A nanoformulation for the preferential accumulation in adult neurogenic niches

JOURNAL OF CONTROLLED RELEASE

卷:284

Article

Praca, Catarina^1,3  Rai, Akhilesh²  Santos, Tiago⁵  Cristovao, Ana C.⁵  Pinho, Sonia L.²  Cecchelli, Romeo³  Dehouck, Marie-Pierre³  Bernardino, Liliana⁵  Ferreira, Lino S.^2,4 

[1] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, Inst Interdisciplinary Res IIIUC, Doctoral Programme Expt Biol & Biomed PDBEB, Coimbra, Portugal

[2] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, Coimbra, Portugal

[3] Univ Artois, Fac Sci Jean Perrin, Lens, France

[4] Univ Coimbra, Fac Med, Coimbra, Portugal

[5] Univ Beira Interior, Hlth Sci Res Ctr, Fac Hlth Sci, P-6201506 Covilha, Portugal

关键词: Blood-brain barrier;    Nanoparticles;    Nanorods;    NIR laser;    Brain targeting;    Neurogenic niches;   

DOI  :  10.1016/j.jconrel.2018.06.013

来源: Elsevier

【 摘 要 】

Stimulation of adult neurogenesis by targeting the endogenous neural stem cells (NSCs), located in hippocampus and subventricular zone (SVZ), with nanoformulations has been proposed for brain repair in cases of neurodegenerative diseases. Unfortunately, it is relatively unknown the nanoformulation properties to facilitate their accumulation in the neurogenic niches after intravenous injection. Here, we have screened different gold-based formulations having variable morphology, surface chemistry and responsiveness to light for their capacity to cross the blood brain barrier (BBB) and accumulate preferentially in the neurogenic niches. Results obtained in a human in vitro BBB model showed that gold nanoparticles (Au NPs) and gold nanorods (Au NRs) conjugated with medium density of transferrin (Tf) peptides (i.e. between 169 and 230 peptides per NP) crossed more efficiently the BBB than the remaining formulations. This is due to a relatively lower avidity of these formulations to Tf receptor (TfR) and lower accumulation in the lysosomes, as compared to the other formulations. We further show that the near infrared light (NIR) irradiation of Au NRs, under a certain concentration and at specific cell culture time, lead to the opening of the BBB. Finally, we demonstrate that Au NRs conjugated with Tf administered intravenously in mice and activated by NIR had the highest accumulation in the neurogenic niches. Our results open the possibility of targeting more effectively the neurogenic niches by controlling the properties of the nanoformulations.

【 授权许可】

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