Vitamin A-modified melanin nanoparticles for photoacoustic imaging-guided photothermal therapy of hepatic fibrosis.

Hepatic fibrosis, a prevalent pathological process in chronic liver diseases, represents a significant global public health challenge due to its progression toward severe conditions such as cirrhosis and hepatocellular carcinoma. Despite extensive research efforts, no specific anti-fibrotic agents have been approved for clinical use, underscoring the urgent need for innovative therapeutic strategies. Activated hepatic stellate cells (HSCs) excessively produce extracellular matrix (ECM) components like collagen, deteriorating fibrosis progression. HSCs, storing lipid-soluble vitamin A, are a promising target for hepatic fibrosis. Herein, a novel theranostic platform based on vitamin A-modified melanin nanoparticles (MNP-VA) is constructed for the integrated diagnosis and treatment of hepatic fibrosis. Thanks to the superior near-infrared (NIR) absorption and thermal stability properties of melanin, the MNP-VA nanoparticles perform therapeutic intervention and real-time monitoring via low-temperature photothermal therapy (LT-PTT) guided by accurate photoacoustic imaging (PA). PA uses the photoacoustic effect for high-resolution, deep-tissue imaging. PTT converts laser light into heat to precisely target and destroy diseased cells with minimal side effects. LT-PTT further reduces damage to healthy tissues while maintaining treatment efficacy. This platform, combined with melanin's antioxidant properties and NIR irradiation, leverages the targeting specificity of vitamin A toward HSCs, significantly reducing collagen deposition and restoring liver architecture in animal models. Overall, our findings indicate that MNP-VA offers a robust strategy for the theranostic management of hepatic fibrosis, addressing the limitations of conventional therapies and paving the way for future clinical translation.