Targeted temperature sensitive magnetic liposomes for thermo-chemotherapy.
ABSTRACT We describe folate receptor targeted thermosensitive magnetic liposomes, which are designed to combine features of biological and physical (magnetic) drug targeting for use in magnetic hyperthermia-triggered drug release. The optimized liposome formulation DPPC:cholesterol:DSPE-PEG(2000):DSPE-PEG(2000)-Folate at 80:20:4.5:0.5 molar ratio showed calcein release of about 70% both in PBS and in 50% FBS (fetal bovine serum) at 43 degrees C and less than 5% release at 37 degrees C following 1h incubation. Folate-targeted doxorubicin-containing magnetic liposomes of the above lipid composition (MagFolDox) showed encapsulation efficiencies of about 85% and 24% for doxorubicin and magnetic nanoparticles (mean crystallite size 10nm), respectively. This magnetic formulation displayed the desired temperature sensitivity with 52% doxorubicin release in 50% fetal bovine serum (FBS) following 1h incubation at 43 degrees C. MagFolDox, when physically targeted to tumor cells in culture by a permanent magnetic field yielded a substantial increase in cellular uptake of doxorubicin as compared to Caelyx (a commercially available liposomal doxorubicin preparation), non-magnetic folate-targeted liposomes (FolDox) and free doxorubicin in folate receptor expressing tumor cell lines (KB and HeLa cells). This resulted in a parallel increase in cytotoxicity over Caelyx and FolDox. Magnetic hyperthermia at 42.5 degrees C and 43.5 degrees C synergistically increased the cytotoxicity of MagFolDox. The results suggest that an integrated concept of biological and physical drug targeting, triggered drug release and hyperthermia based on magnetic field influence can be used advantageously for thermo-chemotherapy of cancers.
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ABSTRACT: Engineered nanoparticles (NPs) are widely used in many sectors, such as food, medicine, military, and sport, but their unique characteristics may cause deleterious health effects. Close attention is being paid to metal NP genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying mechanisms remain to be elucidated. In this review, we address some metal and metal oxide NPs of interest and current genotoxicity tests in vitro and in vivo. Metal NPs can cause DNA damage such as chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. We also discuss several parameters that may affect genotoxic response, including physicochemical properties, widely used assays/end point tests, and experimental conditions. Although potential biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent findings in the literature render results inconclusive due to a variety of factors. Advantages and limitations related to different methods for investigating genotoxicity are described, and future directions and recommendations for better understanding genotoxic potential are addressed.International Journal of Nanomedicine 01/2014; 9(Suppl 2):271-286. DOI:10.2147/IJN.S57918 · 4.20 Impact Factor
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ABSTRACT: Superparamagnetic iron oxide nanoparticles are used in a rapidly expanding number of research and practical applications in biotechnology and biomedicine. We highlight how recent developments in iron oxide nanoparticle design and understanding of nanoparticle membrane interactions have led to applications in magnetically triggered, liposome delivery vehicles with controlled structure. Nanoscale vesicles actuated by incorporated nanoparticles allow for controlling location and timing of compound release, which enables e.g. use of more potent drugs in drug delivery as the interaction with the right target is ensured. This review emphasizes recent results on the connection between nanoparticle design, vesicle assembly and the stability and release properties of the vesicles. While focused on lipid vesicles magnetically actuated through iron oxide nanoparticles, these insights are of general interest for the design of capsule and cell delivery systems for biotechnology controlled by nanoparticles.New Biotechnology 12/2014; DOI:10.1016/j.nbt.2014.12.002 · 2.11 Impact Factor
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ABSTRACT: The aim of this work was to construct carboxymethyl dextran (CMD)-coated magnetoliposomes (MLs), another stealth MLs alternative to PEGylated MLs, for theranostic application. Particularly, the on-demand release of CMD-MLs under low-frequency alternating magnetic field (LF-AMF) was studied. We found that as-prepared MLs exhibited good stability and high drug loading ability for doxorubicin (DOX). Cytotoxicity assay against human neuroblastoma SH-SY5Y cells showed that the DOX-loaded CMD-MLs were less toxic than free DOX due to the sustained release of DOX. However, the release of DOX-loaded CMD-MLs was enhanced by low-frequency alternating magnetic field without hyperthermia generation. The MLs also acted as an efficient T2-weighted contrast agent during in vitro MRI measurements. The above results provide useful information on in vivo diagnostic/therapeutic efficacy of DOX-loaded CMD-MLs for some cancers, such as brain cancers. Copyright © 2014 Elsevier Ltd. All rights reserved.Carbohydrate Polymers 03/2015; 118C:209-217. DOI:10.1016/j.carbpol.2014.10.076 · 3.92 Impact Factor