1. Thermoacoustic Imaging-Guided Thermo-Chemotherapy for Hepatocellular Carcinoma Sensitized by a Microwave-Responsive Nitric Oxide Nanogenerator.
- Author
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Wen L, Liu H, Hu C, Wei Z, Meng Y, Lu C, Su Y, Lu L, Liang H, Xu Q, and Zhan M
- Subjects
- Humans, Nitric Oxide therapeutic use, Microwaves, Contrast Media therapeutic use, Hydrogen Peroxide, Cisplatin therapeutic use, Tumor Microenvironment, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Antineoplastic Agents therapeutic use
- Abstract
Imaging-guided percutaneous microwave thermotherapy has been regarded as an important alternative nonsurgical therapeutic strategy for hepatocellular carcinoma (HCC) that provides excellent local tumor control and favorable survival benefit. However, providing a high-resolution, real-time, and noninvasive imaging technique for intraoperative guidance and controlling postoperative residual tumor recurrence are urgent needs for the clinical setting. In this study, a cisplatin (CDDP)-loaded nanocapsule (NPs@CDDP) with microwave responsive property was prepared to simultaneously serve as a contrast agent of emerging thermoacoustic imaging and a sensitizing agent of microwave thermo-chemotherapy. Accompanying the enzymolysis in the tumor microenvironment, the NPs@CDDP responsively release l-arginine (l-Arg) and CDDP. l-Arg with excellent microwave-absorbing property allowed it to serve as a thermoacoustic imaging contrast agent for accurately delineating the tumor and remarkably increasing tumor temperature under ultralow power microwave irradiation. Apart from the chemotherapeutic effect, CDDP elevated the intracellular H
2 O2 level through cascade reactions and further accelerated the continuous transformation of l-Arg to nitric oxide (NO), which endowed the NPs@CDDP with NO-generation capability. Notably, the high concentration of intracellular NO was proved to aggravate lipid peroxidation and greatly improved the efficacy of microwave thermo-chemotherapy. Thereby, NPs@CDDP was expected to serve as a theranostic agent integrating the functions of tumor microenvironment-responsive drug delivery system, contrast agent of thermoacoustic imaging, thermal sensitizing agent, and NO nanogenerator, which was promising to provide a potential imaging-guided therapeutic strategy for HCC.- Published
- 2023
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