Abstract
Cell-penetrating peptides (CPPs) are a promising non-viral vector for gene and drug delivery. CPPs exhibit high cell transfection, and are biocompatible. They can be also conjugated with organic and inorganic nanomaterials, such as magnetic nanoparticles (MNPs), graphene oxide (GO), metal-organic frameworks (MOFs), and chitosan. Nanomaterials offered a high specific surface area and provided relatively straightforward methods to be modified with biomolecules including CPPs and oligonucleotides (ONs). Novel nanomaterials conjugates with CPP/ONs complexes are therefore of interest for cell transfection with high efficiency. In this chapter, we described a summary of the non-viral vectors consisting of CPPs and nanomaterials. The book chapter also included a protocol to generate hybrid biomaterials consisting of CPPs and nanoparticles (NPs) for the delivery of oligonucleotides. The conjugation of NPs with CPPs serves as an effective platform for gene therapy with high cell transfection efficiency. The protocol is simple, offers high cell transfection compared to the CPPs-ONs complexes, and can be used for further improvements using external stimuli.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- CPPs:
-
Cell-penetrating peptides
- GO:
-
Graphene oxide
- HSA:
-
Human serum albumin
- MNPs:
-
Magnetic nanoparticles
- MOFs:
-
Metal-organic frameworks
- mPEG:
-
Methoxy polyethylene glycol
- MRI:
-
Magnetic resonance imaging
- NIR:
-
Near-infrared
- NP:
-
Nanoparticle
- ON:
-
Oligonucleotide
- PEI:
-
Polyethyleneimine
- PFs:
-
PepFects
- PL-PEG:
-
Phospholipid-based amphiphilic polymer
- R8:
-
Octa-arginine
- rGO:
-
Reduced graphene oxide
- SAH:
-
Subarachnoid hemorrhage
- SMAR1:
-
Scaffold matrix attachment region binding protein 1
- TP10:
-
Transportan 10
- ZIFs:
-
Zeolitic imidazolate frameworks
Refernces
Li C, Samulski RJ (2020) Engineering adeno-associated virus vectors for gene therapy. Nat Rev Genet 21:255–272
Wang D, Tai PWL, Gao G (2019) Adeno-associated virus vector as a platform for gene therapy delivery. Nat Rev Drug Discov 18:358–378
Dowaidar M, Regberg J, Dobchev DA, Lehto T, Hällbrink M, Karelson M, Langel Ü (2017) Refinement of a quantitative structure–activity relationship model for prediction of cell-penetrating peptide based transfection systems. Int J Pept Res Ther 23:91–100
Kilk K, El-Andaloussi S, Järver P et al (2005) Evaluation of transportan 10 in PEI mediated plasmid delivery assay. J Control Release 103:511–523
Mäe M, Myrberg H, El-Andaloussi S, Langel Ü (2009) Design of a tumor homing cell-penetrating peptide for drug delivery. Int J Pept Res Ther 15:11–15
Gestin M, Dowaidar M, Langel Ü (2017) Uptake mechanism of cell-penetrating peptides. Adv Exp Med Biol 1030:255–264
Silva S, Almeida AJ, Vale N (2019) Combination of cell-penetrating peptides with nanoparticles for therapeutic application: a review. Biomol Ther 9:22
Abdelhamid HN, Wu H-F (2019) Nanoparticles advance drug delivery for cancer cells. In: Keservani RK, Sharma AK (eds) Nanoparticulate drug delivery systems. Apple Academic Press, New York, pp 121–150
Dowaidar M, Gestin M, Cerrato CP, Jafferali MH, Margus H, Kivistik PA, Ezzat K, Hallberg E, Pooga M, Hällbrink M, Langel Ü (2017) Role of autophagy in cell-penetrating peptide transfection model. Sci Rep 7:12635
Kumaran S, Abdelhamid HN, Hasan N, Wu H-F (2020) Cytotoxicity of palladium nanoparticles against Aspergillus niger. Nanosci Nanotechnol-Asia 10:80–85
Abdelhamid HN (2020) General methods for detection and evaluation of nanotoxicity. In: Nanotoxicity. Elsevier, pp 195–214
Abdelhamid HN (2020) Nanocytotoxicity using matrix-assisted laser desorption ionization mass spectrometry. Future Microbiol 15:385–387
