Nasri Negar, Saharkhiz Shaghayegh, Dini Ghasem, Ghasemvand Fariba
Department of Biotechnology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, 81746-73441, Iran.
Department of Nanotechnology, Faculty of Chemistry, University of Isfahan, Isfahan, 81746-73441, Iran.
Heliyon. 2024 Sep 2;10(17):e37341. doi: 10.1016/j.heliyon.2024.e37341. eCollection 2024 Sep 15.
In this study, a novel quantum dot (QD)-labeled specific anti-prostate-specific membrane antigen (PSMA) aptamer sequence was conjugated to a pH-responsive niosomal particle platform for delivery of docetaxel (DTX) components. The target cells were overexpressed PSMA. This strategy can minimize the systemic toxicity prevalent in DTX. Synthesis of pH-responsive niosomes was achieved by using thin-film hydration. The conjugation of the aptamer A10 to the niosomal particle was done via a disulfide bond. Furthermore, CdSe/ZnS QDs were fabricated using a hot-injection process, then were functionalized with mercapto propanoic acid (MPA) ligands and attached to the 3' terminal of aptamer via an Amide bind. Moreover, several characterization analyses including dynamic light scattering (DLS), zeta potential, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscope (TEM) were performed. Additionally, 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and apoptosis assays, as well as fluorescence microscopy, were used to assess the performance of the fabricated system. The data revealed a homogenous round-shaped population of niosomes with an average size of 200 nm and a negative surface charge was synthesized successfully. The FTIR and XRD evaluations confirmed the fabrication of both QDs and niosomes and the bioconjugation processes. The drug release happened in a controlled manner with a pH-sensitivity feature. The cellular uptake of aptamer-conjugated particles enhanced and consequently caused more cytotoxicity of prostate cancer cells with overexpression of PSMA. Furthermore, the QDs provided an ability to trace the treatment and its uptake via the targeted tissue. Overall, this study contributed to the development of a low-risk, highly specific platform for the delivery of both therapeutics and imaging agents.
在本研究中，一种新型的量子点（QD）标记的特异性抗前列腺特异性膜抗原（PSMA）适配体序列与一个pH响应性的非离子型脂质体颗粒平台偶联，用于递送多西他赛（DTX）成分。靶细胞为PSMA过表达细胞。该策略可将DTX中普遍存在的全身毒性降至最低。通过薄膜水化法实现了pH响应性非离子型脂质体的合成。适配体A10与脂质体颗粒的偶联通过二硫键完成。此外，采用热注射法制备了CdSe/ZnS量子点，然后用巯基丙酸（MPA）配体进行功能化，并通过酰胺键连接到适配体的3'末端。此外，还进行了多项表征分析，包括动态光散射（DLS）、zeta电位、傅里叶变换红外光谱（FTIR）、X射线衍射（XRD）、扫描电子显微镜（SEM）和透射电子显微镜（TEM）。另外，使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）和细胞凋亡测定以及荧光显微镜来评估所制备系统的性能。数据显示成功合成了平均粒径为200 nm的均匀圆形非离子型脂质体群体，且表面带负电荷。FTIR和XRD评估证实了量子点和非离子型脂质体的制备以及生物偶联过程。药物以具有pH敏感性的可控方式释放。适配体偶联颗粒的细胞摄取增强，从而对PSMA过表达的前列腺癌细胞产生更大的细胞毒性。此外，量子点提供了追踪治疗及其在靶组织中摄取的能力。总体而言，本研究有助于开发一种低风险、高特异性的平台，用于递送治疗剂和成像剂。
