Regul Toxicol Pharmacol
November 2024
The neurobehavioral assessment of N,N-bis(2-mercapatoethly)-N',N'-diethylenediamine (BMEDA), which can form a chelate with rhenium-188 (Re) to produce the Re-BMEDA-liposome, was evaluated. The purpose of this study was to evaluate the potential neurobehavioral changes by using the functional observational battery observation procedures when intravenous injection of BMEDA to Sprague-Dawley rats. Rats were administered BMEDA at dose levels of 1, 2, and 5 mg/kg.
View Article and Find Full Text PDFNanoliposomes are one of the leading potential nano drug delivery systems capable of targeting chemotherapeutics to tumor sites because of their passive nano-targeting capability through the enhanced permeability and retention (EPR) effect for cancer patients. Recent advances in nano-delivery systems have inspired the development of a wide range of nanotargeted materials and strategies for applications in preclinical and clinical usage in the cancer field. Nanotargeted Re-liposome is a unique internal passive radiotheranostic agent for nuclear imaging and radiotherapeutic applications in various types of cancer.
View Article and Find Full Text PDFEpidermal growth factor receptor (EGFR) specific therapeutics is of great importance in cancer treatment. Fcy-hEGF fusion protein, composed of yeast cytosine deaminase (Fcy) and human EGF (hEGF), is capable of binding to EGFR and enzymatically convert 5-fluorocytosine (5-FC) to 1000-fold toxic 5-fluorocuracil (5-FU), thereby inhibiting the growth of EGFR-expressing tumor cells. To develop EGFR-specific therapy, Re-liposome-Fcy-hEGF was constructed by insertion of Fcy-hEGF fusion protein onto the surface of liposomes encapsulating of Re.
View Article and Find Full Text PDFNanotargeted liposomes may be modified with targeting peptide on the surface of a prepared liposome to endow specificity and elevate targeting efficiency. The aim of this study was to develop a radioactive targeted nanoparticle, the In-cyclic RGDfK-liposome, and its advantage of recognizing the αβ3 integrin was examined. The cyclic RGDfK modified liposomes were demonstrated the ability to bind the αβ3 integrin expressed on the surface of human melanoma cell in vitro and in vivo.
View Article and Find Full Text PDFBackground: Liposomes are drug nano-carriers that are capable of targeting therapeutics to tumor sites because of enhanced permeability retention (EPR). In several preclinical studies with various tumor-bearing mice models, Re-liposome that has been developed by the Institute of Nuclear Energy Research (INER) demonstrates favorable in vivo tumor targeting, biodistribution, pharmacokinetics, and dosimetry. It inhibits the growth of tumors, increased survival, demonstrates good synergistic combination, and was safe to use.
View Article and Find Full Text PDFCell Death Discov
October 2018
Human head and neck squamous cell carcinoma (HNSCC) is usually treated with chemoradiotherapy, but the therapeutic efficacy could be hampered by intrinsic radioresistance and early relapse. Repeated administrations of rhenium-188 (Re)-conjugated radiopharmaceutical has been reported to escalate the radiation doses for better control of advanced human cancers. Here we found that high dosage of Re-liposome, the liposome-encapsulated Re nanoparticles exhibited significant killing effects on HNSCC FaDu cells and SAS cells but not on OECM-1 cells.
View Article and Find Full Text PDFDespite standard treatment, about 70% of ovarian cancer will recur. Cancer stem cells (CSCs) have been implicated in the drug-resistance mechanism. Several drug resistance mechanisms have been proposed, and among these, autophagy plays a crucial role for the maintenance and tumorigenicity of CSCs.
View Article and Find Full Text PDFPurpose: Liver cancer is the second most common cause of death worldwide. This study was to investigate the SPECT/CT, ultrasound, biodistribution and therapeutic evaluation of Re-human serum albumin microspheres (Re-HSAM) in the GP7TB orthotopic hepatoma rat model.
Materials And Methods: HSAM was labeled with Re by using a home-made kit and microwave system.
