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Vol. 16 (2024)

Injectable Nanorobot-Hydrogel Superstructure for Hemostasis and Anticancer Therapy of Spinal Metastasis

https://doi.org/10.1007/s40820-024-01469-3
Qing Chen
Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China
Miao Yan
Department of Chemistry, Fudan University, Shanghai 200438, People’s Republic of China
Annan Hu
Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China
Bing Liang
Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China
Hongwei Lu
Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China
Lei Zhou
Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China
Yiqun Ma
Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China
Chao Jia
Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China
Dihan Su
Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China
Biao Kong
Department of Chemistry, Fudan University, Shanghai 200438, People’s Republic of China
Wei Hong
Department of Geriatrics and Gerontology, Huadong Hospital, Fudan University, Shanghai 200438, People’s Republic of China
Libo Jiang
Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China
Jian Dong
Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China

Corresponding Author: Jian Dong

dong.jian@zs-hospital.sh.cn

Nano-Micro Letters, Vol. 16 (2024), Article Number: 259

Abstract

Surgery remains the standard treatment for spinal metastasis. However, uncontrolled intraoperative bleeding poses a significant challenge for adequate surgical resection and compromises surgical outcomes. In this study, we develop a thrombin (Thr)-loaded nanorobot-hydrogel hybrid superstructure by incorporating nanorobots into regenerated silk fibroin nanofibril hydrogels. This superstructure with superior thixotropic properties is injected percutaneously and dispersed into the spinal metastasis of hepatocellular carcinoma (HCC) with easy bleeding characteristics, before spinal surgery in a mouse model. Under near-infrared irradiation, the self-motile nanorobots penetrate into the deep spinal tumor, releasing Thr in a controlled manner. Thr-induced thrombosis effectively blocks the tumor vasculature and reduces bleeding, inhibiting tumor growth and postoperative recurrence with Au nanorod-mediated photothermal therapy. Our minimally invasive treatment platform provides a novel preoperative therapeutic strategy for HCC spinal metastasis effectively controlling intraoperative bleeding and tumor growth, with potentially reduced surgical complications and enhanced operative outcomes.


Highlights:
1 Site-selective superassembly was used to synthesize a nanorobot with bionic rod-shaped head/hollow tail structure, exhibiting strong photothermal effect, high drug loading capacity, precise and controlled drug release, and excellent motility.
2 Injectable regenerated silk fibroin (RSF) nanofibril hydrogels were developed via simple sonication, offering significant production, structural, and performance advantages.
3 Nanorobot/thrombin (Thr)/RSF nanofibril hydrogels reduced intraoperative bleeding of hepatocellular carcinoma (HCC) spinal metastasis, provided starvation embolization, and prevented post-surgery recurrence.
4 Nanorobot/Thr/RSF nanofibril hydrogels inhibited blood supply to residual tumors and reduced neovascularization, inhibiting post-surgery HCC spinal metastasis recurrence.

Keywords

Silk fibroin Nanofibril hydrogels Nanorobots Thrombin Spinal metastasis
Chen, Qing, Miao Yan, Annan Hu, Bing Liang, Hongwei Lu, Lei Zhou, Yiqun Ma, Chao Jia, Dihan Su, Biao Kong, Wei Hong, Libo Jiang, and Jian Dong. 2024. “Injectable Nanorobot-Hydrogel Superstructure for Hemostasis and Anticancer Therapy of Spinal Metastasis”. Nano-Micro Letters 16 (August):259. https://doi.org/10.1007/s40820-024-01469-3.
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