Spontaneous penetration of gold nanoparticles through the blood brain barrier (BBB)

Sela, Hagit; Cohen, Hagit; Elia, Paz; Zach, Raya; Karpas, Zeev; Zeiri, Yehuda

doi:10.1186/s12951-015-0133-1

Cited by 97 publications

(69 citation statements)

References 43 publications

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“…They are available in a wide variety of optical and electric features and structures, such as nanospheres and nanorods [110]. AuNPs have low toxicity and also easily cross the BBB [111]. For example, a wheat germ agglutinin horseradish peroxidase (WGA-HRP) conjugated AuNPs has been shown to be able to cross the BBB through intramuscular injection in the diaphragm of rats [112].…”

Section: Nanocarriers Nanoparticles and Vectorsmentioning

confidence: 99%

Overcoming the Blood–Brain Barrier. Challenges and Tricks for CNS Drug Delivery

2019

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Treatment of certain central nervous system disorders, including different types of cerebral malignancies, is limited by traditional oral or systemic administrations of therapeutic drugs due to possible serious side effects and/or lack of the brain penetration and, therefore, the efficacy of the drugs is diminished. During the last decade, several new technologies were developed to overcome barrier properties of cerebral capillaries. This review gives a short overview of the structural elements and anatomical features of the blood–brain barrier. The various in vitro (static and dynamic), in vivo (microdialysis), and in situ (brain perfusion) blood–brain barrier models are also presented. The drug formulations and administration options to deliver molecules effectively to the central nervous system (CNS) are presented. Nanocarriers, nanoparticles (lipid, polymeric, magnetic, gold, and carbon based nanoparticles, dendrimers, etc.), viral and peptid vectors and shuttles, sonoporation and microbubbles are briefly shown. The modulation of receptors and efflux transporters in the cell membrane can also be an effective approach to enhance brain exposure to therapeutic compounds. Intranasal administration is a noninvasive delivery route to bypass the blood–brain barrier, while direct brain administration is an invasive mode to target the brain region with therapeutic drug concentrations locally. Nowadays, both technological and mechanistic tools are available to assist in overcoming the blood–brain barrier. With these techniques more effective and even safer drugs can be developed for the treatment of devastating brain disorders.

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Section: Nanocarriers Nanoparticles and Vectorsmentioning

confidence: 99%

Overcoming the Blood–Brain Barrier. Challenges and Tricks for CNS Drug Delivery

2019

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“…17 Moreover, AuNPs can pass through the BBB, thereby functioning as ideal vectors for the treatment of brain tumors. 18,19 However, when RNA-loaded AuNPs are administered intravenously, nucleases in the blood may degrade the nucleic acid cargoes, and the efficiency of passage through the BBB remains suboptimal. 19,20 Notably, the olfactory pathway is a route that connects the brain to the outside environment.…”

Section: Introductionmentioning

confidence: 99%

<p>Intranasal Delivery of Immunotherapeutic Nanoformulations for Treatment of Glioma Through in situ Activation of Immune Response</p>

Yin¹,

Li²,

Ke³

et al. 2020

IJN

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Purpose: Some chemotherapeutics have been shown to induce both the release of damageassociated molecular patterns (DAMPs) and the production of type I interferon (IFN-I), leading to immunogenic cell death (ICD). However, the standard chemotherapy drug for glioma, temozolomide (TMZ), cannot induce ICD as it cannot activate IFN-I signaling. Moreover, inefficient delivery of immunostimulants across the blood-brain barrier (BBB) is the main obstacle to overcome in order to induce local immune responses in the brain. Methods: A new oligonucleotide nanoformulation (Au@PP)/poly(I:C)) was constructed by coating gold nanoparticles (AuNPs) with methoxypolyethylene glycol (mPEG)-detachable (d)-polyethyleneimine (PEI) (Au@PP) followed by inducing the formation of electrostatic interactions with polyinosinic-polycytidylic acid (poly(I:C)). Intracranial GL261 tumorbearing C57BL/6 mice were used to explore the therapeutic outcomes of Au@PP/poly(I:C) plus TMZ in vivo. The anti-tumor immune response in the brain induced by this treatment was analyzed by RNA sequencing and immunohistochemical analyses. Results: Au@PP/poly(I:C) induced IFN-I production after endocytosis into glioma cells in vitro. Additionally, Au@PP/poly(I:C) was efficiently accumulated in the glioma tissue after intranasal administration, which allowed the nanoformulation to enter the brain while bypassing the BBB. Furthermore, Au@PP/poly(I:C) plus TMZ significantly improved the overall survival of the tumor-bearing mice compared with group TMZ only. RNA sequencing and immunohistochemical analyses revealed efficient immune response activation and T lymphocyte infiltration in the Au@PP/poly(I:C) plus TMZ group. Conclusion: This study demonstrates that intranasal administration of Au@PP/poly(I:C) combined with TMZ induces ICD, thereby stimulating an in situ immune response to inhibit glioma growth.

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“…It is not completely known if AuNPs persist in the lifetime of the animals. Work demonstrated by Sela et al estimated that the half‐life of 1.3 nm sized AuNPs was a mere 12.9 ± 4.9 h . However, after acute inhalation of noncoated AuNPs (18.7 nm agglomerates) by mice, AuNPs could be detected as early as 15 min and was found in blood after three months indicating that AuNP size may influence the half‐life and retention .…”

Section: Size and Surface Coating Affects Retention Excretion And Hmentioning

confidence: 99%

Design of Gold Nanoparticles in Dendritic Cell‐Based Vaccines

Dings

Cannon

Vang

2018

Part & Part Syst Charact

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The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/ppsc.201800109.The design of effective cancer vaccines must be able to activate dendritic cells (DCs) of the innate immune system in order to induce immunity to pathogens and cancer. DCs patrol the body and once they encounter antigens, they orchestrate a complex mechanism of events and signals that can alert the adaptive immune system to action. However, DC-based vaccines remain a challenge in part because the source and quality of antigens, the DC targeting molecule, type of adjuvant, and delivery vehicle must be optimized to induce a robust immune response. Gold nanoparticles (AuNPs) have now entered clinical trials as carriers due to their ease of functionalization with antigens, adjuvants, and targeting molecules. This progress report discusses how AuNPs can influence DC activation and maturation, as well as their potential impact on T helper (Th) differentiation. Ultimately, successful AuNP-based DC vaccines are able to induce phagocytosis, activation/maturation, migration, T cell costimulation, and cytokine secretion, which is named AuNP-induced DC tuning (AuNP-DC tuning). Although at its infancy, understanding the processes of AuNP-DC tuning will give a better understanding of how best to engineer AuNPs and will redefine the next generation of DC-based vaccines.

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Spontaneous penetration of gold nanoparticles through the blood brain barrier (BBB)

Cited by 97 publications

References 43 publications

Overcoming the Blood–Brain Barrier. Challenges and Tricks for CNS Drug Delivery

Overcoming the Blood–Brain Barrier. Challenges and Tricks for CNS Drug Delivery

<p>Intranasal Delivery of Immunotherapeutic Nanoformulations for Treatment of Glioma Through in situ Activation of Immune Response</p>

Design of Gold Nanoparticles in Dendritic Cell‐Based Vaccines

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