Human head and neck squamous cell carcinoma (HNSCC) is usually treated by surgical resection with adjuvant radio-chemotherapy. In this study, we examined whether the radiopharmaceutical 188Re-liposome could suppress the growth of HNSCC followed by an investigation of molecular mechanisms. The orthotopic HNSCC tumor model was established by human hypopharyngeal FaDu carcinoma cells harboring multiple reporter genes.
View Article and Find Full Text PDFIt is more challenging to design peptide drugs than small molecules through molecular docking and in silico analysis. Here, we developed a structure-based approach with various computational and analytical techniques to optimize cancer-targeting peptides for molecular imaging and therapy. We first utilized a peptide-binding protein database to identify GRP78, a specific cancer cell-surface marker, as a target protein for the lead, L-peptide.
View Article and Find Full Text PDFBackground And Purpose: Cancer stem cells exhibit distinctive cellular metabolism compared with the more differentiated counterparts or normal cells. We aimed to investigate the impact of a novel radionuclide anti-cancer agent (188)Re-Liposome on stemness markers' expression and cellular metabolism in an ovarian cancer model.
Material And Methods: A 2×2 factorial experiment was designed in which factor 1 represented the drug treatment comparing (188)Re-BMEDA, a free form of (188)Re, with (188)Re-Liposome, a nanoparticle-encapsulated form of (188)Re.
Background/aim: We aimed to construct epidermal growth factor receptor (EGFR)-targeting cetuximab-immunoliposomes (IL-C225) for targeted delivery of doxorubicin and rhenium-188 (Re-188) to EGFR(+) cancer cells.
Materials And Methods: Synthesized IL-C225 was analyzed by dynamic light scattering, transmission electron microscopy, and matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy. Cell binding and internalization were examined using doxorubicin-loaded IL-C225 (DXR-IL-C225) with confocal microscopy.
Background/aim: Interferon-α (IFN-α) is produced to act locally and transiently with a relatively short circulation half-life in vivo. Hybridization of IFN-α with human immunoglobulin Fc, renamed as IFN-α-Fc, may overcome this limitation. In the present study, (131)I-IFN-α-Fc and (131)I-IFN-α were compared in the aspects of stability, pharmacokinetics, tissue distribution and molecular imaging quality in an animal model.
View Article and Find Full Text PDFExternal beam radiotherapy (EBRT) treats gross tumors and local microscopic diseases. Radionuclide therapy by radioisotopes can eradicate tumors systemically. Rhenium 188 ((188)Re)-liposome, a nanoparticle undergoing clinical trials, emits gamma rays for imaging validation and beta rays for therapy, with biodistribution profiles preferential to tumors.
View Article and Find Full Text PDFObjective: The present study relates to a method for preparing 188Re-labeled human serum albumin microspheres (HSAM) by 188Re(I)-tricarbonyl ion(188Re(OH2)3(CO)3)+). This radioactive particle can be subjected to radioembolization for liver tumor.
Methods: The particle sizes and conformations of HSA microspheres were analyzed by Particle sizes-Malvern mastersizer and Scanning Electron Microscope (SEM).
Purpose: In this study, the (188)Re-labeled PEGylated nanoliposome ((188)Re-liposome) was prepared and evaluated as a therapeutic agent for glioma.
Materials And Methods: The reporter cell line, F98(luc) was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of (188)Re-liposome with varying dosages before the treatment study.
Unlabelled: Non-small cell lung cancer (NSCLC) is a highly morbid and mortal cancer type that is difficult to eradicate using conventional chemotherapy and radiotherapy. Little is known about whether radionuclide-based pharmaceuticals can be used for treating NSCLC. Here we embedded the therapeutic radionuclide (188)Re in PEGylated (PEG is polyethylene glycol) liposomes and investigated the biodistribution, pharmacokinetics, and therapeutic efficacy of this nanoradiopharmaceutical on NSCLC using a xenograft lung tumor model and the reporter gene imaging techniques.
