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Small. 2018 Dec;14(50):e1802745. doi: 10.1002/smll.201802745. Epub 2018 Oct 7.

A NanoFlare-Based Strategy for In Situ Tumor Margin Demarcation and Neoadjuvant Gene/Photothermal Therapy.

Author information

1
State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China.
2
Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, 215002, China.
3
School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou, 213164, China.
4
Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, 430074, China.
5
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing, 100190, China.

Abstract

Accurate tumor margin demarcation in situ remains a paramount challenge. Herein, a NanoFlare (also known as spherical-nucleic-acid technology) based strategy is reported for in situ tumor margin delineation by transforming and amplifying the pathophysiological redox signals of tumor microenvironment. The NanoFlare designed (named AuNS-ASON) is based on gold nanostar (AuNS) coated with a dense shell of disulfide bridge-inserted and cyanine dyes-labeled antisense oligonucleotides (ASON) targeting survivin mRNA. The unique anisotropic ASON-spike nanostructure endows the AuNS-ASON with universal cellular internalization of tumor cells, while the disulfide bridge inserted confers response specificity toward redox activation. In vitro experiments demonstrate that the AuNS-ASON can discriminate tumor cells rapidly with activated fluorescence signals (>100-fold) in 2 h, and further achieve synergistic gene/photothermal tumor cells ablation upon near-infrared laser irradiation. Remarkably, in situ tumor margin delineation with high accuracy and outstanding spatial resolution (<100 µm) in mice bearing different tumors is obtained based on the AuNS-ASON, providing intraoperative guidance for tumor resection. Moreover, the AuNS-ASON can enable efficient neoadjuvant gene/photothermal therapy before surgery to reduce tumor extent and increase resectability. The concept of NanoFlare-based microenvironment signal transformation and amplification could be used as a general strategy to guide the design of activatable nanoprobes for cancer theranostics.

KEYWORDS:

NanoFlare; fluorescence turn-on; redox signals; tumor margin demarcation; tumor microenvironment

PMID:
30294858
DOI:
10.1002/smll.201802745
[Indexed for MEDLINE]

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