Journal
BIOMATERIALS
Volume 139, Issue -, Pages 1-11Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2017.05.037
Keywords
Near-infrared laser; Nanobomb; Tumor neovasculature; Photoacoustic imaging; Antiangiogenesis therapy
Funding
- 973 Program [2013CB 933800]
- National Natural Science Foundation of China [21390411, 21535004, 21227005, 21305081, 21575082, 21605097]
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Attacking the supportive vasculature network of a tumor offers an important new avenue for cancer therapy. Herein, a near-infrared (NIR) laser-activated nanobomb was developed as a noninvasive and targeted physical therapeutic strategy to effectively disrupt tumor neovasculature in an accurate and expeditious manner. This nanobomb was rationally fabricated via the encapsulation of vinyl azide (VA) into c(RGDfE) peptide-functionalized, hollow copper sulfide (HCuS) nanoparticles. The resulting RGD@HCuS(VA) was selectively internalized into integrin alpha(v)beta(3)-expressing tumor vasculature endothelial cells and dramatically increased the photoacoustic signals from the tumor neovasculature, achieving a maximum signal-to-noise ratio at 4 h post-injection. Upon NIR irradiation, the local temperature increase triggered VA to release N-2 bubbles rapidly. Subsequently, these N-2 bubbles could instantly explode to destroy the neovasculature and further induce necrosis of the surrounding tumor cells. A single-dose injection of RGD@HCuS(VA) led to complete tumor regression after laser irradiation, with no tumor regrowth for 30 days. More importantly, high-resolution photoacoustic angiography, combined with excellent biodegradability, facilitated the precise destruction of tumor neovasculature by RGD@HCuS(VA) without damaging normal tissues. These results demonstrate the great potential of this nanobomb for clinical translation to treat cancer patients with NIR laser-accessible orthotopic tumors. (C) 2017 Elsevier Ltd. All rights reserved.
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