Synthesis of Ligand Functionalized ErbB-3 Targeted Novel DNA Nano-Threads Loaded with the Low Dose of Doxorubicin for Efficient In Vitro Evaluation of the Resistant Anti-Cancer Activity
Authors: Wing-Fu Lai
Anam Ahsan
Said Abasse Kassim
Mehreen Jabeen
Muhammad Naveed
Faisal Raza
Muhammad Tayyab Ansari
Afzal Ahmed Dar
Reyaj Mikrani
Mirza Muhammad Faran Ashraf Baig
Muhammad Asim Farooq
Muhammad Abbas
Journal: Pharmaceutical Research (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: DNA nano-threads (DNA-NTs); Doxorubicin (Dox); ErbB3 receptors; Neuregulin-1 (NRG1); resistant cancer.
Affiliations: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, People's Republic of China. ., Faculty of Pharmacy, Bahauddin Zakariya University, Multan, 60000, Pakistan. ., Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong Special Administrative Region, Hong Kong, People's Republic of China., School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, People's Republic of China., College of Animal Science & Veterinary Medicine, Shanxi Agricultural University, Taigu, People's Republic of China., Faculty of Pharmacy, Bahauddin Zakariya University, Multan, 60000, Pakistan., Department of Pharmaceutics, Basic medicine, and Clinical Pharmacy, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, People's Republic of China., State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, People's Republic of China., School of Pharmacy, Department of Clinical Pharmacology, Nanjing Medical University, Jiangsu Province, Nanjing, 211166, People's Republic of China., Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, People's Republic of China., School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China., School of Environmental Sciences, Nanjing University, Nanjing, 210023, China.

Abstract:  Purpose: Doxorubicin (Dox) being a hydrophobic drug needs a unique carrier for the effective encapsulation with uniformity in the aqueous dispersion, cell culture media and the biological-fluids that may efficiently target its release at the tumor site. Methods: Circular DNA-nanotechnology was employed to synthesize DNA Nano-threads (DNA-NTs) by polymerization of triangular DNA-tiles. It involved circularizing a linear single-stranded scaffold strand to make sturdier and rigid triangles. DNA-NTs were characterized by the AFM and Native-PAGE tests. Dox binding and loading to the Neuregulin1 (NRG1) functionalized DNA based nano-threads (NF-DBNs) was estimated by the UV-shift analysis. The biocompatibility of the blank NRG-1/DNA-NTs and enhanced cytotoxicity of the NF-DBNs was assessed by the MTT assay. Cell proliferation/apoptosis was analyzed through the Flow-cytometry experiment. Cell-surface binding and the cell-internalization of the NF-DBNs was captured by the double-photon confocal microscopy (DPCM). Results: The AFM images revealed uniform DNA-NTs with the diameter 30 to 80 nm and length 400 to 800 nm. PAGE native gel was used for the further confirmation of the successful assembly of the strands to synthesize DNA-NTs that gave one sharp band with the decreased electrophoretic mobility down the gel. MTT assay showed that blank DNA-NTs were biocompatible to the cells with less cytotoxicity even at elevated concentrations with most of the cells (94%) remaining alive compared to the dose-dependent enhanced cytotoxicity of NF-DBNs further evidenced by the Flow-cytometry analysis. Conclusion: Uniform and stiffer DNA-NTs for the potential applications in targeted drug delivery was achieved through circular DNA scaffolding. 

Retracted: No

PubPeer comments:
 *[right]* Fig 4b,  PAGE gel analysis . *[left]* Fig 4A from [Abbas et al (2020)] . ![] Other appearances of that protean molecular ladder: ![] Fig 4A from [Baig et al (2019)] : ![] ,