（3-（6,7-二甲氧基-3,4-二氢异喹啉-2（1 H）-丙基）-3,4-二氢异喹啉-1（2 H）-（MLP66）和6- [1- [1-（3-（4-环己基哌嗪-1-基）丙基] -1,2,3,4-四氢萘-5-基氧基]己胺（TA6）。基于相同的sigma-2受体亲和力部分，拟议的纳米结构代表了所有先前研究的有机小荧光分子的具有挑战性的替代方案。流式细胞术和共聚焦荧光显微镜实验分别针对过表达sigma-2受体的固定和活癌MCF7细胞，证明了功能化（[受电子邮件保护] ₂ -TA6和[受电子邮件保护] ₂ -MLP66）NP的能力）被内化并证明它们对sigma-2受体的亲和力，最终验证了通过sigma-2配体结合传递给NP的靶向特性。提出的基于量子点的纳米探针具有巨大的潜力，因为体外选择性sigma-2受体显像剂，因此可能对未来的治疗学应用产生重大影响。