Iron oxide nanoflowers encapsulated in thermosensitive fluorescent liposomes for hyperthermia treatment of lung adenocarcinoma.

Magnetic hyperthermia (MHT) is in the spotlight of nanomedical research for the treatment of cancer employing magnetic iron oxide nanoparticles and their intrinsic capability for heat dissipation under an alternating magnetic field (AMF). Herein we focus on the synthesis of iron oxide nanoflowers (Nfs) of different sizes (15 and 35 nm) and coatings (bare, citrate, and Rhodamine B) while comparing their physicochemical and magnetothermal properties. We encapsulated colloidally stable citrate coated Nfs, of both sizes, in thermosensitive liposomes via extrusion, and RhB was loaded in the lipid bilayer. All formulations proved hemocompatible and cytocompatible. We found that 35 nm Nfs, at lower concentrations than 15 nm Nfs, served better as nanoheaters for magnetic hyperthermia applications. In vitro, magnetic hyperthermia results showed promising therapeutic and imaging potential for RhB loaded magnetoliposomes containing 35 nm Nfs against LLC and CULA cell lines of lung adenocarcinoma.

Multisensitive Polymeric Nanocontainers as Drug Delivery Systems: Biological Evaluation.

This chapter focuses on the in vitro biological evaluation of multisensitive nanocontainers as drug delivery systems for cancer treatment. Cancer tissues possess some unique characteristics such as increased temperature due to inflammation, thermal vulnerability (40-45 °C), low cellular pH, and redox instabilities. The employment of polymers bearing pH, thermo, and/or redox sensitivities in the synthesis of hollow polymeric nanostructures has led to the formulation of a variety of drug delivery vehicles that are capable of targeted delivery and trigger specific drug release. The cavity in the structure allows for the encapsulation of anticancer drugs as well as other moieties with anticancer activity, like iron oxide magnetic nanoparticles. The drug loading and release capability of the nanocontainers is evaluated prior to biological studies in order to determine the concentration of the drug in the structure. The in vitro assessment includes cytotoxicity studies, quantitatively through the colorimetric MTT assay as well as qualitatively via the scratch-wound healing assay, on both cancer and healthy cell lines. The cellular localization of the studied drug-loaded and unloaded nanocontainers is determined through confocal fluorescence microscopy.

Magnetic fluid hyperthermia simulations in evaluation of SAR calculation methods.

PURPOSE: The purpose of this study is to employ magnetic fluid hyperthermia simulations in the precise computation of Specific Absorption Rate functions -SAR(T)-, and in the evaluation of the predictive capacity of different SAR calculation methods. METHODS: Magnetic fluid hyperthermia experiments were carried out using magnetite-based nanofluids. The respective SAR values were estimated through four different calculation methods including the initial slope method, the Box-Lucas method, the corrected slope method and the incremental analysis method (INCAM). A novel numerical model combining the heat transfer equations and the Navier-Stokes equations was developed to reproduce the experimental heating process. To address variations in heating efficiency with temperature, the expression of the power dissipation as a Gaussian function of temperature was introduced and the Levenberg-Marquardt optimization algorithm was employed to compute the function parameters and determine the function's effective branch within each measurement's temperature range. The power dissipation function was then reduced to the respective SAR function. RESULTS: The INCAM exhibited the lowest relative errors ranging between 0.62 and 15.03% with respect to the simulations. SAR(T) functions exhibited significant variations, up to 45%, within the MFH-relevant temperature range. CONCLUSIONS: The examined calculation methods are not suitable to accurately quantify the heating efficiency of a magnetic fluid. Numerical models can be exploited to effectively compute SAR(T) and contribute to the development of robust hyperthermia treatment planning applications.

(99m)Tc-labeled aminosilane-coated iron oxide nanoparticles for molecular imaging of ανß3-mediated tumor expression and feasibility for hyperthermia treatment.

HYPOTHESIS: Dual-modality imaging agents, such as radiolabeled iron oxide nanoparticles (IO-NPs), are promising candidates for cancer diagnosis and therapy. We developed and evaluated aminosilane coated Fe3O4 (10±2nm) as a tumor imaging agent in nuclear medicine through 3-aminopropyltriethoxysilane (APTES) functionalization. We evaluated this multimeric system of targeted (99m)Tc-labeled nanoparticles (NPs) conjugated with a new RGD derivate (cRGDfK-Orn3-CGG), characterized as NPs-RGD as a potential thermal therapy delivery vehicle. EXPERIMENTS: Transmission Electron Microscopy (TEM) and spectroscopy techniques were used to characterize the IO-NPs indicating their functionalization with peptides. Radiolabeled IO-NPs (targeted, non-targeted) were evaluated with regard to their radiochemical, radiobiological and imaging characteristics. In vivo studies were performed in normal and ανß3-positive tumor (U87MG glioblastoma) bearing mice. We also demonstrated that this system could reach ablative temperatures in vivo. FINDINGS: Both radiolabeled IO-NPs were obtained in high radiochemical yield (>98%) and proved stable in vitro. The in vivo studies for both IO-NPs have shown significant liver and spleen uptake at all examined time points in normal and U87MG glioblastoma tumor-bearing mice, due to their colloidal nature. We have confirmed through in vivo biodistribution studies that the non-targeted (99m)Tc-NPs poorly internalized in the tumor, while the targeted (99m)Tc-NPs-RGD, present 9-fold higher tumor accumulation at 1h p.i. Accumulation of both IO-NPs in other organs was negligible. Blocking experiments indicated target specificity for integrin receptors in U87MG glioblastoma cells. The preliminary in vivo study of applied alternating magnetic field showed that the induced hyperthermia is feasible due to the aid of IO-NPs.