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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.

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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.
Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, 215002, China.
School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou, 213164, China.
Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, 430074, China.
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing, 100190, China.


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.


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

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