ABSTRACT
While investigating the possible synergistic effect of the conventional anticancer therapies, which, taken individually, are often ineffective against critical tumors, such as central nervous system (CNS) ones, the design of a theranostic nanovector able to carry and deliver chemotherapy drugs and magnetic hyperthermic agents to the target radiosensitizers (oxygen) was pursued. Alongside the original formulation of polymeric biodegradable oxygen-loaded nanostructures, their properties were fine-tuned to optimize their ability to conjugate therapeutic doses of drugs (doxorubicin) or antitumoral natural substances (curcumin). Oxygen-loaded nanostructures (diameter = 251 ± 13 nm, ζ potential = -29 ± 5 mV) were finally decorated with superparamagnetic iron oxide nanoparticles (SPIONs, diameter = 18 ± 3 nm, ζ potential = 14 ± 4 mV), producing stable, effective and non-agglomerating magnetic nanovectors (diameter = 279 ± 17 nm, ζ potential = -18 ± 7 mV), which could potentially target the tumoral tissues under magnetic driving and are monitorable either by US or MRI imaging.
Subject(s)
Antibiotics, Antineoplastic/pharmacology , Chitosan/chemistry , Hyperthermia, Induced/methods , Magnetite Nanoparticles/chemistry , Radiation-Sensitizing Agents/pharmacology , Theranostic Nanomedicine/methods , Antibiotics, Antineoplastic/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/radiation effects , Contrast Media/chemical synthesis , Contrast Media/pharmacology , Curcumin/chemistry , Curcumin/pharmacology , Dextran Sulfate/chemistry , Doxorubicin/chemistry , Doxorubicin/pharmacology , Drug Compounding/methods , Humans , Kinetics , Magnetite Nanoparticles/ultrastructure , Oxygen/chemistry , Oxygen/pharmacology , Radiation-Sensitizing Agents/chemical synthesisABSTRACT
Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.
Subject(s)
Central Nervous System , Drug Carriers/chemistry , Hyperthermia, Induced , Magnetite Nanoparticles/chemistry , Theranostic Nanomedicine/methods , Animals , Brain Neoplasms/therapy , Cell Survival/drug effects , Central Nervous System/drug effects , Central Nervous System/metabolism , Chemical Phenomena , Drug Delivery Systems , Endothelial Cells/metabolism , Hemolysis , Humans , Hyperthermia, Induced/methods , Magnetic FieldsABSTRACT
BACKGROUND: In this paper we explored thalamocortical functional connectivity in a group of eight patients suffering from peripheral neuropathic pain (diabetic pain), and compared it with that of a group of healthy subjects. We hypothesized that functional interconnections between the thalamus and cortex can be altered after years of ongoing chronic neuropathic pain. RESULTS: Functional connectivity was studied through a resting state functional magnetic resonance imaging (fMRI) paradigm: temporal correlations between predefined regions of interest (primary somatosensory cortex, ventral posterior lateral thalamic nucleus, medial dorsal thalamic nucleus) and the rest of the brain were systematically investigated. The patient group showed decreased resting state functional connectivity between the thalamus and the cortex. CONCLUSION: This supports the idea that chronic pain can alter thalamocortical connections causing a disruption of thalamic feedback, and the view of chronic pain as a thalamocortical dysrhythmia.
Subject(s)
Cerebral Cortex/physiopathology , Diabetic Neuropathies/physiopathology , Pain/physiopathology , Thalamus/physiopathology , Aged , Analysis of Variance , Brain Mapping , Female , Functional Laterality , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Middle Aged , Nerve Net/physiopathology , Neural Pathways/physiopathology , Surveys and QuestionnairesABSTRACT
We examined the functional changes in the activity of the cerebral areas involved in motor tasks, prior to and following a 1-week period of locomotor attention training consisting of physical and mental practice, in normal subjects. In a previous study, we examined the effect of the same kind of training on motor circuits using an fMRI paradigm of motor imagery. In this work, we investigated whether the expanded activations found in the previous study were present also using an overt foot motor task consisting of ankle dorsiflexion; a control task requiring hand movements was also administered. In this article, we also discuss the changes in functional connectivity between the pretraining and posttraining conditions during foot movements. The foot task showed a posttraining reorganization of the sensorimotor areas, which is in line with earlier studies on lower limb motor learning, while the control hand movement task only produced a modification in the left premotor cortex. These results confirm the effect of training on functional reorganization and underline its task specificity. After training, we also observed enhanced connectivity in the sensorimotor areas, suggesting that functional connectivity of the sensorimotor network can be modulated by focusing attention on the movements involved in ambulation.