Open Access

Biomaterials

, volume 309 , pages 122573

Polymeric micellar nanoparticles for effective CRISPR/Cas9 genome editing in cancer

Yuzhen Li ¹

Yuzhen Li ^{1, 2}

Chun Li ¹

Chun Li ^{1, 2}

Jiachang Yan ^{1, 2}

Ying Liao ³

Chao Qin ¹

Chengyuan Qin ^{1, 2}

Long Wang ¹

Lingyin Wang ^{1, 2}

Yi Huang ^{1, 2}

Chuan Yang ⁴

Jianwei Wang ³

Xianfeng Ding ⁴

Xin Ding ⁴

Yi-Yan Yang ⁵

Peiyan Yuan ^{1, 2}

Hide authors affiliations Show authors affiliations: 5 affiliations

School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China |

School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China |

State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China |

⁴

School of Medicine, Sun Yat-sen University, Shenzhen, 518107, China |

⁵

Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 30 Biopolis Way, Centros #06-01, Singapore138668, Republic of Singapore |

Publication type: Journal Article

Publication date: 2024-09-01

Elsevier

Biomaterials

scimago Q1

wos Q1

SJR: 2.998

CiteScore: 28.5

Impact factor: 12.9

ISSN: 01429612, 18785905

DOI: 10.1016/j.biomaterials.2024.122573

Copy DOI

PubMed ID: 38677222

Abstract

The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) gene editing has attracted extensive attentions in various fields, however, its clinical application is hindered by the lack of effective and safe delivery system. Herein, we reported a cationic micelle nanoparticle composed of cholesterol-modified branched small molecular PEI (PEI-CHO) and biodegradable PEG-b-polycarbonate block copolymer (PEG-PC), denoted as PEG-PC/PEI-CHO/pCas9, for the CRISPR/Cas9 delivery to realize genomic editing in cancer. Specifically, PEI-CHO condensed pCas9 into nanocomplexes, which were further encapsulated into PEG-PC nanoparticles (PEG-PC/PEI-CHO/pCas9). PEG-PC/PEI-CHO/pCas9 had a PEG shell, protecting DNA from degradation by nucleases. Enhanced cellular uptake of PEG-PC/PEI-CHO/pCas9 nanoparticles was observed as compared to that mediated by Lipo2k/pCas9 nanoparticles, thus leading to significantly elevated transfection efficiency after escaping from endosomes via the proton sponge effect of PEI. In addition, the presence of PEG shell greatly improved biocompatibility, and significantly enhanced the in vivo tumor retention of pCas9 compared to PEI-CHO/pCas9. Notably, apparent downregulation of GFP expression could be achieved both in vitro and in vivo by using PEG-PC/PEI-CHO/pCas9-sgGFP nanoparticles. Furthermore, PEG-PC/PEI-CHO/pCas9-sgMcl1 induced effective apoptosis and tumor suppression in a HeLa tumor xenograft mouse model by downregulating Mcl1 expression. This work may provide an alternative paradigm for the efficient and safe genome editing in cancer.

Found

1 citation

Gaynanova Gulnara

PhD in Chemistry

74 publications, 1 073 citations, 1 review

h-index: 18

A.E. Arbuzov Institute of Organic and Physical Chemistry of the Kazan Scientific Center of the Russian Academy of Sciences

Research interests

Colloidal chemistry

Drug delivery systems

Physical Chemistry

Supramolecular chemistry

Surfactants

1 citation

Vasilyeva Leysan

PhD in Chemistry

29 publications, 492 citations

h-index: 14

A.E. Arbuzov Institute of Organic and Physical Chemistry of the Kazan Scientific Center of the Russian Academy of Sciences

Research interests

Colloidal chemistry

Drug delivery systems

Physical Chemistry

Surfactants

1 citation

Zakharova Lucia

DSc in Chemistry, professor

394 publications, 6 176 citations

h-index: 36

A.E. Arbuzov Institute of Organic and Physical Chemistry of the Kazan Scientific Center of the Russian Academy of Sciences

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GOST |

Cite this

GOST Copy

Li Y. et al. Polymeric micellar nanoparticles for effective CRISPR/Cas9 genome editing in cancer // Biomaterials. 2024. Vol. 309. p. 122573.

GOST all authors (up to 50) Copy

Li Y., Li Y., Li C., Li C., Yan J., Liao Y., Qin C., Qin C., Wang L., Wang L., Huang Y., Yang C., Wang J., Ding X., Ding X., Yang Y., Yuan P. Polymeric micellar nanoparticles for effective CRISPR/Cas9 genome editing in cancer // Biomaterials. 2024. Vol. 309. p. 122573.

RIS |

Cite this

RIS Copy

TY - JOUR

DO - 10.1016/j.biomaterials.2024.122573

UR - https://linkinghub.elsevier.com/retrieve/pii/S0142961224001078

TI - Polymeric micellar nanoparticles for effective CRISPR/Cas9 genome editing in cancer

T2 - Biomaterials

AU - Li, Yuzhen

AU - Li, Chun

AU - Yan, Jiachang

AU - Liao, Ying

AU - Qin, Chao

AU - Qin, Chengyuan

AU - Wang, Long

AU - Wang, Lingyin

AU - Huang, Yi

AU - Yang, Chuan

AU - Wang, Jianwei

AU - Ding, Xianfeng

AU - Ding, Xin

AU - Yang, Yi-Yan

AU - Yuan, Peiyan

PY - 2024

DA - 2024/09/01

PB - Elsevier

SP - 122573

VL - 309

PMID - 38677222

SN - 0142-9612

SN - 1878-5905

ER -

BibTex

Cite this

BibTex (up to 50 authors) Copy

@article{2024_Li,

author = {Yuzhen Li and Yuzhen Li and Chun Li and Chun Li and Jiachang Yan and Ying Liao and Chao Qin and Chengyuan Qin and Long Wang and Lingyin Wang and Yi Huang and Chuan Yang and Jianwei Wang and Xianfeng Ding and Xin Ding and Yi-Yan Yang and Peiyan Yuan},

title = {Polymeric micellar nanoparticles for effective CRISPR/Cas9 genome editing in cancer},

journal = {Biomaterials},

year = {2024},

volume = {309},

publisher = {Elsevier},

month = {sep},

url = {https://linkinghub.elsevier.com/retrieve/pii/S0142961224001078},

pages = {122573},

doi = {10.1016/j.biomaterials.2024.122573}

}

Publisher

Elsevier

Journal

Biomaterials

scimago Q1

wos Q1

SJR

2.998

CiteScore

28.5

Impact factor

12.9

ISSN

01429612 (Print)

18785905 (Electronic)