Liposome-encapsulated anthraquinone improves efficacy and safety in triple negative breast cancer

Thomashire A George; Max M Chen; Andreas Czosseck; Hsiang-Pei Chen; Hsu-Shan Huang; David J Lundy

doi:10.1016/j.jconrel.2021.12.001

Liposome-encapsulated anthraquinone improves efficacy and safety in triple negative breast cancer

J Control Release. 2022 Feb:342:31-43. doi: 10.1016/j.jconrel.2021.12.001. Epub 2021 Dec 8.

Authors

Thomashire A George¹, Max M Chen², Andreas Czosseck², Hsiang-Pei Chen³, Hsu-Shan Huang⁴, David J Lundy⁵

Affiliations

¹ International PhD Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan.
² Graduate Institute of Biomedical Materials & Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, 11031, Taiwan.
³ School of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan.
⁴ Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan.
⁵ International PhD Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan; Graduate Institute of Biomedical Materials & Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, 11031, Taiwan. Electronic address: dlundy@tmu.edu.tw.

PMID: 34896187
DOI: 10.1016/j.jconrel.2021.12.001

Abstract

Breast cancer is the most common cancer among women and a leading cause of death worldwide. Triple negative breast cancer (TNBC) is a highly aggressive subtype which is the most challenging to treat. Due to heterogeneity and a lack of specific molecular targets, small molecule-based chemotherapy is the preferred course of treatment. However, these drugs have high toxicity due to off-target effects on healthy tissues, and tumors may develop resistance. Here, we present a polyethylene glycol-modified nanoscale liposomal formulation (LipoRV) of a new anthraquinone derivative which has potent effects on multiple TNBC cell lines. LipoRV readily inhibited the cell cycle, induced cell apoptosis, and reduced long-term proliferative potential of TNBC cells. In a xenograft animal model, LipoRV successfully cleared tumors and demonstrated a good safety profile, without detrimental effects on biochemical markers. Finally, RNA sequencing of LipoRV-treated TNBC cells was carried out, indicating that LipoRV may have immunomodulatory properties. These findings demonstrate that a liposomal anthraquinone-based molecule has excellent promise for TNBC therapy in the future.

Keywords: Anthraquinone; Breast cancer; Liposome; Polyethylene glycol.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anthraquinones / pharmacology
Anthraquinones / therapeutic use
Apoptosis
Cell Line, Tumor
Cell Proliferation
Female
Humans
Liposomes / therapeutic use
Triple Negative Breast Neoplasms* / metabolism
Xenograft Model Antitumor Assays

Substances

Anthraquinones
Liposomes