Functional Protein Delivery into Neurons Using Polymeric Nanoparticles

Hasadsri, Linda; Kreuter, Jörg; Hashimoto, Hiroaki; Iwasaki, Takashi; George, Julia M.

doi:10.1074/jbc.m805956200

Cited by 121 publications

(74 citation statements)

References 75 publications

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“…Moreover, SK-N-SH-CP cells are disabled for expression of IFN-␤ and possess a modified form of Tolllike receptor 3 (26). It is well known that delivery of proteins/ peptides or other macromolecules into neurons can be difficult, possibly in relation to their differentiated state (17,49). Accordingly, P60-Tat uptake was observed neither in SK-N-SH nor in SK-N-SH CP cells (data not shown).…”

Section: Vol 83 2009 Anti-rabv Activity Of Phosphoprotein-derived Pmentioning

confidence: 87%

Peptides That Mimic the Amino-Terminal End of the Rabies Virus Phosphoprotein Have Antiviral Activity

Castel

Chtéoui

Caignard

et al. 2009

J Virol

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We wanted to develop a therapeutic approach against rabies disease by targeting the lyssavirus transcription/replication complex. Because this complex (nucleoprotein N-RNA template processed by the L polymerase and its cofactor, the phosphoprotein P) is similar to that of other negative-strand RNA viruses, we aimed to design broad-spectrum antiviral drugs that could be used as a complement to postexposure vaccination and immunotherapy. Recent progress in understanding the structure/function of the rabies virus P, N, and L proteins predicts that the amino-terminal end of P is an excellent target for destabilizing the replication complex because it interacts with both L (for positioning onto the N-RNA template) and N (for keeping N soluble, as needed for viral RNA encapsidation). Thus, peptides mimicking various lengths of the aminoterminal end of P have been evaluated, as follows: (i) for binding properties to the N-P-L partners by the two-hybrid method; (ii) for their capacity to inhibit the transcription/replication of a rabies virus minigenome encoding luciferase in BHK-21-T7 cells; and (iii) for their capacity to inhibit rabies virus infection of BHK-21-T7 cells and of two derivatives of the neuronal SK-N-SH cell line. Peptides P60 and P57 (the first 60 and first 57 NH 2 residues of P, respectively) exhibited a rapid, strong, and long-lasting inhibitory potential on luciferase expression (>95% from 24 h to 55 h). P42 was less efficient in its inhibition level (75% for 18 to 30 h) and duration (40% after 48 h). The most promising peptides were synthesized in tandem with the Tat sequence, allowing cell penetration. Their inhibitory effects were observed on BHK-21-T7 cells infected with rabies virus and Lagos bat virus but not with vesicular stomatitis virus. In neuronal cells, a significant inhibition of both nucleocapsid inclusions and rabies virus release was observed.

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Section: Vol 83 2009 Anti-rabv Activity Of Phosphoprotein-derived Pmentioning

confidence: 87%

Peptides That Mimic the Amino-Terminal End of the Rabies Virus Phosphoprotein Have Antiviral Activity

Castel

Chtéoui

Caignard

et al. 2009

J Virol

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“…Figure 11: Possible Mechanism of Apo E-functionalized Nanodroplets uptake in brain. [16] The present studies possibly presume the assumption that polysorbate-80 coated CSEDD could improve brain specific delivery due to the high affinity to adsorb plasma apolipoproteins on the surface, followed by low-density lipoprotein (LDL) receptor recognition and uptake by endothelial cells lining brain capillaries [27]. Moreover, the employment of apolipoprotein fractions containing only a binding sequence appears to be sufficient [28][29][30][31].…”

Section: Discussionmentioning

confidence: 99%

Brain Targeting Potential of Intravenous Carbamazepine SNEDDS

Kumar¹,

Rambhau²

2017

J Mol Pharm Org Process Res

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Purpose: The objective of this study was to evaluate the ability of nano-droplets of Self Nano Emulsifying Drug Delivery System to diffuse into the brain tissue. Methods:The preconcentrate was prepared by dissolving oils, surfactants and cosolvents in 1:1 mixture of methanol and chloroform and flash evaporated at 50°C and was stored at room temperature until their use in subsequent studies. CSEDD with surfactant polysorbate-80 were radiolabelled with radioactive C18 triglyceride. The nanodroplets formed by CSEDD in 5% dextrose were subjected to evaluation in blood and brain. Results:The intravenous pharmacokinetics of carbamazepine in rats of CSEDD formulation generated high initial serum levels (5.25 mcg/ml) at 0.25 h when compared to C-Sol (3.91 mcg/ml) at 0.5 h. It was found that oil to surfactant ratio had an impact on the physical characteristics of the nano-emulsion formed. The brain levels of CBZ from optimized CSEDD were significantly high at all-time points when compared to plain solution. The initial levels of CBZ from CSEDD was 8.023 mcg/ml thereafter the levels were consistently high till 8 h and the initial levels of CBZ from plain solution was 3.62 mcg/ml followed by a gradual decline till 4 h evidently showing that the clearance of CBZ from CSEDD was reduced. The brain targeting index of CSEDD and solution were 3 and 2 respectively. The brain enhancement factor value was found to be 22.29 at 15 min revealing a very rapid penetration of CBZ into brain. Conclusions:This study proposes intravenous CSEDD as a new brain delivery system and highlights two requirements to design adequate delivery systems for long circulating properties of the carrier and appropriate surface characteristics to allow interactions with BBB endothelial cells.

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“…52 Nanoparticles composed of poly(n-butyl cyanoacrylate) coated with the surfactant polysorbate 80 can bypass the BBB by binding to apolipoprotein E followed by adhesion and receptormediated transcytosis via the low-attenuation lipoprotein receptor present on BBB endothelial cells. 53,54 This phenomenon has the potential to allow in vivo molecular imaging. Studies describing nanocarriers traversing the BBB have, in large part, relied on postmortem analysis; however, recently the delivery of BBB impermeable molecular imaging contrast agents for in vivo microscopy and MR imaging has been performed.…”

Section: Enhanced Brain Delivery Of Blood-brain Barrier Impermeable Pmentioning

confidence: 99%

New Applications of Nanotechnology for Neuroimaging

Suffredini

East

Levy

2013

AJNR Am J Neuroradiol

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SUMMARY:Advances in nanotechnology have the potential to dramatically enhance the detection of neurologic diseases with targeted contrast agents and to facilitate the delivery of focused therapies to the central nervous system. We present the physicochemical rationale for their use, applications in animal models, and ongoing clinical trials using these approaches. We highlight advances in the use of nanoparticles applied to brain tumor imaging, tumor angiogenesis, neurodegeneration, grafted stem cells, and neuroprogenitor cells.ABBREVIATIONS: amyloid beta ϭ A␤; NO ϭ nitric oxide; NOS ϭ nitric oxide synthase; PBCA ϭ poly(n-butyl cyanoacrylate); QDots ϭ quantum dots; SPIO ϭ

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Functional Protein Delivery into Neurons Using Polymeric Nanoparticles

Cited by 121 publications

References 75 publications

Peptides That Mimic the Amino-Terminal End of the Rabies Virus Phosphoprotein Have Antiviral Activity

Peptides That Mimic the Amino-Terminal End of the Rabies Virus Phosphoprotein Have Antiviral Activity

Brain Targeting Potential of Intravenous Carbamazepine SNEDDS

New Applications of Nanotechnology for Neuroimaging

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