In Vivo Wireless Brain Stimulation via Non-invasive and Targeted Delivery of Magnetoelectric Nanoparticles

AbstractNon-invasive brain stimulation is valuable for studying neural circuits and treating various neurological disorders in humans. However, the current technologies usually have low spatial and temporal precision and poor brain penetration, which greatly limit their application. A new class of nanoparticles known as magneto-electric nanoparticles (MENs) can be navigated to a targeted brain region with a magnetic field and is highly efficient in converting an externally applied magnetic wave into local electric fields for neuronal activity modulation. Here we developed a new method to fabricate MENs of CoFe2O4-BaTiO3 core-shell structure that had excellent magneto-electrical coupling properties. Using calcium imaging of organotypic and acute cortical slices from GCaMP6s transgenic mice, we demonstrated their efficacy in reliably evoking neuronal responses with a short latency period. For in vivo non-invasive delivery of MENs to brain, fluorescently labeled MENs were intravenously injected and guided to pass through the blood brain barrier to a targeted brain region by applying a magnetic field gradient. A magnetic field (∼450 Oe at 10 Hz) applied to mouse brain was able to reliably evoke cortical activities, as revealed by in vivo two-photon and mesoscopic imaging of calcium signals at both cellular and global network levels. The effect was further confirmed by the increased number of c-Fos expressing cells after stimulation. Neither brain delivery of MENs nor the subsequent magnetic stimulation caused any significant increases in the numbers of GFAP and IBA1 positive astrocytes and microglia in the brain. This study demonstrates the feasibility of using MENs as a novel efficient and non-invasive technique of contactless deep brain stimulation that may have great potential for translation.

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Multiplexed Non-invasive in vivo Imaging to Assess Metabolism and Receptor Engagement in Tumor Xenografts

10.1101/758383 ◽

2019 ◽

Author(s):

Alena Rudkouskaya ◽

Nattawut Sinsuebphon ◽

Marien Ochoa ◽

Joe E. Mazurkiewicz ◽

Xavier Intes ◽

...

Keyword(s):

Drug Delivery ◽

Targeted Delivery ◽

Near Infrared ◽

Metabolic Response ◽

Imaging Modalities ◽

Wide Field ◽

Receptor Ligand ◽

Non Invasive ◽

Intracellular Drug Delivery

AbstractFollowing an ever-increased focus on personalized medicine, there is a continuing need to develop preclinical molecular imaging modalities to guide the development and optimization of targeted therapies. To date, non-invasive quantitative imaging modalities that can comprehensively assess simultaneous cellular drug delivery efficacy and therapeutic response are lacking. In this regard, Near-Infrared (NIR) Macroscopic Fluorescence Lifetime Förster Resonance Energy Transfer (MFLI-FRET) imaging offers a unique method to robustly quantify receptor-ligand engagement in vivo and subsequent intracellular internalization, which is critical to assess the delivery efficacy of targeted therapeutics. However, implementation of multiplexing optical imaging with FRET in vivo is challenging to achieve due to spectral crowding and cross-contamination. Herein, we report on a strategy that relies on a dark quencher that enables simultaneous assessment of receptor-ligand engagement and tumor metabolism in intact live mice. First, we establish that IRDye QC-1 (QC-1) is an effective NIR dark acceptor for the FRET-induced quenching of donor Alexa Fluor 700 (AF700) using in vitro NIR FLI microscopy and in vivo wide-field MFLI imaging. Second, we report on simultaneous in vivo imaging of the metabolic probe IRDye 800CW 2-deoxyglucose (2-DG) and MFLI-FRET imaging of NIR-labeled transferrin FRET pair (Tf-AF700/Tf-QC-1) uptake in tumors. Such multiplexed imaging revealed an inverse relationship between 2-DG uptake and Tf intracellular delivery, suggesting that 2-DG signal may predict the efficacy of intracellular targeted delivery. Overall, our methodology enables for the first time simultaneous non-invasive monitoring of intracellular drug delivery and metabolic response in preclinical studies.

