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Theranostic Polymeric Micelles for the Diagnosis and Treatment of Hepatocellular Carcinoma

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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.
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Keywords: ALPHA-FETOPROTEIN; MAGNETIC RESONANCE IMAGING; PACLITAXEL; POLYMERIC MICELLES; THERANOSTICS

Document Type: Research Article

Publication date: April 1, 2015

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  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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