Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
CAS Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China.
ACS Nano. 2020 Oct 27;14(10):12679-12696. doi: 10.1021/acsnano.0c01453. Epub 2020 Sep 17.
Hepatocellular carcinoma (HCC) is a common and highly malignant tumor that is prone to recurrence and metastasis and has no effective treatment. Unsurprisingly, its prognosis is quite poor; early detection methods and effective low-toxicity treatments are urgently needed. To achieve these goals, we designed a multifunctional, U.S. Food and Drug Administration-approved Prussian blue (PB) nanoparticle (NP) with a porous metal organic frame loaded with sorafenib (SF), conjugated with HCC-specific targeting peptide SP94 and the near-infrared dye cyanine (Cy)5.5. These NPs are amenable to multimodal imaging for dynamic monitoring of their biodistribution and tumor-targeting effects. The SP94-PB-SF-Cy5.5 NPs achieved targeted delivery and controlled SF release and exhibited good photothermal effects. In this strategy, photothermal therapy and SF treatment complement each other, reducing the side effects of SF and achieving a therapeutic effect without local tumor recurrence. In addition, the catalase-like ability of the NPs alleviates tumor hypoxia, and their photothermal effects induce immunogenic cell death, leading to the release of tumor-associated antigens. These effects combine to trigger an antitumor immune response; the NPs also displayed promising inhibitory effects on tumor metastasis and recurrence and produced an abscopal effect and long-term immunological memory when combined with antiprogrammed death-ligand 1 (PD-L1) immunotherapy. These safe, multifunctional NPs represent a valuable treatment option for HCC. In addition, this next-generation treatment model may provide some ideas for the management of HCC and other cancers.
肝细胞癌（HCC）是一种常见且高度恶性的肿瘤，易复发和转移，且目前尚无有效的治疗方法。因此，其预后较差也就不足为奇了；目前迫切需要开发早期检测方法和有效的低毒治疗方法。为了实现这些目标，我们设计了一种多功能的、经美国食品和药物管理局批准的普鲁士蓝（PB）纳米颗粒（NP），其具有负载索拉非尼（SF）的多孔金属有机框架，与 HCC 特异性靶向肽 SP94 和近红外染料 Cy5.5 相共轭。这些 NP 可进行多模态成像，以动态监测其生物分布和肿瘤靶向效果。SP94-PB-SF-Cy5.5 NP 实现了靶向递药和 SF 的控制释放，并表现出良好的光热效应。在该策略中，光热治疗和 SF 治疗相辅相成，降低了 SF 的副作用，实现了无局部肿瘤复发的治疗效果。此外，NP 的类过氧化物酶能力缓解了肿瘤缺氧，其光热效应诱导免疫原性细胞死亡，导致肿瘤相关抗原的释放。这些作用共同引发抗肿瘤免疫反应；NP 还对肿瘤转移和复发具有明显的抑制作用，并与抗程序性死亡配体 1（PD-L1）免疫疗法联合使用时产生了远隔效应和长期免疫记忆。这些安全、多功能的 NP 为 HCC 提供了一种有价值的治疗选择。此外，这种下一代治疗模式可能为 HCC 和其他癌症的治疗提供一些思路。
