ABSTRACT
A novel magnetically guidable nanobubble is designed for disrupting the blood-brain barrier (BBB) by combining magnetic guidance with focused ultrasound in vivo. The magnetic-nanobubble platform also demonstrates the potential to serve as a unique theranostic tool via performing focused ultrasound (FUS)-induced BBB disruption and magnetic resonance imaging (MRI)/ultrasound dual-modality contrast-agent imaging to improve the drug delivery of therapeutic substances or gene therapy into the central nervous system.
Subject(s)
Blood-Brain Barrier/metabolism , Magnetic Phenomena , Nanoparticles/therapeutic use , Ultrasonics , Animals , Contrast Media/chemistry , Ferric Compounds/chemistry , Mice , Nanoparticles/chemistry , Silicon Dioxide/chemistryABSTRACT
Nanobubbles can serve as promising, next-generation theranostic platforms for ultrasound (US) and magnetic resonance (MR) imaging, and combined magnetic targeting (MT) and high-intensity focused ultrasound (HIFU)-triggered drug release for tumor therapy. Nanobubble-based dual contrast enhancement agents encapsulated with perfluoropentane and stabilized with superparamagnetic iron oxide (SPIO) nanoparticles have been synthesized through a single-step emulsion process from thermosensitive F127 and polyacrylic acid (PAA). Both US and MR imaging contrast can be optimized by varying the shell thickness and SPIO-embedded concentration. The US contrast can be enhanced from a mean gray value of 62 to 115, and the MR r2 value can be enhanced from 164 to 208 (s(-1)mM (-1)Fe) by increasing the SPIO concentration from 14.1 to 28.2mg/mL, respectively. In vivo investigations of SPIO-embedded nanobubbles in excised tumors under external MT revealed that the US and MR signals change quantitatively compared to the same site without MT. This combined strategy enables the nanobubbles to enhance both passive targeting (increasing the permeability by HIFU) and physical MT of chemotherapeutic drugs to tumors. The integration of functionalities makes this nanobubble system a powerful and viable new tool to achieve simultaneous in vivo tumor imaging and efficacious cancer therapy.
Subject(s)
Acrylic Resins , Drug Delivery Systems/methods , Magnetic Resonance Imaging/methods , Magnetite Nanoparticles , Neoplasms/diagnosis , Neoplasms/drug therapy , Polyethylenes , Polypropylenes , Acrylic Resins/chemistry , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Contrast Media/chemistry , Female , Magnetite Nanoparticles/chemistry , Magnetite Nanoparticles/ultrastructure , Mice , Mice, Nude , Microbubbles , Models, Molecular , Polyethylenes/chemistry , Polypropylenes/chemistry , Rats , Rats, Wistar , Ultrasonics/methodsABSTRACT
A novel method for control burst releasing of drug via a high frequency magnetic field (HFMF) from magnetic-sensitive silica nanospheres was developed. The nanospheres were synthesized by a combination of emulsion and sol-gel process with the particles controlled at about 80 nm in diameter. Under repeated exposures to the high frequency magnetic stimulus, the drug release behaviors showed reproducible slow-to-burst profiles while consecutively applying the magnetic stimulus at 10-min switching time and the release profile restored immediately when the stimulus was removed. By taking this non-contact control-burst method, the magnetic silica nanospheres can be designed to treat the cancer therapy and urgent physiological needs.
Subject(s)
Magnetics , Nanospheres , Pharmaceutical Preparations/chemistry , Silicon Dioxide , Microscopy, Electron, Scanning , Microscopy, Electron, TransmissionABSTRACT
Recently, magnetic silica-based nanospheres have received great attention and displayed magnificent potential for bioimaging and therapeutic purposes. This study provided a way to accelerate drug release from magnetic-sensitive silica nanospheres by controlled bursting to a therapeutically effective concentration by a high-frequency magnetic field (HFMF). The magnetic-sensitive silica nanospheres were synthesized by an in situ process, with particle sizes about 50 nm and able to release specific amounts of drug in a burst manner via short exposure to a HFMF. The HFMF accelerates the rotation of magnetic nanoparticles deposited in the silica matrix with generated heat energy and subsequently enlarges the nanostructure of the silica matrix to produce porous channels that cause the drug to be released easily. By taking these magnetic-responsive controllable drug release behaviors, the magnetic silica nanospheres can be designed for controlled burst release of therapeutic agents for especially urgent physiological needs.
