Skip to main content
SpringerLink
Log in

In vitro DNA plasmid condensation and transfection through pH-responsive nanohydrogel

  • Original Research
  • Published:
Progress in Biomaterials Aims and scope Submit manuscript

Abstract

Nanohydrogels (NHs) with the benefits of both nanomaterials and hydrogels unlock novel opportunities and applications in biomedicine. Nowadays, cationic NHs have attracted attention in the delivery of genetic materials into cells. Herein, by using reversible addition-fragmentation chain transfer method, an NH-based poly(hydroxyethyl methacrylate-co-N,N-dimethylaminoethyl methacrylate) and cross-linked by poly(ethylene glycol)diacrylate with pH responsiveness character was developed. Several techniques including nuclear magnetic resonance, Fourier-transform infrared spectroscopy, and gel permeation chromatography confirmed the success in the synthesis. The pH responsiveness of the developed NH was shown by transmission electron microscopy and dynamic light scattering technique. The average sizes of NHs in the normal (7.4) and acidic pH (5.5) were 180 and 390 nm, respectively. The ability of the developed NH to condense genetic materials was checked using gel retardation assay with different ratios of NH and pCMV6-IRES-AcGFP, as a plasmid encoding green fluorescence protein. Results of gel retardation assay showed a decreasing trend in plasmid electrophoretic mobility with the increase in the NH concentration. The NH/plasmid complexes were stopped completely at the ratio of 5 and the plasmid band vanished at the ratio of 10. The quantitative and qualitative results of the cell transfection experiment using different ratios of NH/plasmid showed the ability of NH to carry plasmid molecules into the cancerous cells. The best transfection efficiency was observed by nanohydrogel/plasmid weight ratio of 10, while other ratios including 2, 5 and 20 showed 0.8, 10 and 12% of transfection efficiency, respectively. All the assessed factors showed that NH has the potential to be considered as an efficient gene delivery vehicle.

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

Similar content being viewed by others

Data availability

The raw data generated from analysis of this project are available upon request via correspondence to Dr. Fatemeh Farjadian.

References

  • Ahmadi S, Rabiee N, Bagherzadeh M, Elmi F, Fatahi Y, Farjadian F, Baheiraei N, Nasseri B, Rabiee M, Dastjerd NT (2020) Stimulus-responsive sequential release systems for drug and gene delivery. Nano Today 34:100914

    Article  CAS  Google Scholar 

  • Ahmed M, Narain R (2013) Progress of RAFT based polymers in gene delivery. Prog Polym Sci 38:767–790

    Article  CAS  Google Scholar 

  • Akbarian M, Gholinejad M, Mohammadi-Samani S, Farjadian F (2022) Theranostic mesoporous silica nanoparticles made of multi-nuclear gold or carbon quantum dots particles serving as pH responsive drug delivery system. Micropor Mesopor Mat 329:111512

    Article  CAS  Google Scholar 

  • Akram M, Hussain R (2017) Nanohydrogels: history, development, and applications in drug delivery. Nanocellulose and nanohydrogel matrices: biotechnological and biomedical applications. Wiley, pp 297–330

  • Bhat A, Smith B, Dinu C-Z, Guiseppi-Elie A (2019) Molecular engineering of poly(HEMA-co-PEGMA)-based hydrogels: role of minor AEMA and DMAEMA inclusion. Mater Sci Eng C 98:89–100

    Article  CAS  Google Scholar 

  • Correa S, Grosskopf AK, Lopez Hernandez H, Chan D, Yu AC, Stapleton LM, Appel EA (2021) Translational applications of hydrogels. Chem Rev 121(18):11385–11457

    Article  CAS  Google Scholar 

  • Dalwadi C, Patel G (2015) Application of nanohydrogels in drug delivery systems: recent patents review. Recent Pat Nanotechnol 9(1):17–25

    Article  CAS  Google Scholar 

  • Di J, Gao X, Du Y, Zhang H, Gao J, Zheng A (2020) Size, shape, charge and “stealthy” surface: carrier properties affect the drug circulation time in vivo. Asian J Pharm Sci 16(4):444–458

    Article  Google Scholar 

  • Entezar-Almahdi E, Heidari R, Ghasemi S, Mohammadi-Samani S, Farjadian F (2021) Integrin receptor mediated pH-responsive nano-hydrogel based on histidine-modified poly (aminoethyl methacrylamide) as targeted cisplatin delivery system. J Drug Deliv Sci Technol 62:102402

    Article  CAS  Google Scholar 

  • Fang Z, Wan L-Y, Chu L-Y, Zhang Y-Q, Wu J-F (2015) “Smart” nanoparticles as drug delivery systems for applications in tumor therapy. Expert Opin Drug Deliv 12(12):1943–1953

