Multifunctional targeted nanoprobe with high NIR-II PAI/MRI performance for precise theranostics of orthotopic early-stage hepatocellular carcinoma

Early diagnosis and effective treatment of hepatocellular carcinoma (HCC) is quite critical for improving patients’ prognosis. The combination of second near-infrared window photoacoustic imaging (NIR-II PAI) and T2-magnetic resonance imaging (T2-MRI) is promising for achieving omnibearing information on HCC diagnosis due to complementary advantages of outstanding optical contrast, high temporospatial resolution and soft-tissue resolution. Thus, the rational design of multifunctional targeted nanoplatform with outstanding performance in dual-modal NIR-II PAI/T2-MRI is particularly valuable for precise diagnosis and image-guiding non-invasive photothermal therapy (PTT) of early-stage HCC. Herein, a versatile targeted organic-inorganic hybrid nanoprobe was synthesized as HCC-specific contrast agent for sensitive and efficient theranostics. The developed multifunctional targeted nanoprobe yielded superior HCC specificity, reliable stability and biocompatibility, high imaging contrast both in NIR-II PAI and T2-MRI, and excellent photothermal conversion efficiency (74.6%). Furthermore, the theranostic efficiency of targeted nanoprobe was systematically investigated using orthotopic early HCC-bearing mice model. The NIR-II PAI exhibited sensitive detection of ultra-small HCCs (diameter less than 1.8 mm), and long-term real-time monitoring of tumors and nanoprobes targeting process in deep tissue. The T2-MRI demonstrated the clear imaging contrast and spatial relationship between micro-HCC and adjacent structures for comprehensive description of tumor. Moreover, upon using targeted nanoprobe, the non-invasively targeted PTT of orthotopic early HCC was carried out under the reliable dual-modal imaging guidance with remarkable anti-tumor efficiency and biosafety. This work provides insight into constructing multifunctional targeted nanoplatform for precise and comprehensive theranostics of early-stage HCC, which would greatly benefit the patients in the era of precision medicine.