Transport Mechanisms of Squalenoyl-Adenosine Nanoparticles Across the Blood-Brain Barrier

被引：33

作者：

Gaudin, Alice ^{[1
]}

Tagit, Oya ^{[3
]}

Sobot, Dunja ^{[1
]}

Lepetre-Mouelhi, Sinda ^{[1
]}

Mougin, Julie ^{[1
]}

Martens, Thomas F. ^{[4
,5
]}

Braeckmans, Kevin ^{[4
,5
]}

Nicolas, Valerie ^{[2
]}

Desmaele, Didier ^{[1
]}

de Smedt, Stefaan C. ^{[4
]}

Hildebrandt, Niko ^{[3
]}

Couvreur, Patrick ^{[1
]}

Andrieux, Karine ^{[1
]}

机构：

[1] Univ Paris 11, Fac Pharm, Inst Gallen Paris Sud, UMR CNRS 8612, F-92296 Chatenay Malabry, France

[2] Univ Paris 11, Fac Pharm, Inst Innovat Therapeut, ITFM IFR141, F-92296 Chatenay Malabry, France

[3] Univ Paris 11, Inst Elect Fondamentale, NanoBioPhoton, F-91405 Orsay, France

[4] Univ Ghent, Fac Sci, Lab Gen Biochem & Phys Pharm, B-9000 Ghent, Belgium

[5] Univ Ghent, Ctr Nano & Biophoton, B-9000 Ghent, Belgium

来源：

CHEMISTRY OF MATERIALS | 2015年 / 27卷 / 10期

基金：

欧洲研究理事会;

关键词：

ENDOTHELIAL-CELL LINE; RECEPTOR-MEDIATED ENDOCYTOSIS; RESONANCE ENERGY-TRANSFER; IN-VITRO; DRUG-DELIVERY; PROTEIN; MODEL; NANOMEDICINES; TRANSCYTOSIS; MICROSCOPY;

D O I：

10.1021/acs.chemmater.5b00267

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

Drug delivery to the brain is one of the major challenges in the treatment of cerebral diseases and implies extensive understanding of nanomedicine transcytosis pathways across the blood brain barrier (BBB). In this study, we investigated the interaction of squalenoyl-adenosine nano-assemblies (SQAd NAs) with human brain endothelial cells, concerning their endocytotic pathway using chemical inhibitors and nanostructure integrity using Forster resonance energy transfer (FRET). Practically, SQAd NAs were labeled with two different organic dyes as a donor acceptor FRET pair to form FRET SQAd NAs with diameters of ca. 120 nm. Using the human cerebral endothelial cell line, hCMEC/D3, as a well-recognized BBB model, we demonstrated that the NAs were internalized mainly by LDL receptors-mediated endocytosis, then progressively disassembled inside the cells, and finally exocytosed as single molecules. These observations allow explaining the previously described pharmacological efficiency of the SQAd NAs in both a cerebral ischemia model and a spinal cord injury model, confirming that the endothelial cells of the neurovascular unit may represent a very promising therapeutic target for the treatment of certain neurological diseases.

引用

页码：3636 / 3647

页数：12

共 55 条

[41] Internal benchmarking of a human blood-brain barrier cell model for screening of nanoparticle uptake and transcytosis [J].