Improving gold nanorod delivery to the central nervous system by conjugation to the shuttle Angiopep-2

被引:39
作者
Velasco-Aguirre, Carolina [1 ]
Morales-Zavala, Francisco [1 ]
Salas-Huenuleo, Edison [1 ]
Gallardo-Toledo, Eduardo [1 ]
Andonie, Oscar [2 ]
Munoz, Luis [2 ]
Rojas, Ximena [2 ]
Acosta, Gerardo [3 ,4 ]
Sanchez-Navarro, Macarena [5 ]
Giralt, Ernest [3 ]
Araya, Eyleen [6 ]
Albericio, Fernando [3 ,4 ,7 ]
Javier Kogan, Marcelo [1 ]
机构
[1] Univ Chile, Adv Ctr Chron Dis ACCDiS, Fac Ciencias Quim & Farmaceut, Dept Quim Farmacol & Toxicol, Santiago, Chile
[2] CCHEN, Comis Chilena Energia Nucl, Secc Metrol Quim, Nueva Bilbao 12501, Santiago, Chile
[3] Univ Barcelona, Dept Inorgan & Organ Chem, Marti i Franques 1, E-08028 Barcelona, Spain
[4] CIBER BBN, Networking Ctr Bioengn Biomat & Nanomed, Barcelona Sci Pk, Barcelona 08028, Spain
[5] Barcelona Inst Sci & Technol, Inst Res Biomed IRB Barcelona, Baldiri Reixac 10, Barcelona 08028, Spain
[6] Univ Andres Bello, Fac Ciencias Exactas, Dept Ciencias Quim, Republica 275, Santiago 8370146, Chile
[7] Univ KwaZulu Natal, Sch Chem & Phys, ZA-4001 Durban, South Africa
关键词
angiopep-2; blood-brain barrier; drug delivery; gold nanoparticle; gold nanorods; photothermal effect; theranostics; BRAIN DELIVERY; POLY(ETHYLENE GLYCOL); NANOPARTICLES; PEPTIDE; PROTEIN; DRUG; DOXORUBICIN; BIODISTRIBUTION; STABILITY; TRANSPORT;
D O I
10.2217/nnm-2017-0181
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Aim: To improve the in vivo delivery of gold nanorods (GNRs) to the central nervous system of rats, these gold nanoparticles were conjugated to Angiopep-2, a shuttle peptide that can cross the blood-brain barrier. Materials & methods: GNRs were synthesized and modified using polyethylene glycol and Angiopep-2 (GNR-PEG-Angiopep-2). The physicochemical properties, in vitro cytotoxicity and ex vivo biodistribution of the conjugate were examined. Results: GNR-PEG-Angiopep-2 was stable over the following days, and the different concentrations that were tested did not affect the viability of microvascular endothelial cells. The conjugation of Angiopep-2 to GNRs enhanced the endocytosis of these particles (in vitro) and the accumulation in brains (in vivo), when compared with GNRs modified only with PEG. Conclusion: This study provides evidence that Angiopep-2 improves the delivery of GNRs to the brain parenchyma. This property is highly relevant for future applications of GNRs as platforms for photothermal and theranostic purposes.
引用
收藏
页码:2503 / 2517
页数:15
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