Skip to main content

Advertisement

SpringerLink
Log in

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

  • RESEARCH PAPER
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Khan GJ, Sun L, Abbas M, Naveed M, Jamshaid T, Baig MMFA, et al. In-vitro pre-treatment of cancer cells with TGF-B1: A novel approach of Tail vein lung cancer metastasis mouse model for anti-metastatic studies. Curr Mol Pharmacol [Internet]. 2019;12. Available from: http://www.eurekaselect.com/170514/article

  2. Abbas M, Ahmed A, Khan GJ, Baig MMFA, Naveed M, Mikrani R, et al. Clinical evaluation of carcinoembryonic and carbohydrate antigens as cancer biomarkers to monitor palliative chemotherapy in advanced stage gastric cancer. Curr Probl Cancer. 2019:5–17.

  3. Baig MMFA, Shahzad Q, Jabeen M, Saeed HMK, Wahid M, Irfan M, et al. Assessment of compliance in cardiovascular patients in Nishter hospital, Multan, Pakistan Asian J Pharm [Internet] 2015;9:56–9. Available from: http://www.asiapharmaceutics.info/text.asp?2015/9/1/56/150041

  4. Tacar O, Sriamornsak P, Dass CR. Doxorubicin: An update on anticancer molecular action, toxicity and novel drug delivery systems. J. Pharm. Pharmacol. 2013. p. 157–70.

  5. Zhang Q, Jiang Q, Li N, Dai L, Liu Q, Song L, et al. DNA origami as an in vivo drug delivery vehicle for cancer therapy. ACS Nano. 2014;8:6633–43.

    Article  CAS  Google Scholar 

  6. Jiang Q, Song C, Nangreave J, Liu X, Lin L, Qiu D, et al. DNA origami as a carrier for circumvention of drug resistance. J Am Chem Soc. 2012;134:13396–403.

    Article  CAS  Google Scholar 

  7. Khan GJ, Rizwan M, Abbas M, Naveed M, Boyang Y, Naeem MA, et al. Pharmacological effects and potential therapeutic targets of DT-13. Biomed Pharmacother. 2018;97:255–63.

    Article  CAS  Google Scholar 

  8. Zhao YX, Shaw A, Zeng X, Benson E, Nyström AM, Högberg B. DNA origami delivery system for cancer therapy with tunable release properties. ACS Nano [internet]. American Chemical Society. 2012;6:8684–91. Available from. https://doi.org/10.1021/nn3022662.

    Article  CAS  Google Scholar 

  9. Agudelo D, Bourassa P, Bérubé G, Tajmir-Riahi HA. Intercalation of antitumor drug doxorubicin and its analogue by DNA duplex: structural features and biological implications. Int J Biol Macromol 2014

  10. Wang F, Wang YC, Dou S, Xiong MH, Sun TM, Wang J. Doxorubicin-tethered responsive gold nanoparticles facilitate intracellular drug delivery for overcoming multidrug resistance in cancer cells. ACS Nano. 2011;5:3679–92.

    Article  CAS  Google Scholar 

  11. Faran Ashraf Baig MM, Lai W-F, Mikrani R, Jabeen M, Naveed M, Abbas M, et al. Synthetic NRG-1 functionalized DNA nanospindels towards HER2/neu targets for in vitro anti-cancer activity assessment against breast cancer MCF-7 cells. J Pharm Biomed Anal [Internet]. 2020;113133. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0731708519318941

  12. Naveed M, Phil L, Sohail M, Hasnat M, Baig MMFA, Ihsan AU, et al. Chitosan oligosaccharide (COS): an overview. Int J Biol Macromol [Internet] 2019;129:827–43. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0141813018354527

  13. Tikhomirov G, Petersen P, Qian L. Triangular DNA Origami Tilings. J Am Chem Soc. 2018;140:17361–4.

    Article  CAS  Google Scholar 

  14. Ali MM, Li F, Zhang Z, Zhang K, Kang DK, Ankrum JA, et al. Rolling circle amplification: A versatile tool for chemical biology, materials science and medicine. Chem. Soc. Rev. 2014. p. 3324–41.

  15. Baig MMFA, Zhang Q-W, Younis MR, Xia X-H. A DNA nano-device simultaneously activating the EGFR and integrin for enhancing cytoskeletal activity and cancer cell treatment. Nano Lett [Internet] 2019;19:7503–13. Available from: http://pubs.acs.org/doi/10.1021/acs.nanolett.9b03325

  16. Dutta PK, Zhang Y, Blanchard AT, Ge C, Rushdi M, Weiss K, et al. Programmable multivalent DNA-origami tension probes for reporting cellular traction forces. Nano Lett. 2018;18:4803–11.

    Article  CAS  Google Scholar 

  17. Zhao B, O’Brien C, Mudiyanselage APKKK, Li N, Bagheri Y, Wu R, et al. Visualizing intercellular tensile forces by DNA-based membrane molecular probes. J Am Chem Soc. 2017;139:18182–5.

    Article  CAS  Google Scholar 

  18. Gilmour LMR, Macleod KG, McCaig A, Sewell JM, Gullick WJ, Smyth JF, et al. Neuregulin expression, function, and signaling in human ovarian cancer cells. Clin Cancer Res. 2002;8:3933–42.

    CAS  PubMed  Google Scholar 

  19. Liles JS, Arnoletti JP, Kossenkov AV, Mikhaylina A, Frost AR, Kulesza P, et al. Targeting ErbB3-mediated stromal-epithelial interactions in pancreatic ductal adenocarcinoma. Br J Cancer. 2011;105:523–33.

