A nanomedicine based combination therapy based on QLPVM peptide functionalized liposomal tamoxifen and doxorubicin against Luminal A breast cancer

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• 作者：Xiaoyou Wang ; MS^a ; Xianhui Chen ; MS^a ; Xiucong Yang ; MS^a ; Wei Gao ; PhD^a ; Bing He ; PhD^a ; Wenbing Dai ; PhD^a ; Hua Zhang ; PhD^a ; Xueqing Wang ; PhD^a ; Jiancheng Wang ; PhD^a ; Xuan Zhang ; PhD^a ; Zhifei Dai ; PhD^a ; ^c ; Qiang Zhang ; PhD^a ; ^b ; ^{zqdodo@bjmu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Nanomedicine based combinational therapy ; Penta-peptide QLPVM ; Luminal A breast cancer ; Tamoxifen ; Doxorubicin
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：12
• 期：2
• 页码：387-397
• 全文大小：2119 K

文摘

Though combination chemotherapy or antitumor nanomedicine is extensively investigated, their combining remains in infancy. Additionally, enhanced delivery of estrogen or its analogs to tumor with highly-expressed estrogen-receptor (ER) is seldom considered, despite its necessity for ER-positive breast cancer treatment. Here, nanomedicine based combination therapy using QLPVM conjugated liposomal tamoxifen (TAM) and doxorubicin (DOX) was designed and testified, where the penta-peptide was derived from Ku70 Bax-binding domain. Quantitative, semi-quantitative and qualitative approaches demonstrated the enhanced endocytosis and cytotoxicity of QLPVM conjugated sterically stabilized liposomes (QLPVM-SSLs) in vitro and in vivo. Mechanism studies of QLPVM excluded the possible electrostatic, hydrophobic or receptor–ligand interactions. However, as a weak cell-penetrating peptide, QLPVM significantly induced drug release from QLPVM-SSLs during their interaction with cells, which was favorable for drug internalization. These findings suggested that the nanomedicine based combination therapy using QLPVM-SSL-TAM and QLPVM-SSL-DOX might provide a rational strategy for Luminal A breast cancer.

From the Clinical Editor

Breast cancer remains a leading cause of mortality in women worldwide. Although combined therapy using hormonal antagonist and chemotherapy is the norm nowadays, the use of these agents together in a single delivery system has not been tested. Here, the authors investigated this approach using QLPVM conjugated liposomes in in-vitro and in-vivo models. The positive findings may provide a novel direction for breast cancer treatment in the near future.