    Article  CAS  Google Scholar 

  • Farjadian F, Ghasemi A, Gohari O, Roointan A, Karimi M, Hamblin MR (2019a) Nanopharmaceuticals and nanomedicines currently on the market: challenges and opportunities. Nanomedicine 14(1):93–126

    Article  CAS  Google Scholar 

  • Farjadian F, Rezaeifard S, Naeimi M, Ghasemi S, Mohammadi-Samani S, Welland ME, Tayebi L (2019) Temperature and pH-responsive nano-hydrogel drug delivery system based on lysine-modified poly (vinylcaprolactam). Int J Nanomed 14:6901–15

    Article  CAS  Google Scholar 

  • Farjadian F, Roointan A, Mohammadi-Samani S, Hosseini M (2019c) Mesoporous silica nanoparticles: synthesis, pharmaceutical applications, biodistribution, and biosafety assessment. Chem Eng J 359:684–705

    Article  CAS  Google Scholar 

  • Farzanfar J, Farjadian F, Roointan A, Mohammadi-Samani S, Tayebi L (2021) Assessment of pH Responsive delivery of methotrexate based on PHEMA-st-PEG-DA nanohydrogels. Macromol Res 29:54–61

    Article  CAS  Google Scholar 

  • Ghasemiyeh P, Mohammadi-Samani S (2021) Polymers blending as release modulating tool in drug delivery. Front Mater 8:752813. https://doi.org/10.3389/fmats.2021.752813

    Article  Google Scholar 

  • Hendi A, Hassan MU, Elsherif M, Alqattan B, Park S, Yetisen AK, Butt H (2020) Healthcare applications of pH-sensitive hydrogel-based devices: a review. Int J Nanomed 15:3887–3901

    Article  CAS  Google Scholar 

  • Hernandez-Martinez AR (2021) Poly(2-hydroxyethyl methacrylate-co-n, n-dimethylacrylamide)-coated quartz crystal microbalance sensor: membrane characterization and proof of concept. Gels. https://doi.org/10.3390/gels7040151

    Article  Google Scholar 

  • Hernández-Martínez AR, Silva-Cuevas C, Rangel-Miranda D, Lujan-Montelongo JA (2022) Adsorption and swelling studies of 2-hydroxyethyl methacrylate- and N,N-dimethylacrylamide-based porous copolymers and their possible applications for QCM-sensors. Appl Surf Sci. https://doi.org/10.1016/j.apsusc.2021.151508

    Article  Google Scholar 

  • Hosseini M, Farjadian F, Makhlouf ASH (2016) Smart stimuli-responsive nano-sized hosts for drug delivery, industrial applications for intelligent polymers and coatings. Springer, Cham, pp 1–26

    Book  Google Scholar 

  • Kasiński A, Zielińska-Pisklak M, Oledzka E, Sobczak M (2020) Smart hydrogels–synthetic stimuli-responsive antitumor drug release systems. Int J Nanomed 15:4541–4572

    Article  Google Scholar 

  • Kozlovskaya V, Alexander JF, Wang Y, Kuncewicz T, Liu X, Godin B, Kharlampieva E (2014) Internalization of red blood cell-mimicking hydrogel capsules with pH-triggered shape responses. ACS Nano 8:5725–5737

    Article  CAS  Google Scholar 

  • Kroupová J, Horák D, Pacherník J, Dvořák P, Šlouf M (2006) Functional polymer hydrogels for embryonic stem cell support. J Biomed Mater Res B Appl Biomater 76:315–325

    Article  Google Scholar 

  • Lee BK, Yun YH, Park K (2015) Smart nanoparticles for drug delivery: boundaries and opportunities. Chem Eng Sci 125:158–164

    Article  CAS  Google Scholar 

  • Lyle SN, Lourtioz J-M, Lahmani M, Dupas-Haeberlin C, Hesto P (2015) Nanosciences and nanotechnology: evolution or revolution? Springer

  • Ma X, Wang H, Jin S, Wu Y, Liang X-J (2012) Construction of paclitaxel-loaded poly (2-hydroxyethyl methacrylate)-g-poly (lactide)-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine copolymer nanoparticle delivery system and evaluation of its anticancer activity. Int J Nanomed 7:1313–1328

    CAS  Google Scholar 

  • Mantha S, Pillai S, Khayambashi P, Upadhyay A, Zhang Y, Tao O, Pham HM, Tran SD (2019) Smart hydrogels in tissue engineering and regenerative medicine. Materials 12(20):3323

    Article  CAS  Google Scholar 

  • Moeinzadeh S, Jabbari E (2017) Nanoparticles and their applications. Springer handbook of nanotechnology. Springer, pp 335–361

