Mann Garima, Chauhan Kanchan, Adhikari Anupriya, Juarez-Moreno Karla, Kumar Nikhil, Daksh Shivani, Thirumal Meganathan, Datta Anupama
Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Delhi, India.
Department of Chemistry, University of Delhi, Delhi, India.
Drug Dev Res. 2025 Aug;86(5):e70138. doi: 10.1002/ddr.70138.
Mesoporous silica nanoparticles have been extensively utilized for targeted drug delivery; the drugs are encapsulated in the pores, while the surface can be modified to make the nanoparticles target-specific. The work presented here focuses on the development of multifunctional theranostic mesoporous silica nanoparticles with estrogen receptor-positive [ER(+)] breast cancer as the target. The surface of the nanoparticles was dually functionalized to make the nanoparticles target-specific using an estradiol derivative via a facile click reaction and to attach a Tc complexing agent (DTPA) for SPECT imaging. The size of the spherical nanoparticles was 80-110 nm, and the nanosystem was subjected to various physicochemical analysis techniques. Mesoporous nanoparticles were loaded with tamoxifen, an FDA-approved ER antagonist. Drug release at pH 5.8 was much more rapid than at physiological pH 7.4, a beneficial characteristic for controlled drug delivery at the tumor site. Cellular internalization and competitive binding studies indicated estradiol-mediated preferential uptake by MCF-7 cells. The nanocarrier exhibited good antiproliferative activity towards the ER(+) MCF 7 cells with a 92% decline in cellular viability in 48 h, whereas the cellular viability of the estrogen receptor-negative [ER(-)] MDA-MB-231 cells remained > 60%. Thus, our results suggest a high theranostic potential of MSN-Est for breast cancer management.
介孔二氧化硅纳米粒子已被广泛用于靶向药物递送；药物被封装在孔中，而其表面可被修饰以使纳米粒子具有靶向特异性。本文介绍的工作重点是开发以雌激素受体阳性[ER(+)]乳腺癌为靶点的多功能诊疗介孔二氧化硅纳米粒子。通过简便的点击反应，使用雌二醇衍生物对纳米粒子表面进行双重功能化，使其具有靶向特异性，并连接用于单光子发射计算机断层扫描（SPECT）成像的锝络合剂（二乙三胺五乙酸，DTPA）。球形纳米粒子的尺寸为80 - 110纳米，该纳米系统经过了各种物理化学分析技术的检测。介孔纳米粒子装载了他莫昔芬，一种美国食品药品监督管理局（FDA）批准的雌激素受体拮抗剂。在pH 5.8时的药物释放比在生理pH 7.4时快得多，这对于在肿瘤部位进行可控药物递送是一个有利特性。细胞内化和竞争性结合研究表明，雌二醇介导MCF - 7细胞优先摄取。该纳米载体对ER(+) MCF 7细胞表现出良好的抗增殖活性，48小时内细胞活力下降92%，而雌激素受体阴性[ER(-)] MDA - MB - 231细胞的细胞活力仍> 60%。因此，我们的结果表明介孔二氧化硅-雌激素纳米粒子（MSN-Est）在乳腺癌治疗方面具有很高的诊疗潜力。
