Key Laboratory of Natural Medicine and Immune Engineering of Henan Province, Henan University, Kaifeng 475004, People's Republic of China.
Int J Nanomedicine. 2020 Apr 23;15:2765-2776. doi: 10.2147/IJN.S244693. eCollection 2020.
Over the past decades, quantum dots (QDs) have shown the broad application in diverse fields, especially in intracellular probing and drug delivery, due to their high fluorescence intensity, long fluorescence lifetime, strong light-resistant bleaching ability, and strong light stability. Therefore, we explore a kind of therapeutic potential against cancer with fluorescent imaging.
In the current study, a new type of QDs (QDs@L-Cys-TAEA-5-FUA) capped with L-cysteine (L-Cys) and tris(2-aminoethyl)amine (TAEA) ligands, and conjugated with 5-fluorouracil-1-acetic acid (5-FUA) has been synthesized. Ligands were characterized by electrospray ionization mass spectrometry and H-nuclear magnetic resonance (H NMR) spectroscopy. The modified QDs were characterized by transmission electron microscopy, ultraviolet and visible spectrophotometry (UV-Vis), and fluorescence microscopy. And the biological activity of modified QDs was explored by using MTT assay with HeLa, SMMC-7721 HepG2, and QSG-7701 cells. The fluorescence imaging of modified QDs was obtained by fluorescence microscope.
The modified QDs are of controllable sizes in the range of 4-5 nm and they possess strong optical emission properties. UV-Vis and fluorescence spectra demonstrated that the L-Cys-TAEA-5-FUA was successfully incorporated into QD nanoparticles. The MTT results demonstrated that L-Cys-TAEA-5-FUA modified QDs could efficiently inhibit the proliferation of cancer cells as compared to the normal cells, illustrating their antitumor efficacy. The mechanistic studies revealed that the effective internalization of modified QDs inside cancer cells could inhibit their proliferation, through excessive production of intracellular reactive oxygen species, leading to apoptosis process.
The present study suggests that modified QDs can enter cells efficiently and could be employed as therapeutic agents for the treatment of various types of cancers with fluorescent imaging.
在过去几十年中，由于量子点（QD）具有高荧光强度、长荧光寿命、强耐光漂白能力和强稳定性，因此在细胞内探测和药物输送等多个领域得到了广泛的应用。因此，我们探索了一种具有荧光成像的抗癌治疗潜力。
在本研究中，合成了一种新型的量子点（QD@L-Cys-TAEA-5-FUA），它由 L-半胱氨酸（L-Cys）和三（2-氨基乙基）胺（TAEA）配体包覆，并与 5-氟尿嘧啶-1-乙酸（5-FUA）连接。通过电喷雾电离质谱和 H 核磁共振（H NMR）光谱对配体进行了表征。通过透射电子显微镜、紫外可见分光光度计（UV-Vis）和荧光显微镜对修饰后的量子点进行了表征。并采用 MTT 法对 HeLa、SMMC-7721 HepG2 和 QSG-7701 细胞进行了修饰量子点的生物活性研究。通过荧光显微镜获得了修饰量子点的荧光成像。
修饰后的量子点尺寸在 4-5nm 范围内可控，具有较强的光学发射性能。UV-Vis 和荧光光谱表明，L-Cys-TAEA-5-FUA 成功地掺入了量子点纳米颗粒中。MTT 结果表明，与正常细胞相比，L-Cys-TAEA-5-FUA 修饰的量子点能够有效地抑制癌细胞的增殖，表明其具有抗肿瘤作用。机制研究表明，修饰后的量子点能够有效地进入癌细胞内部，通过过度产生细胞内活性氧，导致细胞凋亡，从而抑制癌细胞的增殖。
本研究表明，修饰后的量子点可以有效地进入细胞，可作为治疗各种类型癌症的治疗剂，同时具有荧光成像功能。
