Department of Physics and Nanotechnology, SRM Institute of Science and Technology, Kattankulathur - 603203, Chengalpattu, Tamil Nadu, India; Biomaterials Research Laboratory (BMRL), Department of Chemical Engineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur - 603203, Chengalpattu, Tamil Nadu, India.
Biomaterials Research Laboratory (BMRL), Department of Chemical Engineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur - 603203, Chengalpattu, Tamil Nadu, India.
Int J Pharm. 2024 Oct 25;664:124638. doi: 10.1016/j.ijpharm.2024.124638. Epub 2024 Aug 24.
The fabrications of hollow microcapsules (MCs) with new architecture and ability to incorporate different nanomaterials have received great interest for targeted cancer therapy. Recently, CuS based nanomaterials have been demonstrated to possess the ability to mimic Fenton-like activity in tumor environment and inducing cancer cell apoptosis by generating highly reactive oxygen species (ROS). In this study, we have developed poly(allylamine) hydrochloride (PAH)/dextran sulfate (DS) polyelectrolyte MCs capable of carrying doxorubicin (DOX) for targeted cancer therapy and ultrasound imaging. The electron microscopy investigations showed the formation of polymeric MCs of 3 µm in size with incorporated CuS NRs in their interior structure. The surface modification of MCs with folic acid (FA), and encapsulation of model hydrophilic molecules in MCs was studied by UV-Visible (UV-Vis) spectroscopy, Fourier transform infra-red (FTIR) spectroscopy and confocal laser scanning microscopy. The encapsulation efficiency of DOX was found to be 56 % and the release was found to be linear at pH 5.5 and 7.4 in the absence of ultrasound exposure. The ultrasound exposure resulted in sudden rupture of MCs at 1 MHz and 1 W/cm and caused burst release of DOX at both pH conditions. The FA decorated PAH/DS/CuS NR MCs exhibited improved anti-cancer activity against MDA-MB-231 cancer cells due to the synergistic effects of ultrasound mediated burst release of chemotherapeutic drug (DOX), glutathione-stimulated ROS and targeted cancer therapy. Further, the capsules showed better echogenicity than that of control PAH/DS MCs when imaged under medical ultrasound-scanning system. Hence, the MCs demonstrated in this study have huge potential for targeted cancer theranostics by offering an option to image the cancer cells during the treatment period.
具有新型结构和能够纳入不同纳米材料的中空微胶囊 (MCs) 的制备引起了人们对靶向癌症治疗的极大兴趣。最近，已经证明基于 CuS 的纳米材料具有在肿瘤环境中模拟类 Fenton 活性并通过产生高反应性氧物种 (ROS) 诱导癌细胞凋亡的能力。在这项研究中，我们开发了能够携带多柔比星 (DOX) 进行靶向癌症治疗和超声成像的聚 (烯丙基盐酸盐) (PAH)/葡聚糖硫酸盐 (DS) 聚电解质 MCs。电子显微镜研究表明，形成了 3 µm 大小的聚合物 MCs，其内部结构中掺入了 CuS NRs。通过紫外可见 (UV-Vis) 光谱、傅里叶变换红外 (FTIR) 光谱和共焦激光扫描显微镜研究了 MCs 表面用叶酸 (FA) 修饰和将模型亲水性分子包封在 MCs 中的情况。发现 DOX 的包封效率为 56%，在没有超声暴露的情况下，在 pH 5.5 和 7.4 下，释放呈线性。超声暴露导致 MCs 在 1 MHz 和 1 W/cm 时突然破裂，并在两种 pH 条件下导致 DOX 的爆发释放。由于超声介导的化疗药物 (DOX) 的爆发释放、谷胱甘肽刺激的 ROS 和靶向癌症治疗的协同作用，FA 修饰的 PAH/DS/CuS NR MCs 对 MDA-MB-231 癌细胞表现出增强的抗癌活性。此外，与对照 PAH/DS MCs 相比，当在医学超声扫描系统下成像时，胶囊显示出更好的回声性。因此，本研究中展示的 MCs 具有通过在治疗期间提供对癌细胞进行成像的选择来进行靶向癌症治疗学的巨大潜力。
