2. Academic Validation
  3. Delivery of an ERK inhibitor using bioactive lipid nanoparticles reduces angiogenesis and prevents oral squamous cell carcinoma development

Delivery of an ERK inhibitor using bioactive lipid nanoparticles reduces angiogenesis and prevents oral squamous cell carcinoma development

  • J Nanobiotechnology. 2025 Jul 18;23(1):524. doi: 10.1186/s12951-025-03577-7.
Zixian Huang # 1 2 3,  Junyue Fang # 1 2 4,  Li Lin # 1 2 5,  Nvlue Cai # 6,  Siyu Chen 6,  Gui He 1 2 4,  Yuan Cao 1 2,  Guo Wu 1 2,  Yuepeng Wang 1 2 3,  Wende Li 7,  Zhiquan Huang 8 9 10,  Phei Er Saw 11 12 13
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, P. R. China.
  • 2 Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-Sen Memorial Hospital, Foshan, 528200, P. R. China.
  • 3 Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, P. R. China.
  • 4 Cellular and Molecular Diagnostics Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, P. R. China.
  • 5 Department of Dermatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, P. R. China.
  • 6 Guangdong Provincial Lab Animal Monitoring Center, Guangdong Provincial Biotechnology Research Institute, Guangzhou, 510663, P. R. China.
  • 7 Guangdong Provincial Lab Animal Monitoring Center, Guangdong Provincial Biotechnology Research Institute, Guangzhou, 510663, P. R. China. gdmcli@qq.com.
  • 8 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, P. R. China. hzhquan@mail.sysu.edu.cn.
  • 9 Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-Sen Memorial Hospital, Foshan, 528200, P. R. China. hzhquan@mail.sysu.edu.cn.
  • 10 Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, P. R. China. hzhquan@mail.sysu.edu.cn.
  • 11 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, P. R. China. caipeie@mail.sysu.edu.cn.
  • 12 Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-Sen Memorial Hospital, Foshan, 528200, P. R. China. caipeie@mail.sysu.edu.cn.
  • 13 Department of General Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat- Sen University, Guangzhou, 510120, P. R. China. caipeie@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 40682120 DOI: 10.1186/s12951-025-03577-7
Abstract

Extracellular regulated protein kinases (ERK) signaling is aberrantly activated in oral squamous cell carcinoma (OSCC), and targeting ERK signaling with ERK1/2 inhibitors is a potential strategy for OSCC treatment. However, methods for the more efficient delivery of ERK inhibitors to improve drug utilization remains a pressing challenge. Notably, the application of antiangiogenic therapies to treat OSCC has received increasing attention, yet single therapies often have very limited efficacy. The combination of antiangiogenic therapies with strategies targeting ERK1/2 signaling for the treatment of OSCC is very promising. In this study, we utilized bioactive Phospholipids (dipalmitoyl phosphatidic acid, DPPA) with antiangiogenic functions to encapsulate a small-molecule ERK Inhibitor (called NP-AE) and constructed an intrinsically biotherapeutically active nanomedicine delivery platform with dual therapeutic efficacy. NP-AE effectively inhibited the proliferation and promoted the Apoptosis of OSCC cell lines. A tongue orthotopic xenograft model and a patient-derived xenograft (PDX) model of OSCC were subsequently used to investigate its therapeutic effect. The nanoplatform was able to accumulate in tumor tissues and was internalized by tumor cells after intravenous administration. NP-AE effectively inhibited ERK1/2 phosphorylation and Angptl2 and VEGFA expression in OSCC in vitro and in vivo and significantly inhibited the growth of xenografts. Taken together, these findings suggest that targeting ERK1/2 signaling in combination with antiangiogenic therapy by NP-AE may be a promising strategy for the treatment of OSCC.

Keywords

Antiangiogenic; Dipalmitoyl phosphatidic acid (DPPA); ERK1/2 inhibitor; Nanoparticles; Oral squamous cell carcinoma (OSCC).

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-111407
    98.13%, ERK1/2 Inhibitor
    ERK