Biomimetic Nanoparticles as a Theranostic Tool for Traumatic Brain Injury

Zinger, Assaf; Soriano, Sirena; Baudo, Gherardo; Rosa, Enrica De; Taraballi, Francesca; Villapol, Sonia

doi:10.1002/adfm.202100722

Cited by 34 publications

(19 citation statements)

References 60 publications

(75 reference statements)

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“…Most other studies focusing on the biodistribution of NPs after TBI commonly investigated NPs larger than 100 nm. [ 6,7,55 ] It is likely that these particles ended up inside VO, however, the imaging techniques used in these studies did not allow to resolve particle distribution at a cellular level. Thus, by showing for the first time that NPs accumulate inside VO after TBI, our data represent a novel approach to direct pharmacological substances to areas affected by microthrombosis.…”

Section: Discussionmentioning

confidence: 99%

Size‐Selective Transfer of Lipid Nanoparticle‐Based Drug Carriers Across the Blood Brain Barrier Via Vascular Occlusions Following Traumatic Brain Injury

Khalin

Adarsh

Schifferer

et al. 2022

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Moreover, TBI increases the risk of neurodegenerative diseases, such as Alzheimer's or Parkinson's disease. [2] To date, all clinical trials aimed to establish new pharmacological treatment for TBI have failed and thus no efficient therapeutic options exist to protect the brain from additional damage following a traumatic event. [3] A major hurdle for the development of novel pharmacotherapies for the treatment of central nervous system (CNS) disorders, including TBI, is the bloodbrain barrier (BBB). The BBB bars many drugs from entering and accumulating in the brain parenchyma, therefore, BBBpermeable drug formulations often have to be applied in such high concentrations that the risk for adverse reactions is disproportionally elevated. [4,5] Therefore, there is an urgent need for the development of drug delivery systems that transport therapeutic molecules across the BBB and help to treat brain injuries.Many studies have shown the accumulation of nanoscale drug carriers in the CNS after TBI [6,7] or the central effects of their cargoes. [8,9] For instance, we have previously demonstrated The current lack of understanding about how nanocarriers cross the bloodbrain barrier (BBB) in the healthy and injured brain is hindering the clinical translation of nanoscale brain-targeted drug-delivery systems. Here, the bio-distribution of lipid nano-emulsion droplets (LNDs) of two sizes (30 and 80 nm) in the mouse brain after traumatic brain injury (TBI) is investigated. The highly fluorescent LNDs are prepared by loading them with octadecyl rhodamine B and a bulky hydrophobic counter-ion, tetraphenylborate. Using in vivo two-photon and confocal imaging, the circulation kinetics and bio-distribution of LNDs in the healthy and injured mouse brain are studied. It is found that after TBI, LNDs of both sizes accumulate at vascular occlusions, where specifically 30 nm LNDs extravasate into the brain parenchyma and reach neurons. The vascular occlusions are not associated with bleedings, but instead are surrounded by processes of activated microglia, suggesting a specific opening of the BBB. Finally, correlative light-electron microscopy reveals 30 nm LNDs in endothelial vesicles, while 80 nm particles remain in the vessel lumen, indicating size-selective vesicular transport across the BBB via vascular occlusions. The data suggest that microvascular occlusions serve as "gates" for the transport of nanocarriers across the BBB.

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Section: Discussionmentioning

confidence: 99%

Size‐Selective Transfer of Lipid Nanoparticle‐Based Drug Carriers Across the Blood Brain Barrier Via Vascular Occlusions Following Traumatic Brain Injury

Khalin

Adarsh

Schifferer

et al. 2022

Small

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“…[ 34 , 60 , 61 ] One example of potential neurotherapeutic applications of this system is the delivery of neural growth factors to promote outgrowth or synaptic connectivity. The sphere cultures can be used as preclinical screening platform to assess translational potential after injury [ 62 ] or during disease. Further improvements to this approach would strengthen the utility of this nanotechnology for specific applications.…”

Section: Discussionmentioning

confidence: 99%

Humanized Biomimetic Nanovesicles for Neuron Targeting

et al. 2021

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Nanovesicles (NVs) are emerging as innovative, theranostic tools for cargo delivery. Recently, surface engineering of NVs with membrane proteins from specific cell types has been shown to improve the biocompatibility of NVs and enable the integration of functional attributes. However, this type of biomimetic approach has not yet been explored using human neural cells for applications within the nervous system. Here, this paper optimizes and validates the scalable and reproducible production of two types of neuron-targeting NVs, each with a distinct lipid formulation backbone suited to potential therapeutic cargo, by integrating membrane proteins that are unbiasedly sourced from human pluripotent stem-cell-derived neurons. The results establish that both endogenous and genetically engineered cell-derived proteins effectively transfer to NVs without disruption of their physicochemical properties. NVs with neuron-derived membrane proteins exhibit enhanced neuronal association and uptake compared to bare NVs. Viability of 3D neural sphere cultures is not disrupted by treatment, which verifies the utility of organoid-based approaches as NV testing platforms. Finally, these results confirm cellular association and uptake of the biomimetic humanized NVs to neurons within rodent cranial nerves. In summary, the customizable NVs reported here enable next-generation functionalized theranostics aimed to promote neuroregeneration.

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“…However, this method causes minimal damage to the cell membrane itself. Recently, researchers constructed thin-layer evaporation methods and microfluidic-based methods for the preparation of biomimetic nanovesicles ( Zinger et al, 2021a ; Zinger et al, 2021b ). Notably, the biomimetic nanovesicles using microfluidic approach present reproducible and uniform in size, and the microfluidic method can be used for large-scale production without impairing the function of cell membrane proteins ( Molinaro et al, 2018 ).…”

Section: Preparation Of Cell Membrane-coated Nanoparticlesmentioning

confidence: 99%

Engineered Cell Membrane-Derived Nanocarriers: The Enhanced Delivery System for Therapeutic Applications

Xue

Yin

et al. 2022

Front. Cell Dev. Biol.

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There has been a rapid development of biomimetic platforms using cell membranes as nanocarriers to camouflage nanoparticles for enhancing bio-interfacial capabilities. Various sources of cell membranes have been explored for natural functions such as circulation and targeting effect. Biomedical applications of cell membranes-based delivery systems are expanding from cancer to multiple diseases. However, the natural properties of cell membranes are still far from achieving desired functions and effects as a nanocarrier platform for various diseases. To obtain multi-functionality and multitasking in complex biological systems, various functionalized modifications of cell membranes are being developed based on physical, chemical, and biological methods. Notably, many research opportunities have been initiated at the interface of multi-technologies and cell membranes, opening a promising frontier in therapeutic applications. Herein, the current exploration of natural cell membrane functionality, the design principles for engineered cell membrane-based delivery systems, and the disease applications are reviewed, with a special focus on the emerging strategies in engineering approaches.

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Biomimetic Nanoparticles as a Theranostic Tool for Traumatic Brain Injury

Cited by 34 publications

References 60 publications

Size‐Selective Transfer of Lipid Nanoparticle‐Based Drug Carriers Across the Blood Brain Barrier Via Vascular Occlusions Following Traumatic Brain Injury

Size‐Selective Transfer of Lipid Nanoparticle‐Based Drug Carriers Across the Blood Brain Barrier Via Vascular Occlusions Following Traumatic Brain Injury

Humanized Biomimetic Nanovesicles for Neuron Targeting

Engineered Cell Membrane-Derived Nanocarriers: The Enhanced Delivery System for Therapeutic Applications

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