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Research Article

The immune-chemo-embolization effect of temperature sensitive gold nanomedicines against liver cancer

Yiming Liu1,6,§, Dingwen Shi2,§, Yanqiao Ren1,6,§, Ling Li3, Yanbing Zhao2,4( ), Chuansheng Zheng1,6( ), Xiangliang Yang2,4,5
Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
School of Biomedical Engineering, Hubei University of Science and Technology, Xianning 437100, China
Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, Huazhong University of Science and Technology, Wuhan 430074, China
GBA Research Innovation Institute for Nanotechnology, Guangzhou 510530, China
Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China

§ Yiming Liu, Dingwen Shi, and Yanqiao Ren contributed equally to this work.

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Graphical Abstract

Gold nanoparticles and doxorubicin (DOX) were both modified into the temperature sensitive polymers. Besides the computed tomography (CT) imaging caused by gold nanoparticles, the slowly release of DOX could enhance the tumor apoptosis, which increased the infiltration of CD3+ and CD8+ cells, and improve the tumor immune microenvironment, thereby inhibiting the tumor growth and metastasis.

Abstract

Although transcatheter arterial chemo-embolization (TACE) plays a key role on clinical treatment of hepatocellular carcinoma (HCC), it was greatly limited by the poor synergistic effect between chemotherapeutics and physical embolization to tumor-feeding arteries. In the present work, a temperature sensitive polymer poly(N-isopropylacrylamide-b-methacrylic acid) (PNA), which was modified with gold nanoparticles (AuNP@PNA), was successfully used to encapsulate doxorubicin (DOX) by electrostatic binding with their carboxyl groups. The resultant gold nanomedicines (AuNP@PNA/DOX) exhibited temperature responsive sol-gel phase transition, favorable shear thinning effect and X-ray angiography. By in vivo evaluation of vascular embolization on VX2-tumor-bearing rabbits, AuNP@PNA/DOX exhibited far better antitumor efficacy than Lipiodol/DOX, on either tumor growth inhibition, proliferation, apoptosis, necrosis or anti-metastasis. Owing to sufficient embolization to tumor vascular networks, AuNP@PNA/DOX down-regulated the expression levels of HIF-1α, VEGF and MMP-9, and prompted more efficient activation on CD3+/CD8+ T cells and the related cytokines, suggesting the synergistic effect between AuNP@PNA and DOX on the improvement of post-operative tumor immunosuppressive microenvironment. With their favorable pharmcokinetics and biocompatibility, AuNP@PNA/DOX is promising to be developed as a multi-functional artery-imaging/embolic agent with immune-chemo-embolization for enhancing TACE efficacy on HCC.

Keywords

temperature sensitive nanogelsgold nanoparticlestranscatheter arterial chemo-embolization (TACE)antitumor immune response

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Nano Research
Volume 16 Issue 2,
February 2023
Pages 2749-2761
DOI: 10.1007/s12274-022-4921-2
Cite this article:
Liu Y, Shi D, Ren Y, et al. The immune-chemo-embolization effect of temperature sensitive gold nanomedicines against liver cancer. Nano Research, 2023, 16(2): 2749-2761. https://doi.org/10.1007/s12274-022-4921-2
Topics:
Drug deliveryGelsGold nanoparticlesTemperature

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Received: 30 June 2022
Revised: 13 August 2022
Accepted: 16 August 2022
Published: 20 October 2022
© Tsinghua University Press 2022
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