Cell Delivery of Therapeutic Nanoparticles

McMillan, JoEllyn M; Batrakova, Elena V.; Gendelman, Howard E.

doi:10.1016/b978-0-12-416020-0.00014-0

Cited by 122 publications

(71 citation statements)

References 254 publications

(276 reference statements)

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“…Moreover, naked nanoparticles are rapidly engulfed by macrophages and cleared from the body before reaching targets. 24,41 A dense coating of PEG on particles of small size (#10 nm) has been reported for effective brain targeting and diffusion within the brain tissue. 29,30 In the present study, we synthesized 3 nm spherical CNPs with PEG coating for effective brain localization.…”

Section: Discussionmentioning

confidence: 99%

Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK–PKC–CBP signaling cascade

Arya¹,

Gangwar²,

Singh³

et al. 2016

IJN

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Structural and functional integrity of the brain is adversely affected by reduced oxygen saturation, especially during chronic hypoxia exposure and often encountered by altitude travelers or dwellers. Hypoxia-induced generation of reactive nitrogen and oxygen species reportedly affects the cortex and hippocampus regions of the brain, promoting memory impairment and cognitive dysfunction. Cerium oxide nanoparticles (CNPs), also known as nanoceria, switch between +3 and +4 oxidation states and reportedly scavenge superoxide anions, hydrogen peroxide, and peroxynitrite in vivo. In the present study, we evaluated the neuroprotective as well as the cognition-enhancing activities of nanoceria during hypobaric hypoxia. Using polyethylene glycol-coated 3 nm nanoceria (PEG-CNPs), we have demonstrated efficient localization of PEG-CNPs in rodent brain. This resulted in significant reduction of oxidative stress and associated damage during hypoxia exposure. Morris water maze-based memory function tests revealed that PEG-CNPs ameliorated hypoxia-induced memory impairment. Using microscopic, flow cytometric, and histological studies, we also provide evidences that PEG-CNPs augmented hippocampus neuronal survival and promoted neurogenesis. Molecular studies revealed that PEG-CNPs promoted neurogenesis through the 5′-adenine monophosphate-activated protein kinase–protein kinase C–cyclic adenosine monophosphate response element-binding protein binding (AMPK-PKC-CBP) protein pathway. Our present study results suggest that nanoceria can be translated as promising therapeutic molecules for neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK–PKC–CBP signaling cascade

Arya¹,

Gangwar²,

Singh³

et al. 2016

IJN

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“…This may occur by repackaging traditional antiretroviral medications into nanoART vectors to facilitate cell-based delivery of drug and, as such, improve ART pharmacokinetics and biodistribution. 13 To this end, our prior works demonstrated limited cytotoxicity of nanoART to monocytes and macrophages 14 and efficient macrophage uptake, distribution, and release of nanoART in both in vitro and animal models of human disease. [15][16][17] Macrophage drug carriers were able to deliver ART to the same tissue sites where active HIV-1 replication ensues.…”

Section: Introductionmentioning

confidence: 99%

Mononuclear phagocyte intercellular crosstalk facilitates transmission of cell-targeted nanoformulated antiretroviral drugs to human brain endothelial cells

Kanmogne¹,

Singh²,

Roy³

et al. 2012

IJN

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Despite the successes of antiretroviral therapy (ART), HIV-associated neurocognitive disorders remain prevalent in infected people. This is due, in part, to incomplete ART penetration across the blood-brain barrier (BBB) and lymph nodes and to the establishment of viral sanctuaries within the central nervous system. In efforts to improve ART delivery, our laboratories developed a macrophage-carriage system for nanoformulated crystalline ART (nanoART) (atazanavir, ritonavir, indinavir, and efavirenz). We demonstrate that nanoART transfer from mononuclear phagocytes (MP) to human brain microvascular endothelial cells (HBMEC) can be realized through cell-to-cell contacts, which can facilitate drug passage across the BBB. Coculturing of donor MP containing nanoART with recipient HBMEC facilitates intercellular particle transfer. NanoART uptake was observed in up to 52% of HBMEC with limited cytotoxicity. Folate coating of nanoART increased MP to HBMEC particle transfer by up to 77%. To translate the cell assays into relevant animal models of disease, ritonavir and atazanavir nanoformulations were injected into HIV-1-infected NOD/scid-γ c null mice reconstituted with human peripheral blood lymphocytes. Atazanavir and ritonavir levels in brains of mice treated with folate-coated nanoART were three-to four-fold higher than in mice treated with noncoated particles. This was associated with decreased viral load in the spleen and brain, and diminished brain CD11b-associated glial activation. We postulate that monocyte-macrophage transfer of nanoART to brain endothelial cells could facilitate drug entry into the brain.

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“…In addition, tumor-tropic stem cells have also been shown to deliver nanoparticles loaded with chemotherapy and oncolytic viruses. The accumulation of effective concentrations of nanoparticles within GBM tissue could be increased using a stem cell-based strategy to bypass the BBB (37,38). The efficiency and safety of delivering GBM-targeted oncolytic viruses have also been enhanced using tumor-tropic stem cells (39,40).…”

Section: Controllable Drug Delivery Using Stem Cells In Conjunction Wmentioning

confidence: 99%

Maximizing Local Access to Therapeutic Deliveries in Glioblastoma. Part IV: Image- Guided, Remote-Controlled Opening of the Blood–Brain Barrier for Systemic Brain Tumor Therapy

et al. 2017

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Disease in the central nervous system (CNS) is a challenge to treat with systemic therapies due to the presence of the blood-brain barrier (BBB), which excludes common and novel therapeutics. For example, glioblastoma (GBM) is the most common and aggressive primary brain tumor, with an extremely poor prognosis due to infiltrating tumor cells in areas of normal brain. A primary On-Demand Opening of the BBB 396 challenge of treating this devastating disease is the exclusion of systemic therapies from the CNS. While efforts are being made to develop strategies for designing drugs that can pass through the BBB, there are also efforts to use novel engineering techniques to safely allow any systemic therapy into the CNS and areas of disease. In this chapter, we focus on using high-intensity focused ultrasound (HIFU) to circumvent the BBB.

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Cell Delivery of Therapeutic Nanoparticles

Cited by 122 publications

References 254 publications

Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK–PKC–CBP signaling cascade

Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK–PKC–CBP signaling cascade

Mononuclear phagocyte intercellular crosstalk facilitates transmission of cell-targeted nanoformulated antiretroviral drugs to human brain endothelial cells

Maximizing Local Access to Therapeutic Deliveries in Glioblastoma. Part IV: Image- Guided, Remote-Controlled Opening of the Blood–Brain Barrier for Systemic Brain Tumor Therapy

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Cell Delivery of Therapeutic Nanoparticles

Cited by 122 publications

References 254 publications

Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK&ndash;PKC&ndash;CBP signaling cascade

Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK&ndash;PKC&ndash;CBP signaling cascade

Mononuclear phagocyte intercellular crosstalk facilitates transmission of cell-targeted nanoformulated antiretroviral drugs to human brain endothelial cells

Maximizing Local Access to Therapeutic Deliveries in Glioblastoma. Part IV: Image- Guided, Remote-Controlled Opening of the Blood–Brain Barrier for Systemic Brain Tumor Therapy

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Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK–PKC–CBP signaling cascade

Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK–PKC–CBP signaling cascade