Bandyopadhyay Arghya, Yadav Priya, Sarkar Keka, Bhattacharyya Sayan
Department of Chemical Sciences , Centre for Advanced Functional Materials , Indian Institute of Science Education and Research (IISER) , Mohanpur - 741246 , Kolkata , India . Email:
Department of Microbiology , University of Kalyani , Nadia - 741235 , India.
Chem Sci. 2019 May 8;10(24):6184-6192. doi: 10.1039/c9sc00076c. eCollection 2019 Jun 28.
Robust inorganic graphene analogues with atomic level sharp edges have seldom been investigated to decipher the interaction of two-dimensional materials with the cell membrane. Silica nanosheets (NSs) with four different thicknesses between 2.9 nm and 11.1 nm were synthesized by microwave irradiation and these colloidal NSs were able to spontaneously penetrate the cell membrane leaving membrane perforations at their sites of entry. The NS-ingression was most effective with the thinnest NSs, when studied . The atomistic details of the NS-membrane interaction were revealed by molecular dynamics (MD) simulations, which showed that the extraction of phospholipids was most favored when NSs were oriented vertically with respect to the membrane surface. While the folic acid modified NSs demonstrated a riveting tendency to penetrate the cancer cell membrane, co-modification with doxorubicin (DOX) unexpectedly reduced their capability. Migrating away from a conventional drug delivery approach, here we show that silica NSs can kill cancer cells primarily by mechanical scalpelling. Targeted ingress could be achieved through antibody conjugation on the NSs and thus only cancerous HeLa cells are affected by this treatment, leaving the normal HEK-293 cells intact. This destructive ingress through limited oxidative stress offers a previously unexplored route to treat fatal diseases without the necessity of transporting expensive drugs or radiation therapy, thereby bypassing deleterious side effects on healthy cells.
具有原子级锐利边缘的坚固无机石墨烯类似物很少被研究用于解读二维材料与细胞膜的相互作用。通过微波辐射合成了四种不同厚度（2.9纳米至11.1纳米）的二氧化硅纳米片（NSs），这些胶体NSs能够自发穿透细胞膜，并在进入部位留下膜穿孔。研究发现，最薄的NSs的纳米片进入效果最为显著。分子动力学（MD）模拟揭示了NS-膜相互作用的原子细节，结果表明，当NSs相对于膜表面垂直取向时，磷脂的提取最为有利。虽然叶酸修饰的NSs表现出穿透癌细胞膜的铆接倾向，但与阿霉素（DOX）共同修饰却意外地降低了它们的能力。与传统的药物递送方法不同，我们在此表明二氧化硅NSs主要通过机械切割来杀死癌细胞。通过在NSs上进行抗体偶联可以实现靶向进入，因此只有癌细胞系HeLa细胞会受到这种治疗的影响，而正常的HEK-293细胞则保持完整。这种通过有限氧化应激的破坏性进入提供了一条以前未被探索的治疗致命疾病的途径，无需运输昂贵的药物或进行放射治疗，从而避免了对健康细胞的有害副作用。
