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Research Article

Ultrasound-visualized nanocarriers with siRNA for targeted inhibition of M2-like TAM polarization to enhance photothermal therapy in NSCLC

Wenhao Lv1,2,§, Chen Xu2,§, Hao Wu1, Yangyang Zhu1, Ozioma Udochukwu Akakuru2, Hui Du2, Fang Nie1( ), Aiguo Wu2( ), Juan Li2( )
Ultrasound Medical Center, Lanzhou University Second Hospital, Gansu Province Clinical Research Center for Ultrasonography, Gansu Province Medical Engineering Research Center for Intelligence Ultrasound, Lanzhou 730000, China
Cixi Institute of Biomedical Engineering, International Cooperation Base of Biomedical Materials Technology and Application, Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Materials and Devices, Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, CAS, Ningbo 315201, China

§ Wenhao Lv and Chen Xu contributed equally to this work.

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Graphical Abstract

An ultrasound-visualized nanocarrier is developed to deliver siRNA that inhibits M2 macrophage polarization and enhances the therapeutic effectiveness of photothermal therapy for non-small cell lung cancer.

Abstract

Photothermal therapy (PTT) has received a lot of attention as a promising strategy for eliminating tumors quickly. However, the unavoidable inflammatory response during the treatment might result in a high concentration of M2-like tumor-associated macrophages (TAMs), increasing the risk of tumor recurrence and metastasis. To address this problem, gold-based nanocarriers (PGMP-small interfering RNA (siRNA) nanoparticles (NPs)) containing STAT6siRNA, that inhibited M2-like TAM polarization, were designed and investigated for PTT and gene therapy of non-small cell lung cancer (NSCLC). In an NSCLC model, the nanocarriers demonstrated excellent siRNA delivery ability and a high gene transfection rate of up to 90% in macrophages, thus inhibiting the polarization of about 87% of M2-like TAMs and effectively suppressing the invasion and metastasis of NSCLC. Meanwhile, the unique gold nanosphere structure offered improved PTT and contrast-enhanced ultrasound imaging, thus contributing to the efficient elimination and real-time monitoring of the tumor tissues. These nanocarriers with combined gene and photothermal therapeutic capabilities improved the efficacy of single-modality treatment, and showed the potential to inhibit cancer cell recurrence and metastasis to ultimately cure NSCLC.

Keywords

gold-based nanocarriersmall interfering RNA (siRNA) deliveryphotothermal therapyM2-like tumor-associated macrophages (TAMs)contrast-enhanced ultrasound imagingnon-small cell lung cancer (NSCLC)

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Nano Research
Volume 16 Issue 1,
January 2023
Pages 882-893
DOI: 10.1007/s12274-022-4767-7
Cite this article:
Lv W, Xu C, Wu H, et al. Ultrasound-visualized nanocarriers with siRNA for targeted inhibition of M2-like TAM polarization to enhance photothermal therapy in NSCLC. Nano Research, 2023, 16(1): 882-893. https://doi.org/10.1007/s12274-022-4767-7
Topics:
NanobiotechnologyNanoprobesTheranostics

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Received: 06 May 2022
Revised: 12 July 2022
Accepted: 12 July 2022
Published: 30 August 2022
© Tsinghua University Press 2022
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