Department of Polymer Science & Engineering, College of Chemistry & Chemical Engineering, Nanjing University, Nanjing, 210023, P.R. China.
Chemistry. 2020 Oct 9;26(57):13022-13030. doi: 10.1002/chem.202001480. Epub 2020 Sep 11.
Specifically amplifying the emission signals of optical probes in tumors is an effective way to improve the tumor-imaging sensitivity and contrast. In this paper, the first case of dendron-based fluorescence turn-on probes mediated by a Förster resonance energy transfer (FRET) mechanism is reported. Dendrons up to the fourth generation with a hydrophilic oligo(ethylene glycol) scaffold are synthesized by a solid-phase synthesis strategy, and show precise and defect-free chemical structures. To construct the fluorescence turn-on probe, one Cy5.5 molecule is conjugated to the focal of a G3 dendron through a robust linkage and eight Black Hole Quencher 3 (BHQ-3) molecules are conjugated to its periphery through a PEG chain bearing a reductively cleavable disulfide linkage. By in vitro and in vivo experiments, it is demonstrated that the fluorescence of the dendron-based probe can be activated effectively and rapidly in the reductive environments of tumor cells and tissues, and the probe thus exhibits amplified tumor signals and weak normal tissue signals. Compared with the reported nanoscale turn-on probes, the dendron-based probe has several significant advantages, such as well-defined chemical structure, precisely controllable fluorophore/quencher conjugation sites and ratio, desirable chemical stability, and reproducible pharmacokinetic and pharmacological profiles, and is very promising in tumor detection.
具体来说，增强肿瘤中光学探针的发射信号是提高肿瘤成像灵敏度和对比度的有效方法。本文报道了首例基于树枝状大分子的荧光开启探针，该探针通过Förster 共振能量转移（FRET）机制介导。通过固相合成策略合成了具有亲水性聚（乙二醇）支架的多达第四代树枝状大分子，并且显示出精确且无缺陷的化学结构。为了构建荧光开启探针，将一个 Cy5.5 分子通过强键连接到 G3 树枝状大分子的焦点上，并通过带有可还原断裂二硫键的 PEG 链将八个黑洞淬灭剂 3（BHQ-3）分子连接到其外围。通过体外和体内实验，证明该基于树枝状大分子的探针可以在肿瘤细胞和组织的还原环境中有效地快速激活，并且该探针因此表现出放大的肿瘤信号和较弱的正常组织信号。与报道的纳米级开启探针相比，基于树枝状大分子的探针具有几个显著的优势，例如明确的化学结构、精确可控的荧光团/猝灭剂连接位点和比例、理想的化学稳定性以及可重现的药代动力学和药理学特征，在肿瘤检测中很有前景。
