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Surface-engineered multimodal magnetic nanoparticles to manage CNS diseases.

ABSTRACT: Advanced central nervous system (CNS) therapies exhibited high efficacy but complete treatment of CNS diseases remains challenging owing to limited delivery of therapeutic agents to the brain. Multifunctional magnetic nanoparticles are investigated not only for site-specific drug delivery but also for theranostic applications aiming for an effective CNS therapy. Recently, surface engineering of magnetic nanoparticles was recognized as a crucial area of research to achieve precise therapy and imaging at molecular and cellular levels. This review reports state-of-the-art advancement in the development of surface-engineered magnetic nanoparticles targeting CNS diagnostics and therapies. The challenges and future prospects of magnetic theranostics are also discussed by considering the translation from bench to bedside. Successful translation of magnetic theranostics to the clinical setting will enable precise and efficient diagnostics and therapy to manage CNS diseases.

SUBMITTER: Tomitaka A

PROVIDER: S-EPMC7405805 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Surface-engineered multimodal magnetic nanoparticles to manage CNS diseases.

Tomitaka Asahi A Kaushik Ajeet A Kevadiya Bhavesh D BD Mukadam Insiya I Gendelman Howard E HE Khalili Kamel K Liu Gang G Nair Madhavan M

Drug discovery today 20190117 3

Advanced central nervous system (CNS) therapies exhibited high efficacy but complete treatment of CNS diseases remains challenging owing to limited delivery of therapeutic agents to the brain. Multifunctional magnetic nanoparticles are investigated not only for site-specific drug delivery but also for theranostic applications aiming for an effective CNS therapy. Recently, surface engineering of magnetic nanoparticles was recognized as a crucial area of research to achieve precise therapy and ima ...[more]

PMID: 30660756

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Project description:Eighty percent of lung cancers originate as subtle premalignant changes in the airway mucosal epithelial layer of bronchi and alveoli, which evolve and penetrate deeper into the parenchyma. Liquid-ventilation, with perfluorocarbons (PFC) was first demonstrated in rodents in 1966 then subsequently applied as lipid-encapsulated PFC emulsions to improve pulmonary function in neonatal infants suffering with respiratory distress syndrome in 1996. Subsequently, PFC nanoparticles (NP) were extensively studied as intravenous (IV) vascular-constrained nanotechnologies for diagnostic imaging and targeted drug delivery applications. Methods: This proof-of-concept study compared intratumoral localization of fluorescent paramagnetic (M) PFC NP in the Vx2 rabbit model using proton (1H) and fluorine (19F) magnetic resonance (MR) imaging (3T) following intratracheal (IT) or IV administration. MRI results were corroborated by fluorescence microscopy. Results: Dynamic 1H-MR and 19F-MR images (3T) obtained over 72 h demonstrated marked and progressive accumulation of M-PFC NP within primary lung Vx2 tumors during the first 12 h post IT administration. Marked 1H and 19F MR signal persisted for over 72 h. In contradistinction, IV M-PFC NP produced a modest transient signal during the initial 2 h post-injection that was consistent circumferential blood pool tumor enhancement. Fluorescence microscopy of excised tumors corroborated the MR results and revealed enormous intratumor NP deposition on day 3 after IT but not IV treatment. Rhodamine-phospholipid incorporated into the PFC nanoparticle surfactant was distributed widely within the tumor on day 3, which is consistent with a hemifusion-based contact drug delivery mechanism previously reported. Fluorescence microscopy also revealed similar high concentrations of M-PFC NP given IT for metastatic Vx2 lung tumors. Biodistribution studies in mice revealed that M-PFC NP given IV distributed into the reticuloendothelial organs, whereas, the same dosage given IT was basically not detected beyond the lung itself. PFC NP given IT did not impact rabbit behavior or impair respiratory function. PFC NP effects on cells in culture were negligible and when given IV or IT no changes in rabbit hematology nor serum clinical chemistry parameters were measured. Conclusion: IT delivery of PFC NP offered unique opportunity to locally deliver PFC NP in high concentrations into lung cancers with minimal extratumor systemic exposure.

Project description:Despite the lifesaving medical discoveries of the last century, there is still an urgent need to improve the curative rate and reduce mortality in many fatal diseases such as cancer. One of the main requirements is to find new ways to deliver therapeutics/drugs more efficiently and only to affected tissues/organs. An exciting new technology is nanomaterials which are being widely investigated as potential nanocarriers to achieve localized drug delivery that would improve therapy and reduce adverse drug side effects. Among all the nanocarriers, iron oxide nanoparticles (IONPs) are one of the most promising as, thanks to their paramagnetic/superparamagnetic properties, they can be easily modified with chemical and biological functions and can be visualized inside the body by magnetic resonance imaging (MRI), while delivering the targeted therapy. Therefore, iron oxide nanoparticles were produced here with a novel method and their properties for potential applications in both diagnostics and therapeutics were investigated. The novel method involves production of free standing IONPs by inert gas condensation via the Mantis NanoGen Trio physical vapor deposition system. The IONPs were first sputtered and deposited on plasma cleaned, polyethylene glycol (PEG) coated silicon wafers. Surface modification of the cleaned wafer with PEG enabled deposition of free-standing IONPs, as once produced, the soft-landed IONPs were suspended by dissolution of the PEG layer in water. Transmission electron microscopic (TEM) characterization revealed free standing, iron oxide nanoparticles with size < 20 nm within a polymer matrix. The nanoparticles were analyzed also by Atomic Force Microscope (AFM), Dynamic Light Scattering (DLS) and NanoSight Nanoparticle Tacking Analysis (NTA). Therefore, our work confirms that inert gas condensation by the Mantis NanoGen Trio physical vapor deposition sputtering at room temperature can be successfully used as a scalable, reproducible process to prepare free-standing IONPs. The PEG- IONPs produced in this work do not require further purification and thanks to their tunable narrow size distribution have potential to be a powerful tool for biomedical applications.

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Surface-engineered multimodal magnetic nanoparticles to manage CNS diseases.

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Surface-engineered multimodal magnetic nanoparticles to manage CNS diseases.

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