Abdelhamid HN, Wu H-F (2013) Probing the interactions of chitosan capped CdS quantum dots with pathogenic bacteria and their biosensing application. J Mater Chem B 1:6094–6106
Abdelhamid HN, Wu H-F (2015) Proteomics analysis of the mode of antibacterial action of nanoparticles and their interactions with proteins. TrAC Trends Anal Chem 65:30–46
Giodini L, Lo RF, Campagnol D et al (2017) Nanocarriers in cancer clinical practice: a pharmacokinetic issue. Nanomed Nanotechnol Biol Med 13:583–599
Manaia EB, Abuçafy MP, Chiari-Andréo BGBG et al (2017) Physicochemical characterization of drug nanocarriers. Int J Nanomedicine 12:4991–5011
Chen Z-Y, Abdelhamid HN, Wu H-F (2016) Effect of surface capping of quantum dots (CdTe) on proteomics. Rapid Commun Mass Spectrom 30:1403–1412
Shastri L, Abdelhamid HN, Nawaz M, Wu H-F (2015) Synthesis, characterization and bifunctional applications of bidentate silver nanoparticle assisted single drop microextraction as a highly sensitive preconcentrating probe for protein analysis. RSC Adv 5:41595–41603
Abdelhamid HN, Wu H-F (2013) Multifunctional graphene magnetic nanosheet decorated with chitosan for highly sensitive detection of pathogenic bacteria. J Mater Chem B 1:3950–3961
Gopal J, Abdelhamid HN, Hua P-Y, Wu H-F (2013) Chitosan nanomagnets for effective extraction and sensitive mass spectrometric detection of pathogenic bacterial endotoxin from human urine. J Mater Chem B 1:2463
Abdelhamid HN (2018) Nanoparticle assisted laser desorption/ionization mass spectrometry for small molecule analytes. Microchim Acta 185:200
Abdelhamid HN (2017) Organic matrices, ionic liquids, and organic matrices@nanoparticles assisted laser desorption/ionization mass spectrometry. Trends Anal Chem 89:68–98
Abdelhamid HN, Talib A, Wu H-F (2015) Facile synthesis of water soluble silver ferrite (AgFeO2) nanoparticles and their biological application as antibacterial agents. RSC Adv 5:34594–34602
Bhaisare ML, Abdelhamid HN, Wu B-S, Wu H-F (2014) Rapid and direct MALDI-MS identification of pathogenic bacteria from blood using ionic liquid-modified magnetic nanoparticles (Fe3O4@SiO2). J Mater Chem B 2:4671–4683
Abdelhamid HN, Wu H-F (2014) Facile synthesis of nano silver ferrite (AgFeO2) modified with chitosan applied for biothiol separation. Mater Sci Eng C 45:438–445
Abdelhamid HN, Wu HF (2017) Thymine chitosan nanomagnets for specific preconcentration of mercury (II) prior to analysis using SELDI-MS. Microchim Acta 184:1517–1527
Abdelhamid HN (2015) Delafossite nanoparticle as new functional materials: advances in energy, nanomedicine and environmental applications. Mater Sci Forum 832:28–53
Abdelhamid HN (2019) Nanoparticle-based surface assisted laser desorption ionization mass spectrometry: a review. Microchim Acta 186:682
Abdelhamid HN, Lin YC, Wu H-F (2017) Magnetic nanoparticle modified chitosan for surface enhanced laser desorption/ionization mass spectrometry of surfactants. RSC Adv 7:41585–41592
Abdelhamid HN (2016) Laser assisted synthesis, imaging and cancer therapy of magnetic nanoparticles. Mater Focus 5:305–323
Abdelhamid HN (2019) Nanoparticles assisted laser desorption/ionization mass spectrometry. In: Handbook of smart materials in analytical chemistry. Wiley, Chichester, pp 729–755
Laurent S, Forge D, Port M et al (2008) Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem Rev 108:2064–2110
Zhang J, Shin MC, David AE et al (2013) Long-circulating heparin-functionalized magnetic nanoparticles for potential application as a protein drug delivery platform. Mol Pharm 10:3892–3902
Yang HY, Jang M-S, Li Y et al (2017) Multifunctional and redox-responsive self-assembled magnetic nanovectors for protein delivery and dual-modal imaging. ACS Appl Mater Interfaces 9:19184–19192
Yao Q, Bermejo Gómez A, Su J et al (2015) Series of highly stable isoreticular lanthanide metal–organic frameworks with expanding pore size and tunable luminescent properties. Chem Mater 27:5332–5339
