Indocyanine Green-Loaded Nanobubbles Targeting Carbonic Anhydrase IX for Multimodal Imaging of Renal Cell Carcinoma

作者全名："Zhong, Chengjie; Chen, Jiajiu; Ling, Yi; Liu, Deng; Xu, Jing; Wang, Luofu; Ge, Chengguo; Jiang, Qing"

作者地址："[Zhong, Chengjie] Chongqing Med Univ, Clin Med Coll 2, Chongqing 400016, Peoples R China; [Chen, Jiajiu; Xu, Jing; Wang, Luofu] Army Med Univ, Daping Hosp, Dept Urol, Chongqing 400038, Peoples R China; [Ling, Yi; Liu, Deng] Army Med Univ, Southwest Hosp, Dept Ultrasound, Chongqing 400042, Peoples R China; [Ge, Chengguo; Jiang, Qing] Chongqing Med Univ, Affiliated Hosp 2, Dept Urol, Chongqing 400010, Peoples R China"

通信作者："Ge, CG; Jiang, Q (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Urol, Chongqing 400010, Peoples R China."

来源：INTERNATIONAL JOURNAL OF NANOMEDICINE

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000995430900001

JCR分区：Q1

影响因子：6.6

年份：2023

卷号：18

期号：　

开始页：2757

结束页：2776

文献类型：Article

关键词：contrast-enhanced ultrasound imaging; photoacoustic imaging; renal cell carcinoma; carbonic anhydrase IX; targeted nanobubble; fluorescence imaging

摘要："Background and Purpose: The early diagnosis and differential diagnosis of renal cell carcinoma (RCC) has always been a clinical difficulty and a research focus. Carbonic anhydrase IX (CA IX) is highly expressed on the cell membrane of RCC but is not expressed in normal renal tissues. In this study, nanobubbles (NBs) targeting CA IX with ultrasound and photoacoustic multimodal imaging capabilities were prepared to explore a new method for the diagnosis and differential diagnosis of RCC.Methods: Indocyanine green (ICG)-loaded lipid NBs (ICG-NBs) were prepared by using the filming rehydration method, and antiCA IX polypeptides (ACPs) were attached to their surfaces to prepare CA IX-targeted NBs (ACP/ICG-NBs). The particle size, zeta potential and ICG encapsulation efficiency of these nanobubbles were measured, and their specific targeting and binding abilities to RCC cells were determined. The in vitro and in vivo ultrasound, photoacoustic and fluorescence imaging characteristics of these nanobubbles were also assessed.Results: The particle size of the ACP/ICG-NBs was 475.9 nm in diameter, and their zeta potential was -2.65 mV. Laser confocal microscopy and flow cytometry both confirmed that ACP/ICG-NBs had specific binding activity and ideal affinity to CA IX-positive RCC cells (786-O) but not to CA IX-negative RCC cells (ACHN). The intensities of the in vitro ultrasound, photoacoustic and fluorescence imaging were positively correlated with the concentrations of ACP/ICG-NBs. In in vivo ultrasound and photoacoustic imaging experiments, ACP/ICG-NBs exhibited specific enhanced ultrasound and photoacoustic imaging effects in 786-O xenograft tumors. Conclusion: The ICG- and ACP-loaded targeted nanobubbles that we prepared had the capability of ultrasound, photoacoustic and fluorescence multimodal imaging and could specifically enhance the ultrasound and photoacoustic imaging of RCC xenograft tumors. This outcome has potential clinical application value for the diagnosis of RCC at the early stage and the differential diagnosis of benign and malignant kidney tumors."

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