Inhibition of growth and metastasis of breast cancer by targeted delivery of 17-hydroxy-jolkinolide B via hyaluronic acid-coated liposomes

Dan Liu; Qi Zhang; Jing Wang; Shuang Guan; Defu Cai; Jicheng Liu

doi:10.1016/j.carbpol.2020.117572

Inhibition of growth and metastasis of breast cancer by targeted delivery of 17-hydroxy-jolkinolide B via hyaluronic acid-coated liposomes

Carbohydr Polym. 2021 Apr 1:257:117572. doi: 10.1016/j.carbpol.2020.117572. Epub 2021 Jan 5.

Authors

Dan Liu¹, Qi Zhang², Jing Wang³, Shuang Guan⁴, Defu Cai⁵, Jicheng Liu⁶

Affiliations

¹ Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China. Electronic address: liudan@qmu.edu.cn.
² Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China. Electronic address: zhangqi@qmu.edu.cn.
³ Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China. Electronic address: wangjing@qmu.edu.cn.
⁴ Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China. Electronic address: Guans@qmu.edu.cn.
⁵ Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China. Electronic address: cai@qmu.edu.cn.
⁶ Institute of Medicine and Drug Research, Qiqihar Medical University, Qiqihar, PR China. Electronic address: Jcliu@qmu.edu.cn.

PMID: 33541631
DOI: 10.1016/j.carbpol.2020.117572

Abstract

Hyaluronic acid (HA)-coated liposomes were designed for the targeted delivery of 17-hydroxy-jolkinolide B (HA-Lip-HJB). HA-Lip-HJB had a particle size of 130.8 ± 1.9 nm, zeta potential of -52.36 ± 1.91 mV, and encapsulation efficiency of 89.2 ± 1.5 %. In vitro cell experiments indicated that modification of HA-Lip-HJB increased its cytotoxicity and cellular uptake via CD44 receptor-mediated endocytosis pathway. Of particular importance is that HA-Lip-HJB suppressed cell migration and invasion by inhibiting epithelial-mesenchymal transition (EMT) process. Moreover, the HA-Lip-HJB displayed notable growth inhibition on tumor spheroids. Furthermore, in vivo tissue distribution and anti-tumor experiments carried on BALB/C mice bearing 4T1 tumor indicated that HA-Lip-HJB had strong tumor targeting and tumor suppression abilities. The results also demonstrated that HA-Lip-HJB inhibited tumor cells migration and colonization on the lung. Therefore, HA-Lip-HJB is a promising formulation for metastatic breast cancer therapy.

Keywords: 17-Hydroxy-jolkinolide B; Hyaluronic acid; Liposomes; Targeting drug delivery.

MeSH terms

Animals
Antineoplastic Agents / pharmacology
Cell Line, Tumor
Cell Movement
Diterpenes / administration & dosage*
Endocytosis
Epithelial-Mesenchymal Transition
Female
Hyaluronic Acid / chemistry*
In Vitro Techniques
Liposomes / chemistry*
Lung / metabolism
Mammary Neoplasms, Animal / drug therapy*
Mice
Mice, Inbred BALB C
Microscopy, Confocal
Neoplasm Metastasis / drug therapy*
Neoplasm Transplantation
Particle Size
Solubility
Spheroids, Cellular
Water / chemistry

Substances

Antineoplastic Agents
Diterpenes
Liposomes
Water
17-hydroxyjolkinolide B
Hyaluronic Acid