Abstract:Ex vivo-loaded white blood cells (WBC)
can transfer
cargo to pathological foci in the central nervous system (CNS). Here
we tested affinity ligand driven in vivo loading
of WBC in order to bypass the need for ex vivo WBC
manipulation. We used a mouse model of acute brain inflammation caused
by local injection of tumor necrosis factor alpha (TNF-α). We
intravenously injected nanoparticles targeted to intercellular adhesion
molecule 1 (anti-ICAM/NP). We found that (A) at 2 h, >20% of anti-ICAM/NP
were localized … Show more
“…This system shows promise for improved pharmacotherapy of epilepsy and potentially other CNS disorders . In another study, Nong et al demonstrated that targeting the adhesion molecule ICAM-1 enabled the transport of NPs across the BBB. They intravenously injected NPs conjugated to anti-ICAM-1 antibodies.…”
Section: Properties
Affecting Nanoparticle Crossing Through
the Bbbmentioning
confidence: 99%
“…Histology showed nanoparticles largely colocalized with macrophages in the brain parenchyma. In summary, targeting ICAM-1 enables leukocytes to act as Trojan horses to carry the NPs across the BBB during neuroinflammation …”
Section: Properties
Affecting Nanoparticle Crossing Through
the Bbbmentioning
The blood−brain barrier (BBB) is a specialized semipermeable structure that highly regulates exchanges between the central nervous system parenchyma and blood vessels. Thus, the BBB also prevents the passage of various forms of therapeutic agents, nanocarriers, and their cargos. Recently, many multidisciplinary studies focus on developing cargo-loaded nanoparticles (NPs) to overcome these challenges, which are emerging as safe and effective vehicles in neurotheranostics. In this Review, first we introduce the anatomical structure and physiological functions of the BBB. Second, we present the endogenous and exogenous transport mechanisms by which NPs cross the BBB. We report various forms of nanomaterials, carriers, and their cargos, with their detailed BBB uptake and permeability characteristics. Third, we describe the effect of regulating the size, shape, charge, and surface ligands of NPs that affect their BBB permeability, which can be exploited to enhance and promote neurotheranostics. We classify typical functionalized nanomaterials developed for BBB crossing. Fourth, we provide a comprehensive review of the recent progress in developing functional polymeric nanomaterials for applications in multimodal bioimaging, therapeutics, and drug delivery. Finally, we conclude by discussing existing challenges, directions, and future perspectives in employing functionalized nanomaterials for BBB crossing.
“…This system shows promise for improved pharmacotherapy of epilepsy and potentially other CNS disorders . In another study, Nong et al demonstrated that targeting the adhesion molecule ICAM-1 enabled the transport of NPs across the BBB. They intravenously injected NPs conjugated to anti-ICAM-1 antibodies.…”
Section: Properties
Affecting Nanoparticle Crossing Through
the Bbbmentioning
confidence: 99%
“…Histology showed nanoparticles largely colocalized with macrophages in the brain parenchyma. In summary, targeting ICAM-1 enables leukocytes to act as Trojan horses to carry the NPs across the BBB during neuroinflammation …”
Section: Properties
Affecting Nanoparticle Crossing Through
the Bbbmentioning
The blood−brain barrier (BBB) is a specialized semipermeable structure that highly regulates exchanges between the central nervous system parenchyma and blood vessels. Thus, the BBB also prevents the passage of various forms of therapeutic agents, nanocarriers, and their cargos. Recently, many multidisciplinary studies focus on developing cargo-loaded nanoparticles (NPs) to overcome these challenges, which are emerging as safe and effective vehicles in neurotheranostics. In this Review, first we introduce the anatomical structure and physiological functions of the BBB. Second, we present the endogenous and exogenous transport mechanisms by which NPs cross the BBB. We report various forms of nanomaterials, carriers, and their cargos, with their detailed BBB uptake and permeability characteristics. Third, we describe the effect of regulating the size, shape, charge, and surface ligands of NPs that affect their BBB permeability, which can be exploited to enhance and promote neurotheranostics. We classify typical functionalized nanomaterials developed for BBB crossing. Fourth, we provide a comprehensive review of the recent progress in developing functional polymeric nanomaterials for applications in multimodal bioimaging, therapeutics, and drug delivery. Finally, we conclude by discussing existing challenges, directions, and future perspectives in employing functionalized nanomaterials for BBB crossing.
“…There are continuing efforts for engineering targeted nucleic acid therapeutics. Pseudotyping viral vectors and virus-like particles with different surface glycoproteins have been shown to alter their tropism in vitro and in vivo . ,, Adding targeting moieties such as peptides or antibodies to lipid nanoparticles has been shown to be effective in improving their specificity of uptake to target cells. , Ongoing development of new lipids and polymers via combinatorial chemistry , for nonviral vectors and the development of directed evolution and computational design approaches for viral vectors are also expected to improve targeted delivery capabilities of these therapeutic vectors. Subcellular level targeting strategies also need to be considered since nuclear entry and integration of the nucleic acid cargo at specific genomic sites may be required for some treatment modalities …”
Section: Challenges and Future Directionsmentioning
In medicine, it is desirable for clinicians to be able to restore function and imbue novel function into selected cells for therapy and disease prevention. Cells damaged by disease, injury, or aging could be programmed to restore normal or lost functions, such as retinal cells in inherited blindness and neuronal cells in Alzheimer's disease. Cells could also be genetically programmed with novel functions such as immune cells expressing synthetic chimeric antigen receptors for immunotherapy. Furthermore, knockdown or modification of risk factor proteins can mitigate disease development. Currently, nucleic acids are emerging as a versatile and potent therapeutic modality for achieving this cellular programming. In this review, we highlight the latest developments in nanobiomaterials-based nucleic acid therapeutics for cellular programming from a biomaterial design and delivery perspective and how to overcome barriers to their clinical translation to benefit patients.
“…The engineered nanostructures enabled the successful deployment of the COVID-19 vaccine. To safely deliver the fragile mRNA to human cells, designing novel lipid-based structures and compositions enabled RNA protection and enhanced its uptake into cells. ,,, The success of the mRNA technology during the COVID-19 pandemic inspired academics, industries, and governments to expand its therapeutic applicationsto address other infectious pathogens, personalized cancer vaccines, rare diseases, and other medically debilitating diseases.…”
mentioning
confidence: 99%
“…However, in 2005, Katalin Karikó and Drew Weissman solved this problem by modifying mRNA bases, which led to increased protein translation. They published a body of work establishing the feasibility of mRNA-based therapies. − …”
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