Abdelhamid HN, Wu H-F (2015) Synthesis and multifunctional applications of quantum nanobeads for label-free and selective metal chemosensing. RSC Adv 5
Abdelhamid HN, El-Bery HM, Metwally AA et al (2019) Synthesis of CdS-modified chitosan quantum dots for the drug delivery of Sesamol. Carbohydr Polym 214:90–99
Shahnawaz Khan M, Abdelhamid HN, Wu H-F (2015) Near infrared (NIR) laser mediated surface activation of graphene oxide nanoflakes for efficient antibacterial, antifungal and wound healing treatment. Colloids Surf B Biointerfaces 127C:281–291
Abdelhamid HN, Wu H-F (2012) A method to detect metal-drug complexes and their interactions with pathogenic bacteria via graphene nanosheet assist laser desorption/ionization mass spectrometry and biosensors. Anal Chim Acta 751:94–104
Manikandan M, Nasser Abdelhamid H, Talib A, Wu H-F (2014) Facile synthesis of gold nanohexagons on graphene templates in Raman spectroscopy for biosensing cancer and cancer stem cells. Biosens Bioelectron 55:180–186
Nasser Abdelhamid H, Wu B-S, Wu H-F (2014) Graphene coated silica applied for high ionization matrix assisted laser desorption/ionization mass spectrometry: a novel approach for environmental and biomolecule analysis. Talanta 126:27–37
Abdelhamid HN, Wu H-F (2015) Reduced graphene oxide conjugate thymine as a new probe for ultrasensitive and selective fluorometric determination of mercury(II) ions. Microchim Acta 182:1609–1617
Abdelhamid HN, Wu H-F (2014) Ultrasensitive, rapid, and selective detection of mercury using graphene assisted laser desorption/ionization mass spectrometry. J Am Soc Mass Spectrom 25:861–868
Abdelhamid HN, Khan MS, Wu HF (2014) Graphene oxide as a nanocarrier for gramicidin (GOGD) for high antibacterial performance. RSC Adv 4:50035–50046
Wu B-S, Abdelhamid HN, Wu H-F (2014) Synthesis and antibacterial activities of graphene decorated with stannous dioxide. RSC Adv 4:3722
Ashour RM, Abdelhamid HN, Abdel-Magied AF et al (2017) Rare earth ions adsorption onto graphene oxide nanosheets. Solvent Extr Ion Exch 35:91–103
Hua P-Y, Manikandan M, Abdelhamid HN, Wu H-F (2014) Graphene nanoflakes as an efficient ionizing matrix for MALDI-MS based lipidomics of cancer cells and cancer stem cells. J Mater Chem B 2:7334–7343
Hussein KH, Abdelhamid HN, Zou X, Woo H-M (2019) Ultrasonicated graphene oxide enhances bone and skin wound regeneration. Mater Sci Eng C 94:484–492
Abdelhamid HN, Wu H-F (2015) Synthesis of a highly dispersive sinapinic acid@graphene oxide (SA@GO) and its applications as a novel surface assisted laser desorption/ionization mass spectrometry for proteomics and pathogenic bacteria biosensing. Analyst 140:1555–1565
Gopal J, Abdelhamid HN, Huang JH, Wu HF (2016) Nondestructive detection of the freshness of fruits and vegetables using gold and silver nanoparticle mediated graphene enhanced Raman spectroscopy. Sensors Actuators B Chem 224:413–424
Abdelhamid HN, Wu H-F (2019) Graphene and its derivatives as platforms for MALDI-MS. In: Stauber T (ed) Handbook of graphene 2, volume 2: physics, chemistry and biology. Scrivener Publishing, pp 273–290
Zhou X, Laroche F, Lamers GEM et al (2012) Ultra-small graphene oxide functionalized with polyethylenimine (PEI) for very efficient gene delivery in cell and zebrafish embryos. Nano Res 5:703–709
Feng L, Zhang S, Liu Z (2011) Graphene based gene transfection. Nanoscale 3:1252
Yue H, Zhou X, Cheng M, Xing D (2018) Graphene oxide-mediated Cas9/sgRNA delivery for efficient genome editing. Nanoscale 10:1063–1071
Zulfajri M, Abdelhamid HN, Sudewi S et al (2020) Plant part-derived carbon dots for biosensing. Biosensors 10:68. https://doi.org/10.3390/bios10060068
