ABSTRACT
PURPOSE: In this study, we synthesized hyaluronic acid-conjugated gadolinium (HA-diethylene triamine pentaacetic acid (DTPA)-Gd) and evaluated as hepatocyte-specific magnetic resonance imaging (MRI) contrast agent for the diagnosis of hepatic metastasis. PROCEDURES: We conducted Fourier transform (FT)-IR analysis to determine the conjugation of HA and DTPA and performed cell viability assays using NIH3T3 and FL83B cell lines. We also conducted T1-weighted MRI of HA-DTPA-Gd and gadoxetic acid to compare the paramagnetic properties of both. RESULTS: HA-DTPA-Gd had a higher efficiency in liver MRI compared with the commercially available liver-specific contrast agent (p < 0.001). HA-DTPA-Gd, which possessed a higher T1 relaxivity, showed excellent capability for the diagnosis of hepatic metastasis through an in vivo MRI study in comparison with gadoxetic acid (p < 0.001). CONCLUSION: Based on this study, we believe that HA-DTPA-Gd has promising potential for use as a contrast agent for liver MRI of hepatic metastases.
Subject(s)
Contrast Media/chemistry , Gadolinium/chemistry , Hyaluronic Acid/chemistry , Liver/metabolism , Magnetic Resonance Imaging/methods , Animals , Contrast Media/pharmacokinetics , Gadolinium/pharmacokinetics , Hepatocytes/metabolism , Hyaluronic Acid/pharmacokinetics , Liver Neoplasms, Experimental/metabolism , Mice , Mice, Inbred BALB C , NIH 3T3 CellsABSTRACT
In this study, we prepared iron oxide nanoparticle and doxorubicin-loaded multifunctional nano-carrier (IONP/DOX-MFNC), capable of simultaneous cancer targeting via a herceptin monoclonal antibody, controlled anticancer drug delivery, as well as imaging modalities of magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging. IONP and DOX were efficiently loaded into the nano-carrier, and a desirable pH-responsive release of DOX was achieved by MFNC. The nano-carrier showed much higher cellular uptake and stronger cytotoxicity to HER2 overexpressed SK-BR-3 (human breast cancer cells) than MCF-7, a negative control cell, suggesting specific cancer targeting via HER2 receptor. In an in vivo tumor xenograft model, IONP/DOX-MFNC showed higher tumor uptake and significantly enhanced tumor regression than the nano-carrier without the antibody. Thus, DOX-loaded, multi-functional nano-carrier with HER2 antibody was effective for both imaging and therapy, showing the potential for early stage cancer diagnosis and simultaneous therapy. FROM THE CLINICAL EDITOR: In this study, efficacy -both for imaging and treatment - was demonstrated on a doxorubicin and iron oxide nanoparticle loaded multifunctional nano-carrier with HER2 antibody to show the potential for early stage cancer diagnosis and simultaneous therapy.
Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Breast Neoplasms/drug therapy , Doxorubicin/administration & dosage , Drug Delivery Systems , Ferric Compounds/administration & dosage , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal, Humanized/chemistry , Antineoplastic Agents , Breast Neoplasms/pathology , Contrast Media , Doxorubicin/chemistry , Female , Ferric Compounds/chemistry , Humans , MCF-7 Cells , Magnetic Resonance Imaging , Metal Nanoparticles/administration & dosage , Metal Nanoparticles/chemistry , Mice , Receptor, ErbB-2/immunology , Receptor, ErbB-2/therapeutic use , Trastuzumab , Xenograft Model Antitumor AssaysABSTRACT
To achieve a sufficient targeting efficiency and prolonged half-life in-vivo, the physicochemical parameters including size and surface chemistry of therapeutic and imaging agents should be controlled. In this study, we prepared an iron oxide nanoparticle (IONP)-loaded, functional nano-carrier with different loading contents to modulate the mechanical properties of the system, and compared the characteristics of tumor targeting and imaging in terms of loading contents of IONP. As a functional nano-carrier, chitosan-conjugated, Pluronic-based nano-carrier with useful properties such as long blood circulation, good tumor targeting, and easy loading of macromolecules was used. IONPs were efficiently encapsulated into the nano-carrier (high loading efficiency over 95%) and the mechanical properties of the IONP-loaded nano-carrier were controlled by varying the loading amount of IONP. The IONP-loaded nano-carrier with the higher loading content of IONP (40 wt.%) was significantly more rigid (over 2×) than those with lower loading contents of IONP (5 and 15 wt.%). Although the nano-carrier with the higher loading content of IONP showed more enhanced MR contrast effect with higher T(2) relaxivity and higher intracellular uptake in vitro, characteristics of in-vivo tumor targeting and MR cancer imaging were not good compared to that of the nano-carrrier with the lower loading contents of IONP. Since different loading contents did not affect other characteristics of the system (size, surface chemistry, and surface charge), the present result suggests that the mechanical properties (strength/flexibility) of nano-systems are also important factors to be controlled for targeted delivery and imaging.
Subject(s)
Contrast Media/chemistry , Drug Carriers/chemistry , Ferric Compounds/chemistry , Metal Nanoparticles/chemistry , Animals , Cell Line, Tumor , Cell Survival/drug effects , Chitosan/chemistry , Drug Carriers/therapeutic use , Excipients/chemistry , Ferric Compounds/therapeutic use , Magnetic Resonance Imaging , Male , Metal Nanoparticles/therapeutic use , Mice , Mice, Nude , NIH 3T3 Cells , Neoplasms/diagnosis , Neoplasms/drug therapy , Poloxamer/chemistry , Surface-Active Agents/chemistryABSTRACT
Positively charged superparamagnetic iron oxide nanoparticle (SPION)-loaded polymersome was prepared in order to deliver genes to the target sites, which was monitored by magnetic resonance imaging (MRI), concomitantly. The transfection efficiency in vitro was tested by treating CT-26 colon cancer cell line with luciferase-expressing plasmids/SPION complex. MRI was also used to check the detectability of SPION in vitro and in vivo. SPION-loaded polymersome, carrying genetic materials, was delivered and then accumulated at the tumor site of the murine colon cancer xenograft model after intravenous injection, possibly through a passive targeting mechanism. Clinical MRI monitored this accumulation. This result indicates that the SPION-loaded polymersomecan be applied to MR image-guided gene therapy.
