Recent advances in zinc ferrite (ZnFe2O4) based nanostructures for magnetic hyperthermia applications.

Spinel ferrite-based magnetic nanomaterials have been investigated for numerous biomedical applications, including targeted drug delivery, magnetic hyperthermia therapy (MHT), magnetic resonance imaging (MRI), and biosensors, among others. Recent studies have found that zinc ferrite-based nanomaterials are favorable candidates for cancer theranostics, particularly for magnetic hyperthermia applications. Zinc ferrite exhibits excellent biocompatibility, minimal toxicity, and more importantly, exciting magnetic properties. In addition, these materials demonstrate a Curie temperature much lower than other transition metal ferrites. By regulating synthesis protocols and/or introducing suitable dopants, the Curie temperature of zinc ferrite-based nanosystems can be tailored to the MHT therapeutic window, i.e., 43-46 °C, a range which is highly beneficial for clinical hyperthermia applications. Furthermore, zinc ferrite-based nanostructures have been extensively used in successful pre-clinical trials on mice models focusing on the synergistic killing of cancer cells involving magnetic hyperthermia and chemotherapy. This review provides a systematic and comprehensive understanding of the recent developments of zinc ferrite-based nanomaterials, including doped particles, shape-modified structures, and composites for magnetic hyperthermia applications. In addition, future research prospects involving pure ZnFe2O4 and its derivative nanostructures have also been proposed.

Rare-Earth Doped Iron Oxide Nanostructures for Cancer Theranostics: Magnetic Hyperthermia and Magnetic Resonance Imaging.

Superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively investigated during the last couple of decades because of their potential applications across various disciplines ranging from spintronics to nanotheranostics. However, pure iron oxide nanoparticles cannot meet the requirement for practical applications. Doping is considered as one of the most prominent and simplest techniques to achieve optimized multifunctional properties in nanomaterials. Doped iron oxides, particularly, rare-earth (RE) doped nanostructures have shown much-improved performance for a wide range of biomedical applications, including magnetic hyperthermia and magnetic resonance imaging (MRI), compared to pure iron oxide. Extensive investigations have revealed that bigger-sized RE ions possessing high magnetic moment and strong spin-orbit coupling can serve as promising dopants to significantly regulate the properties of iron oxides for advanced biomedical applications. This review provides a detailed investigation on the role of RE ions as primary dopants for engineering the structural and magnetic properties of Fe3 O4 nanoparticles to carefully introspect and correlate their impact on cancer theranostics with a special focus on magnetic hyperthermia and MRI. In addition, prospects for achieving high-performance magnetic hyperthermia and MRI are thoroughly discussed. Finally, suggestions on future work in these two areas are also proposed.

Secretion induces cell pH dynamics impacting assembly-disassembly of the fusion protein complex: A combined fluorescence and atomic force microscopy study.

A wide range of cellular activities including protein folding and cell secretion, such as neurotransmission or insulin release, are all governed by intracellular pH homeostasis, underscoring the importance of pH on critical life processes. Nano- scale pH measurements of cells and biomolecules therefore hold great promise in understanding a plethora of cellular functions, in addition to disease detection and therapy. In the current study, a novel approach using cadmium telluride quantum dots (CdTeQDs) as pH sensors, combined with fluorescent imaging, spectrofluorimetry, atomic force microscopy (AFM), and Western blot analysis, enabled the study of intracellular pH dynamics at 1 milli-pH sensitivity and 80nm pixel resolution, during insulin secretion. Additionally, the pH-dependent interaction between membrane fusion proteins, also called the soluble N-ethylmaleimide-sensitive factor activating protein receptor (SNARE), was determined. Glucose stimulation of CdTeQD-loaded insulin secreting Min-6 mouse insulinoma cell line demonstrated the initial (5-6min) intracellular acidification reflected as a loss in QD fluorescence, followed by alkalization and a return to resting pH in 10min. Analysis of the SNARE complex in insulin secreting Min-6 cells demonstrated an initial gain followed by loss of complexed SNAREs in 10min. Stabilization of the SNARE complex at low intracellular pH is further supported by results from studies utilizing both native and AFM measurements of liposome-reconstituted recombinant neuronal SNAREs, providing a molecular understanding of the role of pH during cell secretion.

Nanothermometry Measure of Muscle Efficiency.

Despite recent advances in thermometry, determination of temperature at the nanometer scale in single molecules to live cells remains a challenge that holds great promise in disease detection among others. In the present study, we use a new approach to nanometer scale thermometry with a spatial and thermal resolution of 80 nm and 1 mK respectively, by directly associating 2 nm cadmium telluride quantum dots (CdTe QDs) to the subject under study. The 2 nm CdTe QDs physically adhered to bovine cardiac and rabbit skeletal muscle myosin, enabling the determination of heat released when ATP is hydrolyzed by both myosin motors. Greater heat loss reflects less work performed by the motor, hence decreased efficiency. Surprisingly, we found rabbit skeletal myosin to be more efficient than bovine cardiac. We have further extended this approach to demonstrate the gain in efficiency of Drosophila melanogaster skeletal muscle overexpressing the PGC-1α homologue spargel, a known mediator of improved exercise performance in humans. Our results establish a novel approach to determine muscle efficiency with promise for early diagnosis and treatment of various metabolic disorders including cancer.

Functionalized nanoparticles enable tracking the rapid entry and release of doxorubicin in human pancreatic cancer cells.

Efficient drug delivery is critical to therapy. Using electron microscopy, X-ray, and light microscopy, we have characterized functionalized superparamagnetic iron oxide (SPIO) nanoparticles, and determined their ability for rapid entry and release of the cancer drug doxorubicin in human pancreatic cancer cells. Dextran-coated SPIO nanoparticle ferrofluid, functionalized with the red-autofluorescing doxorubicin and the green-fluorescent dye fluorescein isothiocyanate as a reporter, enables tracking the intracellular nanoparticle transport and drug release. This engineered nanoparticle enables a >20 fold rapid entry and release of the drug in human pancreatic cancer cells, holding therapeutic potential as an advanced drug delivery and imaging platform. The low extracellular pH of most tumors precluding the entry of a number of weakly basic drugs such as doxorubicin, conferring drug resistance, can now be overcome.