title: Theranostic Polymeric Micelles for the Diagnosis and Treatment of Hepatocellular Carcinoma.
abstract: 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.
authors: Yongjun
authors: Y
authors: Liu
authors: Junsheng
authors: J
authors: Li
authors: Fengxi
authors: F
authors: Liu
authors: Lixia
authors: L
authors: Feng
authors: Dexin
authors: D
authors: Yu
authors: Na
authors: N
authors: Zhang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D001360:Avidin / Q000737:chemistry; D001710:Biotin / Q000737:chemistry; D019921:Biotinylation; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000628:therapy*; D006046:Gold / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D007773:Lactates / Q000737:chemistry; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D053768:Metal Nanoparticles / Q000737:chemistry; D051379:Mice; D008823:Micelles; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry; D004369:Pentetic Acid / Q000737:chemistry; D010789:Phototherapy / Q000379:methods; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D026082:Singlet Oxygen / Q000737:chemistry; D000509:alpha-Fetoproteins / Q000737:chemistry
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D007773:Lactates; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D000509:alpha-Fetoproteins; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; C469934:poly(lactic acid)-poly(ethylene glycol)-biotin; C088513:poly(lactic acid-ethylene glycol); D001360:Avidin; D026082:Singlet Oxygen; D011092:Polyethylene Glycols; D001710:Biotin; D006046:Gold; D004369:Pentetic Acid; D017239:Paclitaxel