1. Academic Validation
  2. Ligand-installed anti-VEGF genomic nanocarriers for effective gene therapy of primary and metastatic tumors

Ligand-installed anti-VEGF genomic nanocarriers for effective gene therapy of primary and metastatic tumors

  • J Control Release. 2020 Apr 10;320:314-327. doi: 10.1016/j.jconrel.2020.01.026.
Huaping Zhang 1 Jing Liu 1 Qixian Chen 2 Peng Mi 3
Affiliations

Affiliations

  • 1 Department of Radiology, Center for Medical Imaging, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 2 School of Life Science and Biotechnology, Dalian University of Technology, No. 2 Linggong Road, Dalian 116024, China.
  • 3 Department of Radiology, Center for Medical Imaging, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: mi@scu.edu.cn.
Abstract

The systemic dosage regimen exhibited low therapeutic efficacy and incurred severe adverse effect, thus, the development of tumor-targeted therapeutics is crucial important for tumor precision therapy. Herein, the active targeted modulation of tumor microenvironments was schemed by developing hyaluronic acid-installed genomic nanocarriers (HA-NPs) for effectively ablation of both primary and metastatic tumors through anti-vascular endothelial growth factor (anti-VEGF) approach. The anti-VEGF genomic payloads were strategically packaged into the well-defined synthetic nanocarriers by layer-by-layer preparation strategy, exhibiting high colloidal stability and much lower cell viability than the cationic gene carriers. Besides, the HA-NPs could specifically and efficiently internalize with Cancer cells for efficient intracellular gene delivery, leading to high gene transfection efficacy. Moreover, it further demonstrated efficient extravasation, high accumulation and deep penetration in tumors, which markedly facilitated tumor-targeted expression of anti-VEGF genomic payloads for inhabitation of neo-vasculature, consecutively contributing to potent ablation of solid tumors. In addition, the ligand-installed nanocarriers facilitated systemic treatment of melanoma lung metastasis by the expressed anti-VEGF proteins, which were extensively spread along blood circulation and metastatic niches to diminish the formation of neovasculature for tumorigenesis. Therefore, the proposed anti-VEGF genomic nanocarriers could shed intriguing implication in effectively treatment of primary tumors and metastasis.

Keywords

Anti-VEGF; Gene delivery; Layer-by-layer; Metastasis; Nanoparticles; Tumor.

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