International Journal of Nanomedicine (Nov 2022)

HA-DOPE-Modified Honokiol-Loaded Liposomes Targeted Therapy for Osteosarcoma

  • Zhang X,
  • Chen H,
  • Zhang Y,
  • Huang Q,
  • Feng J,
  • Xing H,
  • Fu X,
  • Yan X,
  • Zhang Y,
  • Xu Q,
  • Liang J

Journal volume & issue
Vol. Volume 17
pp. 5137 – 5151

Abstract

Read online

Xiangxiang Zhang, Huaen Chen, Yang Zhang, Qijing Huang, Jianjia Feng, Haoyu Xing, Xiaguo Fu, Xiufang Yan, Yingying Zhang, Qin Xu, Jianming Liang Artemisinin Research Center, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of ChinaCorrespondence: Jianming Liang, Artemisinin Research Center, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China, Email [email protected]: Osteosarcoma (OS) is the most common bone cancer with a high risk of metastasis, high growth rate, and poor prognosis. Honokiol (HNK) is a general ingredient of traditional Chinese medicine, with a potential anti-tumor effect. However, HNK is insoluble in water and lacks drug targeting, which limits its clinical application. To improve the OS therapeutic effect of HNK, we used HNK-loaded liposomes modified with hyaluronic acid-phospholipid conjugates (HA-DOPE) to treat OS based on the HA interaction with CD44.Methods: The HNK-loaded liposomes were prepared via thin-film hydration and sonication. HA-DOPE was used to combine the HNK-loaded liposomes (HA-DOPE@Lips/HNK) via sonication and co-extrusion. HA-DOPE@Lips/HNK were characterized with respect to size, zeta potential, polymer dispersity index (PDI), and stability, and transmission electron microscopy was performed. Cellular uptake, cell viability, cell apoptosis, cell cycle, and mitochondrial activity were utilized to evaluate the antitumor effect in vitro. The biodistribution, xenograft tumor growth inhibition, and safety of HA-DOPE@Lips/HNK were evaluated in 143B OS xenograft mice in vivo.Results: The particle size, PDI, and zeta potential of HA-DOPE@Lips/HNK were 146.20± 0.26 nm, 0.20± 0.01, and − 38.45± 0.98 mV, respectively. The encapsulation rate and drug loading were 80.14± 0.32% and 3.78± 0.09%, respectively. HA-DOPE@Lips/HNK could inhibit cell proliferation, cause apoptosis, block the cell cycle and disrupt mitochondrial activity. HA-DOPE@Lips/HNK specially delivered the drug into the tumor and inhibited tumor growth, and showed no obvious toxicity to normal tissues.Conclusion: HA-DOPE@Lips/HNK could deliver HNK into the tumor site and had a good antitumor ability in vitro and in vivo. In addition, HA-DOPE@Lips/HNK increased the antitumor effects of HNK. Thus, it provides a promising nanocarrier to improve drug delivery in OS therapy.Keywords: honokiol, liposomes, osteosarcoma, hyaluronic acid

Keywords