Early diagnosis and therapy of hepatocellular carcinoma (HCC) is critical to improve the five-year survival rates of patients. Theranostic agents synergized with photothermal ablation are expected to realize the early detection and treatment of orthotopic HCC. However, conventional metallic nanoagents are limited by their potential bio-toxicity to surrounding normal organs. Recently, endogenous biological melanin pigments have been utilized to develop nanoplatforms due to their excellent biocompatibility and degradability. Whereas, the insufficient capability of PEGylated melanin nanoparticles (PEG-MNPs) in photoacoustic (PA) imaging limits their further biomedical applications. Paradoxically, it is difficult to meet these two different requirements. Herein, a multifunctional nanoagent based on melanin (MNPs) conjugating the near-infrared (NIR) dye IR820 was successfully designed and fabricated. Encapsulation by polyethylene glycol (PEG) renders the solubility in water and allows the physical absorption of IR820 for enhanced photoacoustic (PA) performance and photothermal therapy. Besides, PEG coating on the surface of IR820-PEG-MNPs resulted in a reduction in swallowing in the reticuloendothelial system of the liver and spleen, prolonging the circulation time in the blood and increasing the accumulation in the tumor. The IR820-PEG-MNPs displayed satisfactory PA and T₁-weighted magnetic resonance imaging (MRI) signals in aqueous solution as well as strong photothermal efficiency. Compared with prior injection, PA/MR signals of the tumor region were enhanced by 4.13- and 1.60-fold, respectively, which could effectively detect lesions smaller than ∼1.8 mm. Furthermore, the high photothermal conversion efficiency (40.2%) endowed the IR820-PEG-MNPs with the capability of selectively ablating tumors in orthotopic HCC mouse models under the guidance of PA/MR imaging. This work broadens the biomedical applications of melanin-based agent, which are promising for the precise diagnosis of orthotopic micro HCC and imaging guided photothermal ablation.

中文翻译：

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用于体内检测和消融原位微肝细胞癌的基于生物相容性黑色素的治疗剂。

肝细胞癌（HCC）的早期诊断和治疗对于提高患者的五年生存率至关重要。与光热消融协同的治疗药物有望实现原位肝癌的早期发现和治疗。然而，常规的金属纳米剂由于其对周围正常器官的潜在生物毒性而受到限制。最近，由于其优异的生物相容性和可降解性，内源性生物黑色素颜料已被用于开发纳米​​平台。然而，聚乙二醇化黑色素纳米颗粒（PEG-MNPs）在光声（PA）成像中的能力不足限制了其进一步的生物医学应用。矛盾的是，很难满足这两个不同的要求。在这里 一种基于黑色素（MNPs）结合近红外（IR）染料IR820的多功能纳米剂已被成功设计和制造。聚乙二醇（PEG）的封装可提高其在水中的溶解度，并允许IR820的物理吸收，从而增强光声（PA）性能和光热疗法。此外，IR820-PEG-MNPs表面的PEG涂层可减少吞咽肝和脾的网状内皮系统，延长血液的循环时间并增加肿瘤的蓄积。IR820-PEG-MNPs显示出令人满意的PA和 此外，IR820-PEG-MNPs表面的PEG涂层导致减少了肝脏和脾的网状内皮系统的吞咽，延长了血液的循环时间并增加了肿瘤的积累。IR820-PEG-MNPs显示出令人满意的PA和 此外，IR820-PEG-MNPs表面的PEG涂层导致减少了肝脏和脾的网状内皮系统的吞咽，延长了血液的循环时间并增加了肿瘤的积累。IR820-PEG-MNPs显示出令人满意的PA和水溶液中的T ₁加权磁共振成像（MRI）信号以及强大的光热效率。与之前的注射相比，肿瘤区域的PA / MR信号分别提高了4.13倍和1.60倍，可以有效地检测小于1.8 mm的病变。此外，高的光热转化效率（40.2％）使IR820-PEG-MNP具有在PA / MR成像指导下选择性切除原位HCC小鼠模型中肿瘤的能力。这项工作拓宽了基于黑色素的药物的生物医学应用，这对于精确诊断原位微HCC和成像引导的光热消融是有希望的。