  • Montheard J-P, Chatzopoulos M, Chappard D (1992) 2-hydroxyethyl methacrylate (HEMA): chemical properties and applications in biomedical fields. J Macromol Sci Part C Polym Rev 32:1–34

    Article  Google Scholar 

  • Ni H, Yang Y, Chen Y, Liu J, Zhang L, Wu M (2017) Preparation of a poly(DMAEMA-co-HEMA) self-supporting microfiltration membrane with high anionic permselectivity by electrospinning. e-Polymers 17:149–157

    Article  CAS  Google Scholar 

  • Rizwan M, Yahya R, Hassan A, Yar M, Azzahari AD, Selvanathan V, Sonsudin F, Abouloula CN (2017) pH sensitive hydrogels in drug delivery: brief history, properties, swelling, and release mechanism. Mater Sel Appl Polymer 9(4):137

    Google Scholar 

  • Roointan A, Farzanfar J, Mohammadi-Samani S, Behzad-Behbahani A, Farjadian F (2018) Smart pH responsive drug delivery system based on poly (HEMA-co-DMAEMA) nanohydrogel. Int J Pharm 552:301–311

    Article  CAS  Google Scholar 

  • Rungsardthong U, Deshpande M, Bailey L, Vamvakaki M, Armes SP, Garnett MC, Stolnik S (2001) Copolymers of amine methacrylate with poly (ethylene glycol) as vectors for gene therapy. J Control Release 73:359–380

    Article  CAS  Google Scholar 

  • Samsonova O, Pfeiffer C, Hellmund M, Merkel OM, Kissel T (2011) Low molecular weight pDMAEMA-block-pHEMA block-copolymers synthesized via RAFT-polymerization: potential non-viral gene delivery agents? Polymers 3(2):693–718

    Article  CAS  Google Scholar 

  • Shoukat H, Buksh K, Noreen S, Pervaiz F, Maqbool I (2021) Hydrogels as potential drug-delivery systems: network design and applications. Ther Deliv 12:375–396

    Article  CAS  Google Scholar 

  • Subhan MA, Yalamarty SSK, Filipczak N, Parveen F, Torchilin VP (2021) Recent advances in tumor targeting via EPR effect for cancer treatment. J Pers Med 11(6):571

    Article  Google Scholar 

  • Sun Z, Song C, Wang C, Hu Y, Wu J (2020) Hydrogel-based controlled drug delivery for cancer treatment: a review. Mol Pharm 17:373–391

    CAS  Google Scholar 

  • Tavakoli S, Klar AS (2020) Advanced hydrogels as wound dressings. Biomolecules 10(8):1169

    Article  CAS  Google Scholar 

  • Turner JG, White LR, Estrela P, Leese HS (2021) Hydrogel-forming microneedles: current advancements and future trends. Macromol Biosci 21:1–18. https://doi.org/10.1002/mabi.202000307

    Article  CAS  Google Scholar 

  • Wells CM, Harris M, Choi L, Murali VP, Guerra FD, Jennings JA (2019) Stimuli-responsive drug release from smart polymers. J Funct Biomater 10(3):34

    Article  CAS  Google Scholar 

  • Youngblood RL, Truong NF, Segura T, Shea LD (2018) It’s all in the delivery: designing hydrogels for cell and non-viral gene therapies. Mol Ther 26:2087–2106

    Article  CAS  Google Scholar 

  • Zhang M, Liu Y, Peng J, Liu Y, Liu F, Ma W, Ma L, Yu C-Y, Wei H (2020) Facile construction of stabilized, pH-sensitive micelles based on cyclic statistical copolymers of poly (oligo (ethylene glycol) methyl ether methacrylate-st-N, N-dimethylaminoethyl methacrylate) for in vitro anticancer drug delivery. Polym Chem 11:6139–6148

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by Research Council of Shiraz University of Medical Science under grant No. 1396-01-36-16001 (12959).

Author information

Authors and Affiliations

  1. Pharmaceutical Sciences Research Center, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Fatemeh Farjadian & Soliman Mohammadi-Samani

  2. Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

    Abbas Behzad-Behbahani

  3. Department of Pharmaceutics, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Soliman Mohammadi-Samani

  4. Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran

    Soheila Ghasemi

Authors
  1. Fatemeh Farjadian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abbas Behzad-Behbahani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Soliman Mohammadi-Samani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Soheila Ghasemi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Fatemeh Farjadian or Abbas Behzad-Behbahani.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 301 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Farjadian, F., Behzad-Behbahani, A., Mohammadi-Samani, S. et al. In vitro DNA plasmid condensation and transfection through pH-responsive nanohydrogel. Prog Biomater 11, 219–227 (2022). https://doi.org/10.1007/s40204-022-00187-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40204-022-00187-6

Keywords

Search

Navigation