Chiral ultrasmall nickel hydroxide nanoparticles enable enantioselective magnetic resonance imaging of hepatocellular carcinoma and lung metastases

Abstract

Hepatocellular carcinoma (HCC) is characterized by high incidence, easy metastasis, and poor prognosis. Magnetic resonance imaging (MRI) offers excellent soft tissue resolution and has clear advantages in the clinical examination of hepatocellular carcinoma. However, commonly used MRI contrast agents have limited imaging effectiveness for small liver cancers and metastatic liver tumors, which constrains the comprehensive clinical treatment of liver cancer. The chemical and biological effects of chiral nanomaterials have garnered widespread attention and present unique advantages in medical diagnostics. In this study, D-/L-Ni(OH)₂ nanoparticles (NPs) modified with aspartic acid were synthesized using an amino acid-mediated one-step transfer method. The chiral selective imaging of D-/L-Ni(OH)₂ NPs was evaluated in and out of primary hepatocellular carcinoma mice through MRI. The results showed that D-/L-Ni(OH)₂ NPs exhibited strong circular dichroism (CD) signals at 370 nm, 560 nm, and 800 nm, and showed high relaxation rates in magnetic resonance imaging (at a 3 T magnetic field, r₁ = 8.2 mM⁻¹ s⁻¹ for D-Ni(OH)₂, and r₁ = 7.1 mM⁻¹ s⁻¹ for L-Ni(OH)₂), higher than the clinically commonly used contrast agent gadopentetate dimeglumine (r₁ = 3.5 mM⁻¹ s⁻¹). In vivo MRI confirmed that chiral Ni(OH)₂ NPs could achieve high-contrast imaging of hepatocellular carcinoma, with D-Ni(OH)₂ NPs showed superior imaging effects, and similar effects were also observed in lung metastases outside the liver. Chiral Ni(OH)₂ NPs exhibited chiral selective MRI of hepatocellular carcinoma and its lung metastases, enhancing the detection sensitivity of MRI for hepatocellular carcinoma and lung metastases, providing a basis for the practical application of chiral nanomaterials in tumor detection during the clinical diagnosis process.