Dipsacus Asperoides-Derived Exosomes-Like Nanoparticles Inhibit the Progression of Osteosarcoma via Activating P38/JNK Signaling Pathway

Int J Nanomedicine. 2024 Feb 2:19:1097-1108. doi: 10.2147/IJN.S446594. eCollection 2024.

Abstract

Introduction: Osteosarcoma is a prevalent and highly malignant primary bone tumor. However, current clinical therapeutic drugs for osteosarcoma are not suitable for long-term use due to significant side effects. Therefore, there is an urgent need to develop new drugs with fewer side effects. Dipsacus asperoides C. Y. Cheng et T. M. Ai, a traditional Chinese medicine, is commonly used for its anti-inflammatory, anti-pain, bone fracture healing, and anti-tumor effects. In this study, we investigated the effects of exosome-like nanoparticles derived from Dipsacus asperoides (DAELNs) on osteosarcoma cells in vitro and in vivo.

Methods: DAELNs were isolated and purified from Dipsacus asperoides and their physical and chemical properties were characterized using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The cellular uptake of DAELNs in osteosarcoma cells was analyzed by PKH26 staining. The proliferation, invasion, migration, and apoptosis of osteosarcoma cells were assessed using CCK8 assay, EdU assay, colony-formation assay, transwell assay, wound healing assay, and mitochondrial membrane potential measurement, respectively. The regulatory mechanism of DAELNs inhibiting the progression of osteosarcoma via activating P38/JNK signaling pathway was investigated using Western blotting and immunohistochemistry. Moreover, the therapeutic effects of DAELNs were evaluated using in vivo small animal imaging assay, HE staining, and immunohistochemistry.

Results: Our results showed that DAELNs inhibited the proliferation, invasion, migration, and fostered the apoptosis of osteosarcoma cells in vitro and suppressed the tumor growth of osteosarcoma cells in a xenograft nude mouse model. Furthermore, the bio-distribution of DiD-labeled DAELNs showed preferential targeting of osteosarcoma tumors and excellent biosafety in histological analysis of the liver and kidney. Mechanistically, DAELNs activated the P38/JNK signaling pathway-induced apoptosis.

Conclusion: Taken together, DAELNs are novel, natural, and osteosarcoma-targeted agents that can serve as safe and effective therapeutic approaches for the treatment of osteosarcoma.

Keywords: Dipsacus asperoides-derived exosomes-like nanoparticles; P38/JNK signaling pathway; osteosarcoma.

MeSH terms

  • Animals
  • Apoptosis
  • Bone Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Dipsacaceae* / chemistry
  • Disease Models, Animal
  • Exosomes* / metabolism
  • Humans
  • MAP Kinase Signaling System
  • Mice
  • Osteosarcoma* / pathology

Grants and funding

This research was funded by the Guangdong and Enterprises Joint Fund of Public Health and Medicine Area, China (2022A1515220054), Science and Technology Program of Zhanjiang, China (2021A05069), Special Fund for Affiliated Hospital of Guangdong Medical University “Clinical Medicine +” CnTech Co-construction Platform (CLP2021A001), Discipline Construction Project of Guangdong Medical University (4SG23281G), China Post-doctoral Science Foundation (2022M710847), Postdoctoral Science Foundation of the Affiliated Hospital of Guangdong Medical University(1037Z20220053), Open Funding of Affiliated Hospital of Guangdong Medical University-research of autophagy and diseases.