化学
细胞凋亡
癌细胞
脂质体
癌症研究
细胞生长
细胞周期
癌症
生物物理学
生物化学
生物
医学
内科学
作者
Mallayasamy Siva,Kiran Das,Subhabrata Guha,Subramaniyam Sivagnanam,Gaurav Das,Abhijit Saha,Adele Stewart,Biswanath Maity,Priyadip Das
出处
期刊:ACS applied bio materials
[American Chemical Society]
日期:2023-11-21
卷期号:6 (12): 5310-5323
被引量:3
标识
DOI:10.1021/acsabm.3c00587
摘要
Platinum-based chemotherapeutic drugs are effective in killing malignant cells but often trigger drug resistance or off-target side effects. Unlike platinum, zinc is used as an endogenous cofactor for several cellular enzymes and may, thus, display increased biocompatibility. In this present study, we have rationally designed and synthesized two substituted phenanthro[9,10-d]imidazole-based ligands L1 and L2 with pyridine and quinoline substitution at the 2 position and their corresponding Zn(II) complexes; (L1)2Zn and (L2)2Zn, which are characterized by standard analytical and spectroscopic methods. (L2)2Zn, but not (L1)2Zn has intrinsic fluorescence, indicating its potential utility in imaging applications. To facilitate cellular uptake, we generated liposomal formations with a phospholipid DMPC (1,2-Dimyristoyl-sn-glycero-3-phosphocholine) through molecular self-assembly. These liposomal formulations Lip-(L1)2Zn and Lip-(L2)2Zn were able to enter breast cancer cells, induce DNA fragmentation, arrest the cell cycle at the G0/G1 phase, decrease proliferation, and promote apoptosis by activating the DNA damage response. Importantly, both Lip-(L1)2Zn and Lip-(L2)2Zn decreased the size of breast cancer cell-based spheroids, indicating they may be capable of suppressing tumor growth. Our work represents an important proof-of-concept exercise demonstrating that successful liposomal formation of phenanthro[9,10-d]imidazole-based Zn(II) complexes with inherent optical properties have great promise for the development of imaging probes and efficient anticancer drugs.
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