View Article and Find Full Text PDFLiposome in delivering radionuclide for cancer therapy has been expansively studied; however, liposome itself can be deliberately entrapped and destroyed by the reticuloendothelial system, causing an insufficiency of the drug delivery, which in turn would restrict the effectiveness of the drug. In this study, mice with subcutaneous implantation of C26 murine colon cancer received an experimental treatment regimen in which mice took delivery of PEGylated liposomal doxorubicin (LipoDox) first, after a three-day interval, of Rhenium-188 encapsulated into PEGylated liposome ((188)Re-Liposome) subsequently and by which suppressed the functioning of reticuloendothelial system for the short term. The data showed that based upon the biodistribution assay and the evaluation of the therapeutic efficacy, (188)Re-Liposome was more sufficiently delivered to tumor sites in mice with this treatment regimen than mice without the regimen, and that cancer mortalities in mice with the treatment regimen were much lower than the mortalities in mice without the regimen.
View Article and Find Full Text PDFRhenium-188 (Re) displays abundant intermediate energy β emission and possesses a physical half-life of 16.9 h. Sorafenib is an orally available multikinase inhibitor that targets Raf kinases and vascular endothelial growth factor receptors (VEGFRs).
View Article and Find Full Text PDFRegul Toxicol Pharmacol
July 2014
N,N-Bis(2-mercaptoethyl)-N',N'-diethylenediamine (BMEDA) is used in the preparation of the (188)Re-BMEDA-liposome as a chelator to deliver rhenium 188 into liposomes. Although the safety of the (188)Re-BMEDA-liposome had been established, the use of BMEDA in preparing the liposome is of interest; however, an assessment of its safety is warranted. In this present work, we report on the acute toxicity study of BMEDA in beagles to identify doses causing no adverse effect and doses causing life-threatening toxicity.
View Article and Find Full Text PDFUnlabelled: Abstract Purpose: The radioprotective effects of Antrodia cinnamomea (AC) were investigated for understanding the potential usefulness of AC as an adjunct treatment for reducing radiation side-effects.
Materials And Methods: In this study, we determined the ability of AC extracts (AC539) to reduce radiation side-effects by analyzing cellular viability in normal mouse spleen immune cells and human cancer cells with different radiosensitivity. We further detected the effect of AC on radiation-induced changes in cytokine- and inflammatory-related gene expressions.
The pharmacokinetics of N,N-bis(2-mercapatoethly)-N',N'-diethylenediamine (BMEDA), a molecule that can form a chelate with rhenium-188 (188Re) to produce the 188Re-BMEDA-liposomes, was studied. In this work, beagles received a single injection of BMEDA, at doses of 1, 2, or 5 mg/kg; the concentration of BMEDA in the beagles' plasma was then analyzed and determined by liquid chromatography-mass spectrometry/mass spectrometry. Based on the pharmacokinetic parameters of BMEDA, we found that male and female animals shared similar patterns indicating that the pharmacokinetics of BMEDA is independent of gender differences.
View Article and Find Full Text PDFThe coupling of specific antibodies to imaging agents often improves imaging specificity. However, free amine groups designed for the coupling can cause nonspecific binding of the imaging agents. We report here development of a nanocarrier, MnMEIO-silane-NH2-mPEG nanoparticles (NPs), consisting of a manganese-doped iron oxide nanoparticle core (MnMEIO), a copolymer shell of silane and amine-functionalized poly(ethylene glycol) (silane-EA-mPEG).
View Article and Find Full Text PDFIn this study, lactoferrin-conjugated PEGylated liposomes (PL), a potential drug carrier for brain delivery, was loaded with radioisotope complex, 99mTc labeled N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (99mTc-BMEDA) for in vitro and in vivo evaluations. The hydrophilicity of liposomes was enhanced by PEGylation which was not an ideal brain delivery system for crossing the blood brain barrier (BBB). With the modification of a brain-targeting ligand, lactoferrin (Lf), the PEGylated liposome (PL) might become a potential brain delivery vehicle.
View Article and Find Full Text PDFNanoliposomes are good drug delivery systems that allow the encapsulation of drugs into vesicles for their delivery. The objective of this study is to investigate the therapeutic efficacy of a new radio-therapeutics of (188)Re-labeled pegylated liposome in a C26 murine colon carcinoma solid tumor model. The safety of (188)Re-liposome was evaluated before radiotherapy treatment.
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