A Recombinant Targeted Bionanoparticle In Vitro Expressing a Gene-Editing Protein for Epidermal Growth Factor Receptor Mutant Lung Cancer

  • ACS Nano. 2026 Feb 17;20(6):4920-4941. doi: 10.1021/acsnano.5c17709.
Yuxin Ren  1  2 ,  Jiarui Xu  1  2 ,  Qian Luo  1  2 ,  Peishan Li  1  2 ,  Min Jiang  1  2 ,  Yuntao Cheng  1  2 ,  Hongrui Zhang  1  2 ,  Dingyi Wei  1  2 ,  Wenjing Bai  1  2 ,  Sunan Liu  1  2 ,  Guiling Wang  1  2 ,  Ying Xie  1  2 ,  Jianwei Li  1  2 ,  Wanliang Lu  1  2
Affiliations
  • 1. State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Advanced Pharmaceutical Preparation, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
  • 2. PKU Medicine-Zhendong Pharmaceutical Joint Laboratory of Advanced Preparation, Health Science Center, Peking University, Beijing 100191, China.
PMID: 41645678 DOI: 10.1021/acsnano.5c17709
Abstract

Epidermal growth factor receptor (EGFR) mutation is a significant driving factor in the occurrence and progression of lung Cancer. How to effectively block the abnormal expression of EGFR remains a key issue that urgently needs to be addressed, as it is of vital importance for the effective treatment of this Cancer. Here, we report a recombinant targeted bionanoparticle that in vitro expresses Cas9 protein (tBioNP vitro-Cas9) for gene editing of EGFR mutant lung Cancer. The nanoparticle was developed by transfection of four plasmids (Gag-Cas9, Gag, sgRNA, VSV-G Azi) into 293T cells to form a type of bionanoparticle and modifying it with a targeted polymer material (DBCO-PEG-FA), and it showed a cancer-targeted property, faster Cancer cellular uptake, higher gene editing efficiency with lower off-target effects, and therapy efficacy in mice, indicating a translational prospect. In conclusion, the study provides a recombinant bionanoparticle in vitro expressing a Cas9 gene editing system and offers a potential strategy for gene therapy of EGFR mutant lung Cancer.

Keywords
EGFR; gene editing; in vitro expressing Cas9; lung cancer; recombinant bionanoparticle.
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