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Biocompatible melanin based theranostic agent for in vivo detection and ablation of orthotopic micro-hepatocellular carcinoma

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Abstract

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.

Graphical abstract: Biocompatible melanin based theranostic agent for in vivo detection and ablation of orthotopic micro-hepatocellular carcinoma

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Supplementary files

Article information


Submitted
19 May 2020
Accepted
16 Jun 2020
First published
25 Jun 2020

Biomater. Sci., 2020, Advance Article
Article type
Paper

Biocompatible melanin based theranostic agent for in vivo detection and ablation of orthotopic micro-hepatocellular carcinoma

K. Chen, Q. Li, X. Zhao, J. Zhang, H. Ma, X. Sun, Q. Yu, Y. Zhang, C. Fang and L. Nie, Biomater. Sci., 2020, Advance Article , DOI: 10.1039/D0BM00825G

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