4.7 Article

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

Journal

CARBOHYDRATE POLYMERS
Volume 257, Issue -, Pages -

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2020.117572

Keywords

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

Funding

  1. National Natural Science Foundation of China [81873172]
  2. Heilongjiang Provincial Natural Science Foundation of China [LC2018016]
  3. China Postdoctoral Science Foundation [2019M661321]
  4. Scientific Research Fund of Qiqihar Academy of Medical Sciences, China [QMSI2017LX-01, QMSI2017LX-02, QMSI2019M-03]
  5. Scientific Research Fund of Heilongjiang Provincial Education Department, China [2019-KYYWF-1275, 2018-KYYWF-0081, 2017-KYYWF-0694]
  6. Basic Research Foundation of Qiqihar Medical University [QY2017Q-03]

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Hyaluronic acid-coated liposomes targeted the delivery of 17-hydroxy-jolkinolide B with increased cytotoxicity and cellular uptake via CD44 receptor-mediated endocytosis. These liposomes suppressed cell migration and invasion, inhibited epithelial-mesenchymal transition, and demonstrated notable growth inhibition on tumor spheroids. In vivo experiments on mice showed strong tumor targeting and suppression abilities, making them a promising therapy for metastatic breast cancer.
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.

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