Theranostic Polymeric Micelles for the Diagnosis and Treatment of Hepatocellular Carcinoma.

Theranostics, which combine molecular imaging (diagnostics) and drug delivery (therapeutics) in a single platform, have recently shown great potential in cancer therapy. In this article, a polymeric micelle was designed and prepared for simultaneous magnetic resonance imaging (MRI) and treatment of hepatocellular carcinoma (HCC). Theranostic micelles were assembled using Poly(lactic acid)-poly(ethylene glycol)-poly(L-lysine)-diethylenetriamine pentaacetic acid (PLA-PEG-PLL-DTPA) and PLA-PEG-PLL-Biotin. The HCC therapeutic paclitaxel (PTX) was encapsulated in the cores and Gd ions for imaging were chelated to the DTPA moieties. Biotinylated alpha-fetoprotein (AFP) antibodies were linked to the micelle surface by a biotin-avidin reaction to form targeted Gd/PTX-loaded micelles (TGPM). TGPM were of spherical or ellipsoidal shape with uniform particle size distribution (147.50 ± 4.71 nm), positive zeta potential (24.45 ± 1.04 mV), and high encapsulation efficiency (88.76 ± 1.64%) and drug loading (1.59 ± 0.06%). The cytotoxicity of TGPM in HepG2 cells was superior to that of Taxol or Gd/PTX-loaded micelles (GPM). In MRI tests in vitro, the T1 relaxivity of TGPM was 21.589 mM(-1) s(-1), 4.4 times higher than Magnevist (r1 = 4.8 mM(-1) s(-1)). In H22 tumor-bearing mice, TGPM significantly increased tumor imaging intensity (more than 3 times) and prolonged imaging time (from 1 to 6 h) compared to Magnevist. In vivo, TGPM exhibited higher anti-tumor efficiency than Taxol and GPM. These results indicate that TGPM has great potential in HCC theranostics.