Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai, Guangdong 519000, P.R. China.
Department of General Surgery, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai 519000, China.
ACS Appl Mater Interfaces. 2023 Mar 1;15(8):10477-10491. doi: 10.1021/acsami.2c22523. Epub 2023 Feb 15.
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 HO 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.
影像引导经皮微波热疗已被视为治疗肝细胞癌（HCC）的一种重要非手术治疗策略，可提供出色的局部肿瘤控制和良好的生存获益。然而，为临床提供一种高分辨率、实时、非侵入性的影像技术，用于术中引导和控制术后残留肿瘤复发，是临床迫切需要解决的问题。在本研究中，制备了一种具有微波响应特性的顺铂（CDDP）负载纳米胶囊（NPs@CDDP），同时作为新兴的热声成像造影剂和微波热化疗增敏剂。伴随着肿瘤微环境中的酶解，NPs@CDDP 响应性地释放 l-精氨酸（l-Arg）和 CDDP。l-Arg 具有出色的微波吸收特性，可作为热声成像造影剂，准确描绘肿瘤，并在超低功率微波辐射下显著提高肿瘤温度。除了化疗效果外，CDDP 通过级联反应提高了细胞内 HO 水平，进一步加速了 l-Arg 向一氧化氮（NO）的连续转化，使 NPs@CDDP 具有 NO 生成能力。值得注意的是，细胞内高浓度的 NO 被证明会加重脂质过氧化，并大大提高微波热化疗的疗效。因此，NPs@CDDP 有望作为一种集肿瘤微环境响应性药物传递系统、热声成像造影剂、热敏剂和 NO 纳米发生器功能于一体的治疗诊断试剂，为 HCC 提供一种潜在的影像引导治疗策略。
