CRISPR-Cas9 Cancer Gene Editing Graphene Quantum Dots In Vitro

Journal

Advanced functional materials
ISSN: 1616-301X
Titre abrégé: Adv Funct Mater
Pays: Germany
ID NLM: 101190390

Informations de publication

Date de publication:
23 Nov 2023
Historique:
pmc-release: 23 11 2024
medline: 25 12 2023
pubmed: 25 12 2023
entrez: 25 12 2023
Statut: ppublish

Résumé

CRISPR-Cas9 is a programmable gene editing tool with a promising potential for cancer gene therapy. This therapeutic function is enabled in the present work via the non-covalent delivery of CRISPR ribonucleic protein (RNP) by cationic glucosamine/PEI-derived graphene quantum dots (PEI-GQD) that aid in overcoming physiological barriers and tracking genes of interest. PEI-GQD/RNP complex targeting the TP53 mutation overexpressed in ~50% of cancers successfully produces its double-stranded breaks in solution and in PC3 prostate cancer cells. Restoring this cancer "suicide" gene can promote cellular repair pathways and lead to cancer cell apoptosis. Its repair to the healthy form performed by simultaneous PEI-GQD delivery of CRISPR RNP and a gene repair template leads to a successful therapeutic outcome: 40% apoptotic cancer cell death, while having no effect on non-cancerous HeK293 cells. The translocation of PEI-GQD/RNP complex into PC3 cell cytoplasm is tracked via GQD intrinsic fluorescence, while EGFP-tagged RNP is detected in the cell nucleus, showing the successful detachment of the gene editing tool upon internalization. Using GQDs as non-viral delivery and imaging agents for CRISPR-Cas9 RNP sets the stage for image-guided cancer-specific gene therapy.

Identifiants

pubmed: 38144446
doi: 10.1002/adfm.202305506
pmc: PMC10746168
pii:
doi:

Types de publication

Journal Article

Langues

eng

Déclaration de conflit d'intérêts

Conflict of Interest The authors declare no conflict of interest.

Auteurs

Bong Lee (B)

Department of Physics and Astronomy, Texas Christian University, Fort Worth, TX.

Klara Gries (K)

Department of Chemistry and Biochemistry, Heidelberg University, Heidelberg, Germany.

Alina R Valimukhametova (AR)

Department of Physics and Astronomy, Texas Christian University, Fort Worth, TX.

Ryan L McKinney (RL)

Department of Physics and Astronomy, Texas Christian University, Fort Worth, TX.

Roberto Gonzalez-Rodriguez (R)

Department of Physics, University of North Texas, Denton, TX.

Ugur C Topkiran (UC)

Department of Physics and Astronomy, Texas Christian University, Fort Worth, TX.

Jeffery Coffer (J)

Department of Chemistry and Biochemistry, Texas Christian University, Fort Worth, TX.

Giridhar R Akkaraju (GR)

Department of Biology, Texas Christian University, Fort Worth, TX.

Anton V Naumov (AV)

Department of Physics and Astronomy, Texas Christian University, Fort Worth, TX.

Classifications MeSH