Abdelhamid HN, Talib A, Wu HF (2017) One pot synthesis of gold–carbon dots nanocomposite and its application for cytosensing of metals for cancer cells. Talanta 166:357–363
Abdelhamid HN, Wu H-F (2013) Polymer dots for quantifying the total hydrophobic pathogenic lysates in a single drop. Colloids Surf B Biointerfaces 115C:51–60
Bhagat PN, Jadhav SH, Chattopadhyay S, Paknikar KM (2018) Carbon nanospheres mediated nuclear delivery of SMAR1 protein (DNA binding domain) controls breast tumor in mice model. Nanomedicine 13:353–372
Emam HE, Abdelhamid HN, Abdelhameed RM (2018) Self-cleaned photoluminescent viscose fabric incorporated lanthanide-organic framework (Ln-MOF). Dyes Pigments 159:491–498
Yang Y, Shen K, Lin J et al (2016) A Zn-MOF constructed from electron-rich π-conjugated ligands with an interpenetrated graphene-like net as an efficient nitroaromatic sensor. RSC Adv 6:45475–45481
Zou X, Yao Q, Gómez AB, Su J, Pascanu V, Yun Y, Zheng H, Chen H, Liu L, Abdelhamid HN, Martín-Matute B (2016) A series of highly stable isoreticular lanthanide metal-organic frameworks with tunable luminescence properties solved by rotation electron diffraction and X-ray diffraction. Acta Cryst A A72:136
Abdelhamid HN, Wilk-Kozubek M, El-Zohry AM et al (2019) Luminescence properties of a family of lanthanide metal-organic frameworks. Microporous Mesoporous Mater 279:400–406
Abdelhamid HN (2019) Surfactant assisted synthesis of hierarchical porous metal-organic frameworks nanosheets. Nanotechnology 30:435601
Abdelhamid HN (2020) Zinc hydroxide nitrate nanosheets conversion into hierarchical zeolitic imidazolate frameworks nanocomposite and their application for CO2 sorption. Mater Today Chem 15:100222
Kassem AA, Abdelhamid HN, Fouad DM, Ibrahim SA (2019) Metal-organic frameworks (MOFs) and MOFs-derived CuO@C for hydrogen generation from sodium borohydride. Int J Hydrog Energy 44:31230–31238
Goda MN, Abdelhamid HN, Said AE-AA (2020) Zirconium oxide sulfate-carbon (ZrOSO4@C) derived from carbonized UiO-66 for selective production of dimethyl ether. ACS Appl Mater Interfaces 12:646–653
Abdelhamid HN (2020) Salts induced formation of hierarchical porous ZIF-8 and their applications for CO2 sorption and hydrogen generation via NaBH 4 hydrolysis. Macromol Chem Phys 221:2000031
Abdellah AR, Abdelhamid HN, El-Adasy A-BAAM et al (2020) One-pot synthesis of hierarchical porous covalent organic frameworks and two-dimensional nanomaterials for selective removal of anionic dyes. J Environ Chem Eng 8:104054
Sultan S, Abdelhamid HN, Zou X, Mathew AP (2018) CelloMOF: nanocellulose enabled 3D printing of metal-organic frameworks. Adv Funct Mater 29(2):1805372
Abdelhamid HN, Huang Z, El-Zohry AM et al (2017) A fast and scalable approach for synthesis of hierarchical porous zeolitic imidazolate frameworks and one-pot encapsulation of target molecules. Inorg Chem 56:9139–9146
Abdelhamid HN, Bermejo-Gómez A, Martín-Matute B, Zou X (2017) A water-stable lanthanide metal-organic framework for fluorimetric detection of ferric ions and tryptophan. Microchim Acta 184:3363–3371
Abdelhamid HN, Zou X (2018) Template-free and room temperature synthesis of hierarchical porous zeolitic imidazolate framework nanoparticles and their dye and CO2 sorption. Green Chem 20:1074–1084
Valencia L, Abdelhamid HN (2019) Nanocellulose leaf-like zeolitic imidazolate framework (ZIF-L) foams for selective capture of carbon dioxide. Carbohydr Polym 213:338–345
Abdel-Magied AF, Abdelhamid HN, Ashour RM et al (2019) Hierarchical porous zeolitic imidazolate frameworks nanoparticles for efficient adsorption of rare-earth elements. Microporous Mesoporous Mater 278:175–184
Abdelhamid HN, El-Zohry AM, Cong J et al (2019) Towards implementing hierarchical porous zeolitic imidazolate frameworks in dye-sensitized solar cells. R Soc Open Sci 6:190723
