Journal article
Liposomes Containing Zinc-Based Chemotherapeutic Drug Block Proliferation and Trigger Apoptosis in Breast Cancer Cells
ACS applied bio materials, Vol.6(12), pp.5310-5323
12/18/2023
DOI: 10.1021/acsabm.3c00587
PMID: 37988654
Abstract
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)(2)Zn and (L2)(2)Zn, which are characterized by standard analytical and spectroscopic methods. (L2)(2)Zn, but not (L1)(2)Zn 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)(2)Zn and Lip-(L2)(2)Zn 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)(2)Zn and Lip-(L2)(2)Zn 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.
Details
- Title: Subtitle
- Liposomes Containing Zinc-Based Chemotherapeutic Drug Block Proliferation and Trigger Apoptosis in Breast Cancer Cells
- Creators
- Mallayasamy Siva - SRM Institute of Science and TechnologyKiran Das - Centre of Biomedical ResearchSubhabrata Guha - Chittaranjan National Cancer InstituteSubramaniyam Sivagnanam - SRM Institute of Science and TechnologyGaurav Das - Chittaranjan National Cancer InstituteAbhijit Saha - SRM Institute of Science and TechnologyAdele Stewart - Florida Atlantic UniversityBiswanath Maity - Centre of Biomedical ResearchPriyadip Das - SRM Institute of Science and Technology
- Resource Type
- Journal article
- Publication Details
- ACS applied bio materials, Vol.6(12), pp.5310-5323
- Publisher
- Amer Chemical Soc
- DOI
- 10.1021/acsabm.3c00587
- PMID
- 37988654
- ISSN
- 2576-6422
- eISSN
- 2576-6422
- Number of pages
- 14
- Grant note
- Council of Scientific and Industrial Research (CSIR) India; Council of Scientific & Industrial Research (CSIR) - India 01/3077/21/EMR-II / Council of Scientific and Industrial Research, India; Council of Scientific & Industrial Research (CSIR) - India ICMR 5/4/1-22/CVD/2022 NCD-I / Department of Biotechnology (DBT); Department of Biotechnology (DBT) India DST/INSPIRE/04/2020/001299 / Indian Council of Medical Research; Indian Council of Medical Research (ICMR) NCCS, Pune DST-INSPIRE Project
- Language
- English
- Date published
- 12/18/2023
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984618647602771
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