Synthetic NRG-1 functionalized DNA nanospindels towards HER2/neu targets for in vitro anti-cancer activity assessment against breast cancer MCF-7 cells
Authors: Wing-Fu Lai
Anam Ahsan
Said Abasse Kassim
Mehreen Jabeen
Muhammad Naveed
Ghulam Jilany Khan
Muhammad Tayyab Ansari
Reyaj Mikrani
Mirza Muhammad Faran Ashraf Baig
Muhammad Asim Farooq
Muhammad Abbas
Journal: Journal of Pharmaceutical and Biomedical Analysis (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: DNA nanospindels (DNA-NS); Daunorubicin (DN); HER2/neu receptor; MCF7 cells; neuregulin-1 (NRG-1) ligand.
Affiliations: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, PR China; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60000, Pakistan. Electronic address: ., Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong Special Administrative Region, PR China; School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, PR China., Department of Pharmaceutics, Basic medicine, and Clinical Pharmacy, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR China., Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60000, Pakistan., School of Pharmacy, Nanjing Medical University, Jiangsu Province, Nanjing 211166, PR China., State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China., College of Animal Science & Veterinary Medicine, Shanxi Agricultural University, Taigu, PR China., Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, PR China., Faculty of Pharmacy, University of Central Punjab, Lahore, 54570, Pakistan.

Abstract:  DNA based nano-carriers synthesized from short circular scaffolds (circular DNA nanotechnology) attains stiffer topology for ligand functionalization (neuregulin-1/NRG-1 ligand) and biological applications (targeted drug delivery). Daunorubicin (DR) is a hydrophobic chemical that requires robust vectors to efficiently encapsulate and avoid its free dispersion in water, biological media and cell culture. Here we design DNA nanospindels (DNA-NS) to efficiently load DR and target the (highly expressed) HER2/neu receptors on the plasma membrane of drug-resistant MCF-7 (breast cancer) cells. DNA-NS were synthesized by polymerizing the DNA-triangles (utilizing 84-nt short circular scaffold strand) into larger DNA nano-ribbons characterized by the native-PAGE testing. AFM results revealed the spinning of DNA nanoribbons on its (own) axis because of the intrinsic curvature of the DNA double helix resulting in the formation of the firm and twisted DNA-NS with the diameter (50-70 nm) and length (0.5-4 μm). DA loading onto DNA-NS was confirmed by the UV shift analysis. The MTT results with the blank DNA-NS evidenced its biocompatibility (remained value of 93%) compared to the decreased viability of the MCF-7 cells after treatment with DNA-NS (DR loaded). These findings were further supported by the analysis of cell proliferation/apoptosis through flow cytometry showing 64% apoptosis after treating with the DR loaded DNA-NS. Hence, through the short circular DNA nanotechnology, we have achieved a stiffer, uniform, and biocompatible DNA-NS for applications in the targeted therapy. 

Retracted: No

PubPeer comments:
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 Same material. Different application. ,