A homologous and molecular dual-targeted biomimetic nanocarrier for EGFR-related non-small cell lung cancer therapy

Bin Xu; Fanjun Zeng; Jialong Deng; Lintong Yao; Shengbo Liu; Hengliang Hou; Yucheng Huang; Hongyuan Zhu; Shaowei Wu; Qiaxuan Li; Weijie Zhan; Hongrui Qiu; Huili Wang; Yundong Li; Xianzhu Yang; Ziyang Cao; Yu Zhang; Haiyu Zhou

doi:10.1016/j.bioactmat.2023.04.005

A homologous and molecular dual-targeted biomimetic nanocarrier for EGFR-related non-small cell lung cancer therapy

Bioact Mater. 2023 Apr 19:27:337-347. doi: 10.1016/j.bioactmat.2023.04.005. eCollection 2023 Sep.

Authors

Bin Xu^{1

2}, Fanjun Zeng³, Jialong Deng^{4

1}, Lintong Yao^{1

5}, Shengbo Liu^{6

1}, Hengliang Hou^{4

1}, Yucheng Huang^{7

1}, Hongyuan Zhu¹, Shaowei Wu^{6

1}, Qiaxuan Li^{1

5}, Weijie Zhan^{6

1}, Hongrui Qiu^{8

1}, Huili Wang^{8

1}, Yundong Li⁹, Xianzhu Yang², Ziyang Cao^{10

2}, Yu Zhang¹¹, Haiyu Zhou^{1

6

5

8

4

7}

Affiliations

¹ Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, PR China.
² School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, 511442, PR China.
³ Department of General Practice, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, PR China.
⁴ School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, PR China.
⁵ Shantou University Medical College, Shantou, 515063, PR China.
⁶ The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, PR China.
⁷ School of Medicine, South China University of Technology, Guangzhou, 510006, PR China.
⁸ Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China.
⁹ South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of South China Sea Fishery Resources Exploitation and Utilization, Ministry of Agriculture and Rural Affairs, Guangzhou, 510300, China.
¹⁰ Guangzhou First People's Hospital, South China University of Technology, Guangzhou, 510006, PR China.
¹¹ Department of Orthopedics, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, Guangdong, China.

Abstract

The abnormal activation of epidermal growth factor receptor (EGFR) drives the development of non-small cell lung cancer (NSCLC). The EGFR-targeting tyrosine kinase inhibitor osimertinib is frequently used to clinically treat NSCLC and exhibits marked efficacy in patients with NSCLC who have an EGFR mutation. However, free osimertinib administration exhibits an inadequate response in vivo, with only ∼3% patients demonstrating a complete clinical response. Consequently, we designed a biomimetic nanoparticle (CMNP^@Osi) comprising a polymeric nanoparticle core and tumor cell-derived membrane-coated shell that combines membrane-mediated homologous and molecular targeting for targeted drug delivery, thereby supporting a dual-target strategy for enhancing osimertinib efficacy. After intravenous injection, CMNP^@Osi accumulates at tumor sites and displays enhanced uptake into cancer cells based on homologous targeting. Osimertinib is subsequently released into the cytoplasm, where it suppresses the phosphorylation of upstream EGFR and the downstream AKT signaling pathway and inhibits the proliferation of NSCLC cells. Thus, this dual-targeting strategy using a biomimetic nanocarrier can enhance molecular-targeted drug delivery and improve clinical efficacy.

Keywords: Biomimetic nanoparticles; Clinical efficacy; EGFR mutation; Intracellular drug delivery; Membrane targeting; Non-small cell lung cancer; Tyrosine kinase inhibitor.