Nanoliposome targeting in breast cancer is influenced by the tumor microenvironment

被引：26

作者：

Dumont, Nancy ^{[1
]}

Merrigan, Samantha ^{[1
]}

Turpin, Jason ^{[2
]}

Lavoie, Cynthia ^{[2
]}

Papavasiliou, Vasilios ^{[2
]}

Geretti, Elena ^{[1
]}

Espelin, Christopher W. ^{[1
]}

Luus, Lia ^{[1
]}

Kamoun, Walid S. ^{[1
]}

Ghasemi, Omid ^{[1
]}

Sahagian, G. Gary ^{[3
]}

Muller, William J. ^{[2
]}

Hendriks, Bart S. ^{[1
]}

Wickham, Thomas J. ^{[1
]}

Drummond, Daryl C. ^{[1
]}

机构：

[1] Merrimack Pharmaceut Inc, Cambridge, MA 02139 USA

[2] McGill Univ, Goodman Canc Ctr, Montreal, PQ, Canada

[3] Tufts Univ, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA

来源：

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE | 2019年 / 17卷

关键词：

Targeted nanoliposome delivery; Metastasis; Lymphatic flow; PEGYLATED-LIPOSOMAL DOXORUBICIN; RANDOMIZED PHASE-III; SPLICE VARIANT; EFFICACY; PLUS; HER2; COMBINATION; PACLITAXEL; SURVIVAL; TRIAL;

D O I：

10.1016/j.nano.2018.12.010

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

MM-302 is an anti-HER2 antibody-targeted pegylated liposomal doxorubicin designed to deliver doxorubicin specifically to HER2-expressing solid tumors. The delivery and activity of MM-302 were evaluated in orthotopic, transgenic, and intravenous breast cancer models expressing varying levels of HER2 that metastasize to some of the most common sites of dissemination for breast cancer, namely, lung. liver, and brain. Metastatic burden was quantified by gross evaluation, immunohistochemistry (IHC), and bioluminescent imaging. Liposome delivery was quantified by IHC and ex vivo fluorescent imaging. Unlike its non-targeted counterpart, pegylated liposomal doxorubicin (PLD), MM-302 showed activity at controlling both primary and metastatic tumor burden in all models tested. The effect of HER2-targeting was greatest in the lung where lymphatic vessel density and MM-302 delivery were highest. Our data indicate that the therapeutic advantage of actively targeting a nanoliposome with an antibody is influenced by both target expression and the tumor microenvironment. (C) 2019 Elsevier Inc. All rights reserved.

引用

页码：71 / 81

页数：11

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