    Article  CAS  Google Scholar 

  20. Baig MMFA, Abbas M, Naveed M, Kassim SA, Khan GJ, Sohail M, et al. Design, synthesis and evaluation of DNA nano-cubes as a core material protected by the alginate coating for oral administration of anti-diabetic drug. J Food Drug Anal [Internet]. Elsevier; 2019 [cited 2019 Apr 26];27:805–14. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1021949819300481

  21. Baig MMFA, Sohail M, Mirjat AA, Naveed M, Majeed F, Raza F, et al. PLL-alginate and the HPMC-EC hybrid coating over the 3D DNA nanocubes as compact nanoparticles for oral administration. Appl Nanosci [Internet]. 2019; Available from: http://link.springer.com/10.1007/s13204-019-01075-5

  22. Muhammad Faran Ashraf Baig M, Naveed M, Abbas M, Chunxia W, Ullah S, Hasnat M, et al. DNA scaffold nanoparticles coated with HPMC/EC for oral delivery. Int J Pharm [Internet]. 2019;562:321–32. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0378517319302467

  23. Baig MMFA, Naveed M, Abbas M, Kassim SA, Khan GJ, Ullah S, et al. Chitosan-coated rectangular DNA nanospheres for better outcomes of anti-diabetic drug. J Nanoparticle Res [Internet]. 2019;21:98. Available from: http://link.springer.com/10.1007/s11051-019-4534-1

  24. Kumar R, El-Sagheer A, Tumpane J, Lincoln P, Wilhelmsson LM, Brown T. Template-directed oligonucleotide strand ligation, covalent intramolecular DNA circularization and catenation using click chemistry. J Am Chem Soc. 2007;129:6859–64.

    Article  CAS  Google Scholar 

  25. Qian P, Seo S, Kim J, Kim S, Lim BS, Liu WK, et al. DNA nanotube formation based on normal mode analysis. Nanotechnology. 2012;23.

  26. Baig MMFA, Khan S, Naeem MA, Khan GJ, Ansari MT. Vildagliptin loaded triangular DNA nanospheres coated with eudragit for oral delivery and better glycemic control in type 2 diabetes mellitus. Biomed Pharmacother. 2018;97:1250–8.

    Article  CAS  Google Scholar 

  27. Li M, Zuo H, Yu J, Zhao X, Mao C. One DNA strand homo-polymerizes into defined nanostructures. Nanoscale. 2017;9:10601–5.

    Article  CAS  Google Scholar 

  28. Sato Y, Endo M, Morita M, Takinoue M, Sugiyama H, Murata S, et al. Environment-dependent self-assembly of DNA origami lattices on phase-separated lipid membranes. Adv Mater Interfaces 2018;5.

  29. Pérez-Ortiz M, Zapata-Urzúa C, Acosta GA, Álvarez-Lueje A, Albericio F, Kogan MJ. Gold nanoparticles as an efficient drug delivery system for GLP-1 peptides. Colloids Surfaces B Biointerfaces. 2017;158:25–32.

    Article  Google Scholar 

  30. Arya P, Pathak K. Assessing the viability of microsponges as gastro retentive drug delivery system of curcumin: optimization and pharmacokinetics. Int J Pharm. 2014;460:1–12.

    Article  CAS  Google Scholar 

  31. Hong F, Jiang S, Lan X, Narayanan RP, Šulc P, Zhang F, et al. Layered-crossover tiles with precisely tunable angles for 2D and 3D DNA crystal engineering. J Am Chem Soc. 2018;140:14670–6.

    Article  CAS  Google Scholar 

  32. Afshan N, Ali M, Wang M, Baig MMFA, Xiao SJ. DNA nanotubes assembled from tensegrity triangle tiles with circular DNA scaffolds. Nanoscale. 2017;9:17181–5.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

All the authors acknowledged State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, China for support.

Author information

Authors and Affiliations

  1. State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, People’s Republic of China

    Mirza Muhammad Faran Ashraf Baig

  2. Faculty of Pharmacy, Bahauddin Zakariya University, Multan, 60000, Pakistan

    Mirza Muhammad Faran Ashraf Baig, Mehreen Jabeen & Muhammad Tayyab Ansari

  3. Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong Special Administrative Region, Hong Kong, People’s Republic of China

    Wing-Fu Lai

  4. School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China

    Wing-Fu Lai

  5. College of Animal Science & Veterinary Medicine, Shanxi Agricultural University, Taigu, People’s Republic of China

    Anam Ahsan

  6. Department of Pharmaceutics, Basic medicine, and Clinical Pharmacy, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, People’s Republic of China

    Muhammad Asim Farooq & Reyaj Mikrani

  7. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, People’s Republic of China

    Muhammad Abbas

  8. School of Pharmacy, Department of Clinical Pharmacology, Nanjing Medical University, Jiangsu Province, Nanjing, 211166, People’s Republic of China

    Muhammad Naveed

  9. Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, People’s Republic of China

    Said Abasse Kassim

  10. School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China

    Faisal Raza

  11. School of Environmental Sciences, Nanjing University, Nanjing, 210023, China

    Afzal Ahmed Dar

Authors
  1. Mirza Muhammad Faran Ashraf Baig
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wing-Fu Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anam Ahsan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mehreen Jabeen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Muhammad Asim Farooq
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Reyaj Mikrani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Muhammad Abbas
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Muhammad Naveed
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Said Abasse Kassim
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Faisal Raza
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Afzal Ahmed Dar
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Muhammad Tayyab Ansari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mirza Muhammad Faran Ashraf Baig.

Ethics declarations

Conflict of Interest

None Declared.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Baig, M.M.F.A., Lai, WF., Ahsan, A. et al. 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. Pharm Res 37, 75 (2020). https://doi.org/10.1007/s11095-020-02803-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11095-020-02803-1

Key Words

Search

Navigation