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Nanobiotechnology medical applications: Overcoming challenges through innovation

The EuroBiotech Journal ◽

10.2478/ebtj-2018-0019 ◽

2018 ◽

Vol 2 (3) ◽

pp. 146-160 ◽

Cited By ~ 2

Author(s):

Anthony Singer ◽

Eleni Markoutsa ◽

Alya Limayem ◽

Subhra Mohapatra ◽

Shyam S. Mohapatra

Keyword(s):

Targeted Delivery ◽

Surgical Techniques ◽

Interdisciplinary Approach ◽

Pharmacokinetic Profile ◽

Diagnostic Techniques ◽

Stimuli Responsive ◽

Diagnostic Assays ◽

Non Invasive

AbstractBiomedical Nanotechnology (BNT) has rapidly become a revolutionary force that is driving innovation in the medical field. BNT is a subclass of nanotechnology (NT), and often operates in cohort with other subclasses, such as mechanical or electrical NT for the development of diagnostic assays, therapeutic implants, nano-scale imaging systems, and medical machinery. BNT is generating solutions to many conventional challenges through the development of enhanced therapeutic delivery systems, diagnostic techniques, and theranostic therapies. Therapeutically, BNT has generated many novel nanocarriers (NCs) that each express specifically designed physiochemical properties that optimize their desired pharmacokinetic profile. NCs are also being integrated into nanoscale platforms that further enhance their delivery by controlling and prolonging their release profile. Nano-platforms are also proving to be highly efficient in tissue regeneration when combined with the appropriate growth factors. Regarding diagnostics, NCs are being designed to perform targeted delivery of luminescent tags and contrast agents that enhance the NC -aided imaging capabilities and resulting diagnostic accuracy of the presence of diseased cells. This technology has also been advancing the ability for surgeons to practice true precision surgical techniques. Incorporating therapeutic and diagnostic NC-components within a single NC can facilitate both functions, referred to as theranostics, which facilitates real-time in vivo tracking and observation of drug release events via enhanced imaging. Additionally, stimuli-responsive theranostic NCs are quickly developing as vectors for tumor ablation therapies by providing a model that facilitates the location of cancer cells for the application of an external stimulus. Overall, BNT is an interdisciplinary approach towards health care, and has the potential to significantly improve the quality of life for humanity by significantly decreasing the treatment burden for patients, and by providing non-invasive therapeutics that confer enhanced therapeutic efficiency and safety

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Biomimetic Metal-organic Framework Nanoparticles for Synergistic Combining of SDT-chemotherapy Induce Pyroptosis in Gastric Cancer

10.21203/rs.3.rs-594583/v1 ◽

2021 ◽

Author(s):

zhu yu ◽

Wenlong Cao ◽

Chuangye Han ◽

Zhen Wang ◽

Yue Qiu ◽

...

Keyword(s):

Gastric Cancer ◽

Targeted Delivery ◽

Metal Organic Framework ◽

Ultrasound Irradiation ◽

Non Invasive ◽

In Vivo Experiments ◽

Metal Organic ◽

Zeolitic Imidazole Frameworks

Abstract In recent years, sonodynamic therapy (SDT) has been widely developed for cancer research as a promising non-invasive therapeutic strategy. Here, we synthesized Zeolitic imidazole frameworks-8 (ZIF-8) and utilized its properties to encapsulate hydrophobic Chlorin e6 (Ce6) and hydrophilic tirapazamine (TPZ) for a synergistic sonodynamic-chemotherapy, which was also accompanied by the modification of cytomembrane of gastric cancer (GC) cells. Thus, we enabled the biomimetic property to achieve targeted delivery. Ce6-mediated SDT, in combination with ultrasound irradiation, could target the release of reactive oxygen species (ROS) to aggravate further hypoxia, which activated TPZ. Combining these effects could induce the pyroptosis of GC cells. Both in vitro and in vivo experiments showed that the nanoparticle had good biocompatibility and anti-cancer function, which could provide a potential therapeutic method for cancer therapy.

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