Polyethylenimine-Functionalized Carbon Dots for Delivery of CRISPR/Cas9 Complexes

Iman Hashemzadeh; Akbar Hasanzadeh; Fatemeh Radmanesh; Beheshteh Khodadadi Chegeni; Elaheh Sadat Hosseini; Jafar Kiani; Ali Shahbazi; Marzieh Naseri; Yousef Fatahi; Helena Nourizadeh; Behjat Kheiri Yeghaneh Azar; Amir R. Aref; Yong Liu; Michael R. Hamblin; Mahdi Karimi

doi:10.1021/acsabm.1c00890

Polyethylenimine-Functionalized Carbon Dots for Delivery of CRISPR/Cas9 Complexes

Iman Hashemzadeh, Akbar Hasanzadeh, Fatemeh Radmanesh, Beheshteh Khodadadi Chegeni, Elaheh Sadat Hosseini, Jafar Kiani, Ali Shahbazi, Marzieh Naseri, Yousef Fatahi, Helena Nourizadeh, Behjat Kheiri Yeghaneh Azar, Amir R. Aref, Yong Liu, Michael R. Hamblin, Mahdi Karimi

Laser Research Centre

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

Abstract

Carbon dots (CDs) have become the focus of many studies due to their outstanding optical properties and good biocompatibility. We investigated their potential application to produce a smart and highly efficient yet nontoxic nanovector for gene delivery. This was achieved by conjugating PEI1.8k-functionalized CDs (synthesized by one-step microwave-assisted pyrolysis) with arginine-disulfide linkers to produce CD-PEI1.8k-Arg nanoparticles. This nanovector could deliver p-CRISPR (9.3 kb) into different types of cell lines with higher efficiency compared to native PEI1.8k or PEI25k. CD-PEI1.8k-Arg also maintained its outstanding transfection efficiency at a high serum concentration and low p-CRISPR dose, compared to PEI25k, which was ineffective under those conditions. Additionally, CD-PEI1.8k-Arg could knock out the GFP gene with great efficiency by delivering the required components of CRISPR/Cas9, including a plasmid encoding Cas9, sgRNA targeting GFP, and Cas9/sgRNA ribonucleoproteins (RNPs) into the HEK 293T-GFP cells. Moreover, the nanoparticles showed potential for the local delivery of p-CRISPR into brain tissue. The remarkable properties of CD-PEI1.8k-Arg could enable the development of a safe, highly efficient gene-delivery nanovector for the treatment of various diseases in the near future.

Original language	English
Pages (from-to)	7979-7992
Number of pages	14
Journal	ACS Applied Bio Materials
Volume	4
Issue number	11
DOIs	https://doi.org/10.1021/acsabm.1c00890
Publication status	Published - 15 Nov 2021

Keywords

CRISPR
brain delivery
carbon dots
gene delivery
smart nanoparticles

ASJC Scopus subject areas

Biomaterials
General Chemistry
Biomedical Engineering
Biochemistry (medical)

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10.1021/acsabm.1c00890

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Hashemzadeh, I., Hasanzadeh, A., Radmanesh, F., Khodadadi Chegeni, B., Hosseini, E. S., Kiani, J., Shahbazi, A., Naseri, M., Fatahi, Y., Nourizadeh, H., Kheiri Yeghaneh Azar, B., Aref, A. R., Liu, Y., Hamblin, M. R., & Karimi, M. (2021). Polyethylenimine-Functionalized Carbon Dots for Delivery of CRISPR/Cas9 Complexes. ACS Applied Bio Materials, 4(11), 7979-7992. https://doi.org/10.1021/acsabm.1c00890

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title = "Polyethylenimine-Functionalized Carbon Dots for Delivery of CRISPR/Cas9 Complexes",

abstract = "Carbon dots (CDs) have become the focus of many studies due to their outstanding optical properties and good biocompatibility. We investigated their potential application to produce a smart and highly efficient yet nontoxic nanovector for gene delivery. This was achieved by conjugating PEI1.8k-functionalized CDs (synthesized by one-step microwave-assisted pyrolysis) with arginine-disulfide linkers to produce CD-PEI1.8k-Arg nanoparticles. This nanovector could deliver p-CRISPR (9.3 kb) into different types of cell lines with higher efficiency compared to native PEI1.8k or PEI25k. CD-PEI1.8k-Arg also maintained its outstanding transfection efficiency at a high serum concentration and low p-CRISPR dose, compared to PEI25k, which was ineffective under those conditions. Additionally, CD-PEI1.8k-Arg could knock out the GFP gene with great efficiency by delivering the required components of CRISPR/Cas9, including a plasmid encoding Cas9, sgRNA targeting GFP, and Cas9/sgRNA ribonucleoproteins (RNPs) into the HEK 293T-GFP cells. Moreover, the nanoparticles showed potential for the local delivery of p-CRISPR into brain tissue. The remarkable properties of CD-PEI1.8k-Arg could enable the development of a safe, highly efficient gene-delivery nanovector for the treatment of various diseases in the near future.",

