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A novel nanomissile targeting two biomarkers and accurately bombing CTCs with doxorubicin

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Abstract

Rare circulating tumor cells (CTCs) cause >50% of primary colorectal cancer survivors to develop deadly metastasis at 3–5 years after surgery; the current chemotherapies can do nothing about these cells. Herein, we synthesized a novel doxorubicin (DOX)-entrapped mesoporous silica nanoparticle (MSN), covalently-conjugated with two aptamers, for simultaneously targeting EpCAM and CD44, the typical surface biomarkers of colorectal CTCs. The nanomissile can specifically capture the metastasis-prone CTCs spiked in healthy human blood in a competitive-binding manner. The binding not only accurately delivers DOX into the cancer cells via the biomarker-mediated endocytosis to inhibit CTC viability through the DOX-dependent mechanism, but also inhibits the adhesion of cancer cells to the endothelium and the consequent transmembrane migration through the DOX-independent mechanism. The molecular entity of the conjugate and its pharmaceutical DOX encapsulation-releasing capacity are well-demonstrated via various physiochemical characterizations including gel electrophoresis, which proves the >8-hour biostability of the nanomissile in blood, long enough for it to chase CTCs in mice and synergistically inhibit the CTC-induced lung metastasis more potently than its single aptamer-conjugated counterparts and DOX itself. The present strategy may pave a new avenue for safe and effective cancer metastasis chemoprevention.

Graphical abstract: A novel nanomissile targeting two biomarkers and accurately bombing CTCs with doxorubicin

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Publication details

The article was received on 12 Jan 2017, accepted on 24 Mar 2017 and first published on 30 Mar 2017


Article type: Paper
DOI: 10.1039/C7NR00273D
Citation: Nanoscale, 2017, Advance Article
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    A novel nanomissile targeting two biomarkers and accurately bombing CTCs with doxorubicin

    Y. Gao, X. Xie, F. Li, Y. Lu, T. Li, S. Lian, Y. Zhang, H. Zhang, H. Mei and L. Jia, Nanoscale, 2017, Advance Article , DOI: 10.1039/C7NR00273D

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