Temperature sensitive nanogels for real-time imaging during transcatheter arterial embolization

ABSTRACT

Several vascular embolization materials are commonly used in clinical practice, however, having application defects of varying degrees, such as poor intraoperative imaging and easy recanalization of embolized blood vessels, they are challenging for application during Transcatheter arterial embolization (TAE). Thus, an intraoperative visible vascular embolization material with good embolization effect and biocompatibility can improve transcatheter arterial embolization clinical efficacy to some extent. Our study aimed to synthesize a novel vascular embolization material that can achieve complete embolization of arterial trunks and peripheral vessels, namely poly (N-isopropyl acrylamide)-co-acrylic acid nanogel (NIPAM-co-AA). Iohexol 200 mg/mL was co-assembled with 7 wt% NIPAM-co-AA nanogel to create an intelligent thermosensitive radiopaque nanogel (INCA), which achieves a good intraoperative imaging effect and is convenient for transcatheter arterial bolus injection due to its good fluidity and temperature-sensitive sol-gel phase transition. The normal rabbit kidney embolism model further confirmed that INCA could effectively use Digital subtraction angiography (DSA) to achieve intraoperative imaging, and real-time monitoring of the embolization process could avoid mis-embolization and leakage. Meanwhile, in a 42-day study, INCA demonstrated an excellent embolization effect on the right renal artery of New Zealand white rabbits, with no vascular recanalization and ischemic necrosis and calcification remaining. As a result, this radiopaque thermosensitive nanogel has the potential to be an intelligent thermosensitive medical vascular embolization material, providing dual benefits in TAE intraoperative imaging and long-term postoperative embolization while effectively addressing the shortcomings and challenges of commonly used clinical vascular embolization agents.

KEYWORDS:

• Embolization
• X-ray visible
• high-strength nanogels
• real-time imaging
• temperature-sensitive

Abbreviations

TAE: Transcatheter arterial embolization; TACE: Transcatheter arterial chemo-embolization; NIPAM-co-AA: poly (N-isopropyl acrylamide)-co-acrylic acid nanogel; INCA: Intelligent thermosensitive radiopaque nanogel; DSA: Digital subtraction angiography; NIPAM: N-isopropyl acrylamide; AA: Acrylic acid; AAPH: 2,2’-azobis(2-methylpropionamidine) dihydrochloride; STAC: Octadecyl trimethyl ammonium chloride; MBA: N, N’-methylene bisacrylamide; PVA: polyvinyl alcohol.

Acknowledgments

Thanks to the Scientific Research Platform of the Medical Research Institute of Hubei University of Science and Technology, the Life Science Research Center of Huazhong University of Science and Technology, the Analysis and Testing Center of Huazhong University of Science and Technology, and the Radiology Department of Xianning Central Hospital of Hubei Province for providing the corresponding equipment and analysis.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author Contributions

Ling Li designed and conceived the experiment of the whole project. Wenjing Xie, Hongfu Zhou and Anran Guo conducted the synthesis, preparation, characterization and animal experiments of the materials, analyzed the experimental data. Hongan Tian, Bin Chen, Sanming Hu and Ling Li performed surgical operations on the experimental rabbits and provided technical support for CT imaging and DSA. Houqiang Yu and Min Zheng assisted in completing the animal experiments. All authors read and approve this submitted manuscript. Ling Li and Hongan Tian are the corresponding authors.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (82003308), PhD Start-up Fund of Hubei University of Science and Technology (BK202118, BK202119).