keywords = "CRISPR, brain delivery, carbon dots, gene delivery, smart nanoparticles",

author = "Iman Hashemzadeh and Akbar Hasanzadeh and Fatemeh Radmanesh and {Khodadadi Chegeni}, Beheshteh and Hosseini, {Elaheh Sadat} and Jafar Kiani and Ali Shahbazi and Marzieh Naseri and Yousef Fatahi and Helena Nourizadeh and {Kheiri Yeghaneh Azar}, Behjat and Aref, {Amir R.} and Yong Liu and Hamblin, {Michael R.} and Mahdi Karimi",

year = "2021",

month = nov,

day = "15",

doi = "10.1021/acsabm.1c00890",

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Hashemzadeh, I, Hasanzadeh, A, Radmanesh, F, Khodadadi Chegeni, B, Hosseini, ES, Kiani, J, Shahbazi, A, Naseri, M, Fatahi, Y, Nourizadeh, H, Kheiri Yeghaneh Azar, B, Aref, AR, Liu, Y, Hamblin, MR & Karimi, M 2021, 'Polyethylenimine-Functionalized Carbon Dots for Delivery of CRISPR/Cas9 Complexes', ACS Applied Bio Materials, vol. 4, no. 11, pp. 7979-7992. https://doi.org/10.1021/acsabm.1c00890

TY - JOUR

T1 - Polyethylenimine-Functionalized Carbon Dots for Delivery of CRISPR/Cas9 Complexes

AU - Hashemzadeh, Iman

AU - Hasanzadeh, Akbar

AU - Radmanesh, Fatemeh

AU - Khodadadi Chegeni, Beheshteh

AU - Hosseini, Elaheh Sadat

AU - Kiani, Jafar

AU - Shahbazi, Ali

AU - Naseri, Marzieh

AU - Fatahi, Yousef

AU - Nourizadeh, Helena

AU - Kheiri Yeghaneh Azar, Behjat

AU - Aref, Amir R.

AU - Liu, Yong

AU - Hamblin, Michael R.

AU - Karimi, Mahdi

PY - 2021/11/15

Y1 - 2021/11/15

N2 - Carbon dots (CDs) have become the focus of many studies due to their outstanding optical properties and good biocompatibility. We investigated their potential application to produce a smart and highly efficient yet nontoxic nanovector for gene delivery. This was achieved by conjugating PEI1.8k-functionalized CDs (synthesized by one-step microwave-assisted pyrolysis) with arginine-disulfide linkers to produce CD-PEI1.8k-Arg nanoparticles. This nanovector could deliver p-CRISPR (9.3 kb) into different types of cell lines with higher efficiency compared to native PEI1.8k or PEI25k. CD-PEI1.8k-Arg also maintained its outstanding transfection efficiency at a high serum concentration and low p-CRISPR dose, compared to PEI25k, which was ineffective under those conditions. Additionally, CD-PEI1.8k-Arg could knock out the GFP gene with great efficiency by delivering the required components of CRISPR/Cas9, including a plasmid encoding Cas9, sgRNA targeting GFP, and Cas9/sgRNA ribonucleoproteins (RNPs) into the HEK 293T-GFP cells. Moreover, the nanoparticles showed potential for the local delivery of p-CRISPR into brain tissue. The remarkable properties of CD-PEI1.8k-Arg could enable the development of a safe, highly efficient gene-delivery nanovector for the treatment of various diseases in the near future.

AB - Carbon dots (CDs) have become the focus of many studies due to their outstanding optical properties and good biocompatibility. We investigated their potential application to produce a smart and highly efficient yet nontoxic nanovector for gene delivery. This was achieved by conjugating PEI1.8k-functionalized CDs (synthesized by one-step microwave-assisted pyrolysis) with arginine-disulfide linkers to produce CD-PEI1.8k-Arg nanoparticles. This nanovector could deliver p-CRISPR (9.3 kb) into different types of cell lines with higher efficiency compared to native PEI1.8k or PEI25k. CD-PEI1.8k-Arg also maintained its outstanding transfection efficiency at a high serum concentration and low p-CRISPR dose, compared to PEI25k, which was ineffective under those conditions. Additionally, CD-PEI1.8k-Arg could knock out the GFP gene with great efficiency by delivering the required components of CRISPR/Cas9, including a plasmid encoding Cas9, sgRNA targeting GFP, and Cas9/sgRNA ribonucleoproteins (RNPs) into the HEK 293T-GFP cells. Moreover, the nanoparticles showed potential for the local delivery of p-CRISPR into brain tissue. The remarkable properties of CD-PEI1.8k-Arg could enable the development of a safe, highly efficient gene-delivery nanovector for the treatment of various diseases in the near future.

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KW - brain delivery

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ER -

Polyethylenimine-Functionalized Carbon Dots for Delivery of CRISPR/Cas9 Complexes

Abstract

Keywords

ASJC Scopus subject areas

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