Abdelhamid HN (2020) Hierarchical porous ZIF-8 for hydrogen production via the hydrolysis of sodium borohydride. Dalt Trans 49:4416–4424
Abdelhamid HN (2020) Dye encapsulated hierarchical porous zeolitic imidazolate frameworks for carbon dioxide adsorption. J Environ Chem Eng 8:104008
Kassem AA, Abdelhamid HN, Fouad DM, Ibrahim SA (2020) Hydrogenation reduction of dyes using metal-organic framework-derived CuO@C. Microporous Mesoporous Mater 305:110340
Feng D, Liu T-F, Su J et al (2015) Stable metal-organic frameworks containing single-molecule traps for enzyme encapsulation. Nat Commun 6:5979
Shieh F-K, Wang S-C, Yen C-I et al (2015) Imparting functionality to biocatalysts via embedding enzymes into nanoporous materials by a de novo approach: size-selective sheltering of catalase in metal–organic framework microcrystals. J Am Chem Soc 137:4276–4279
Li P, Moon S-Y, Guelta MA et al (2016) Encapsulation of a nerve agent detoxifying enzyme by a mesoporous zirconium metal–organic framework engenders thermal and long-term stability. J Am Chem Soc 138:8052–8055
Zhang Y, Wang F, Ju E et al (2016) Metal-organic-framework-based vaccine platforms for enhanced systemic immune and memory response. Adv Funct Mater 26:6454–6461
Lian X, Erazo-Oliveras A, Pellois J-P, Zhou H-C (2017) High efficiency and long-term intracellular activity of an enzymatic nanofactory based on metal-organic frameworks. Nat Commun 8:2075
Wang S, Chen Y, Wang S et al (2019) DNA-functionalized metal–organic framework nanoparticles for intracellular delivery of proteins. J Am Chem Soc 141:2215–2219
Yang X, Tang Q, Jiang Y et al (2019) Nanoscale ATP-responsive zeolitic imidazole framework-90 as a general platform for cytosolic protein delivery and genome editing. J Am Chem Soc 141:3782–3786
Abdelhamid HN, Dowaidar M, Hällbrink M, Langel Ü (2020) Gene delivery using cell penetrating peptides-zeolitic imidazolate frameworks. Microporous Mesoporous Mater 300:110173
Dowaidar M, Abdelhamid HN, Hällbrink M et al (2017) Magnetic nanoparticle assisted self-assembly of cell penetrating peptides-oligonucleotides complexes for gene delivery. Sci Rep 7:9159
Dowaidar M, Nasser Abdelhamid H, Hällbrink M et al (2018) Chitosan enhances gene delivery of oligonucleotide complexes with magnetic nanoparticles–cell-penetrating peptide. J Biomater Appl 33:392–401
Dowaidar M, Abdelhamid HN, Hällbrink M et al (2017) Graphene oxide nanosheets in complex with cell penetrating peptides for oligonucleotides delivery. Biochim Biophys Acta 1861:2334–2341
Abdelhamid HN, Dowaidar M, Hällbrink M, Langel Ü (2019) Cell penetrating peptides-hierarchical porous zeolitic imidazolate frameworks nanoparticles: an efficient gene delivery platform. SSRN Electron J 10:2139
Abdelhamid HN, Dowaidar M, Langel Ü (2020) Carbonized chitosan encapsulated hierarchical porous zeolitic imidazolate frameworks nanoparticles for gene delivery. Microporous Mesoporous Mater 302:110200
Acknowledgments
This work was supported by The Swedish Research Council, and Swedish Cancer Foundation, Sweden. H.N. Abdelhamid thanks the Ministry of Higher Education and Scientific Research (MHESR) and Institutional Review Board (IRB) of the Faculty of Science at Assiut University, Egypt for the support.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Dowaidar, M., Abdelhamid, H.N., Langel, Ü. (2022). Improvement of Transfection with PepFects Using Organic and Inorganic Materials. In: Langel, Ü. (eds) Cell Penetrating Peptides. Methods in Molecular Biology, vol 2383. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1752-6_35
Download citation
DOI: https://doi.org/10.1007/978-1-0716-1752-6_35
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-1751-9
Online ISBN: 978-1-0716-1752-6
eBook Packages: Springer Protocols