A DNA-based nanocarrier for efficient cancer therapy

The study aimed to achieve enhanced targeted cytotoxicity and cell-internalization of cisplatin-loaded deoxyribonucleic acid-nanothread (CPT-DNA-NT), mediated by scavenger receptors into HeLa cells. DNA-NT was developed with stiff-topology utilizing circular-scaffold to encapsulate CPT. Atomic force...

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Bibliographic Details
Published in:Journal of pharmaceutical analysis 2021-06, Vol.11 (3), p.330-339
Main Authors: Abbas, Muhammad, Baig, Mirza Muhammad Faran Ashraf, Zhang, Yaliang, Yang, Yu-Shun, Wu, Songyu, Hu, Yiqiao, Wang, Zhong-Chang, Zhu, Hai-Liang
Format: Article
Language:English
Subjects:
Apoptosis
Atomic force microscopy
Biocompatibility
Cancer
Cancer therapies
Caveolae
Cell viability
Cisplatin
Cytotoxicity
Deoxyribonucleic acid
DNA
DNA-nanothread
Drug delivery
Drug delivery systems
Endocytosis
Flow cytometry
Gel electrophoresis
HeLa cell line
Internalization
Nanoparticles
Original
Polyacrylamide
Scavenger receptors
Toxicity
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Summary:The study aimed to achieve enhanced targeted cytotoxicity and cell-internalization of cisplatin-loaded deoxyribonucleic acid-nanothread (CPT-DNA-NT), mediated by scavenger receptors into HeLa cells. DNA-NT was developed with stiff-topology utilizing circular-scaffold to encapsulate CPT. Atomic force microscopy (AFM) characterization of the DNA-NT showed uniformity in the structure with a diameter of 50-150 nm and length of 300-600 nm. The successful fabrication of the DNA-NT was confirmed through native-polyacrylamide gel electrophoresis analysis, as large the molecular-weight (polymeric) DNA-NT did not split into constituting strands under applied current and voltage. The results of cell viability confirmed that blank DNA-NT had the least cytotoxicity at the highest concentration (512 nM) with a viability of 92% as evidence of its biocompatibility for drug delivery. MTT assay showed superior cytotoxicity of CPT-DNA-NT than that of the free CPT due to the depot release of CPT after DNA-NT internalization. The DNA-NT exhibited targeted cell internalizations with the controlled intracellular release of CPT (from DNA-NT), as illustrated in confocal images. Therefore, in vitro cytotoxicity assessment through flow cytometry showed enhanced apoptosis (72.7%) with CPT-DNA-NT (compared to free CPT; 64.4%). CPT-DNA-NT, being poly-anionic, showed enhanced endocytosis via scavenger receptors.
ISSN:2095-1779
2214-0883
2214-0883
DOI:10.1016/j.jpha.2020.03.005