TY - JOUR
T1 - Liposome-encapsulated anthraquinone improves efficacy and safety in triple negative breast cancer
AU - George, Thomashire A.
AU - Chen, Max M.
AU - Czosseck, Andreas
AU - Chen, Hsiang Pei
AU - Huang, Hsu Shan
AU - Lundy, David J.
N1 - Funding Information:
The authors are grateful for funding from Taiwan Ministry of Science and Technology ( MOST 108-2320-B-038-067 ) and Taipei Medical University ( TMU 107-AE1-B27 ). Work by T.A. George was partially supported by the Schlumberger Foundation Faculty for the Future program. Animal studies were supported by TMU Laboratory Animal Center. Cryo-EM was provided by Academia Sinica Cryo-EM Facility (Grant No. AS-CFII-108-110 ) and Taiwan Protein Project (Grant No. AS-KPQ-109-TPP2 and/or AS-KPQ-105-TPP ). We are also grateful to Dr. Alexander Wu for his critical advice and Dr. Jun-Jen Liu for providing equipment and guidance in liposome formation.
Publisher Copyright:
© 2021 The Authors
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
KW - Anthraquinone
KW - Breast cancer
KW - Liposome
KW - Polyethylene glycol
UR - http://www.scopus.com/inward/record.url?scp=85121965775&partnerID=8YFLogxK
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U2 - 10.1016/j.jconrel.2021.12.001
DO - 10.1016/j.jconrel.2021.12.001
M3 - Article
AN - SCOPUS:85121965775
SN - 0168-3659
VL - 342
SP - 31
EP - 43
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -
