ZFIN ID: ZDB-PUB-190808-15
Development of a Liposomal Formulation of Acetyltanshinone IIA for Breast Cancer Therapy
Wang, Q., Luo, M., Wei, N., Chang, A., Luo, K.Q.
Date: 2019
Source: Molecular pharmaceutics   16(9): 3873-3886 (Journal)
Registered Authors: Chang, Alex (Kuok Weai), Luo, Kathy Qian
Keywords: acetyltanshinone IIA (ATA), anti-breast cancer drugs, bioavailability, mPEG-liposomes, pharmacokinetics, toxicity study
MeSH Terms:
  • Animals
  • Antineoplastic Agents/chemistry*
  • Antineoplastic Agents/pharmacokinetics
  • Antineoplastic Agents/therapeutic use*
  • Biological Availability
  • Breast Neoplasms/drug therapy*
  • Cell Survival/drug effects
  • Drug Compounding/methods*
  • Female
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Larva/drug effects
  • Liposomes/chemistry*
  • MCF-7 Cells
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Phenanthrenes/chemistry*
  • Phenanthrenes/pharmacokinetics
  • Phenanthrenes/therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Burden/drug effects
  • Xenograft Model Antitumor Assays
  • Zebrafish/embryology
PubMed: 31389706 Full text @ Mol. Pharm.
Acetyltanshinone IIA (ATA), synthesized in our group exhibiting good anti-breast cancer effects, is expected to replace the commonly used anti-ER+ breast cancer (breast cancer cells overexpressing the estrogen receptor) drug tamoxifen. To promote the clinical progress of ATA, polyethylene glycol (PEG)-modified liposomes were used to encapsulate ATA along with improving its bioavailability and in vivo anticancer efficiency. The resulting liposomal ATA exhibited a spherical shape with an average size of 188.5 nm. In vitro evaluations showed that liposomal ATA retained the anti-breast cancer efficacy of ATA while exerting much less cytotoxicity toward noncancerous cells. Significantly, pharmacokinetics analysis showed that the AUC0-24h of liposomal ATA was 59 times higher than that of free ATA, demonstrating increased bioavailability of ATA. Preclinical experiments demonstrated that liposomal ATA reduced the growth of ER-positive human breast tumor xenografts by 73% in nude mice, and the liposomal ATA exhibited a much lower level of toxicity than that of free ATA with respect to zebrafish larval mortality, body formation, and heart function during development. Moreover, 7-day and 21-day tissue toxicity levels were determined in mice by intravenous administration of a maximum dosage of liposomal ATA (120 mg/kg). The results showed no obvious tissue damage in major organs, including the heart, liver, spleen, kidney, and brain. In summary, we have developed a clinical formulation of liposomal ATA with the high bioavailability and potent efficacy for the treatment of ER-positive breast cancer.