Blood-Brain-Barrier-Penetrating Albumin Nanoparticles for Biomimetic Drug Delivery via Albumin-Binding Protein Pathways for Antiglioma Therapy

doi:10.1021/acsnano.6b04268

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	Blood-Brain-Barrier-Penetrating Albumin Nanoparticles for Biomimetic Drug Delivery via Albumin-Binding Protein Pathways for Antiglioma Therapy
	Lin, Tingting 2,3,4; Zhao, Pengfei 1,2; Jiang, Yifan 2; Tang, Yisi 2; Jin, Hongyue 2; Pan, Zhenzhen 2; He, Huining 3; Yang, Victor C.3,5; Huang, Yongzhuo2
刊名	ACS NANO
	2016-11
卷号	10 期号:11 页码:9999-10012
关键词	albumin nanoparticle albumin-binding protein brain tumor targeting SPARC gp60 cell-penetrating peptide biomimetic delivery
ISSN号	1936-0851
DOI	10.1021/acsnano.6b04268
文献子类	Article
英文摘要	Nutrient transporters have been explored for biomimetic delivery targeting the brain. The albumin-binding proteins (e.g., SPARC and gp60) are overexpressed in many tumors for transport of albumin as an amino acid and an energy source for fast-growing cancer cells. However, their application in brain delivery has rarely been investigated. In this work, SPARC and gp60 overexpression was found on glioma and tumor vessel endothelium; therefore, such pathways were explored for use in brain-targeting biomimetic delivery. We developed a green method for blood-brain barrier (BBB)-penetrating albumin nanoparticle synthesis, with the capacity to coencapsulate different drugs and no need for cross-linkers. The hydrophobic drugs (i.e., paclitaxel and fenretinide) yield synergistic effects to induce albumin self-assembly, forming dual drug loaded nanoparticles. The albumin nanoparticles can penetrate the BBB and target glioma cells via the mechanisms of SPARC- and gp60-mediated biomimetic transport. Importantly, by modification with the cell-penetrating peptide LMWP, the albumin nanoparticles display enhanced BBB penetration, intratumoral infiltration, and cellular uptake. The LMWP-modified nanoparticles exhibited improved treatment outcomes in both subcutaneous and intracranial glioma models, with reduced toxic side effects. The therapeutic mechanisms were associated with induction of apoptosis, antiangiogenesis, and tumor immune microenvironment regulation. It provides a facile method for dual drug-loaded albumin nanoparticle preparation and a promising avenue for biomimetic delivery targeting the brain tumor based on combination therapy.
资助项目	National Basic Research Program of China (973 Program)[2013CB932503] ; National Basic Research Program of China (973 Program)[2014CB931900] ; NSFC, China[81172996] ; NSFC, China[81373357] ; NSFC, China[81422048] ; NSFC, China[81673382] ; NSFC, China[81521005] ; NSFC, China[81361140344]
WOS关键词	SOLID TUMORS ; ENDOTHELIAL-CELLS ; GENE DELIVERY ; CANCER ; PEPTIDES ; EXPRESSION ; PACLITAXEL ; RECEPTOR ; TAT
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000388913100028
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275829]
专题	药物制剂研究中心
通讯作者	Huang, Yongzhuo
作者单位	1.Nanchang Univ, Coll Pharm, 461 Bayi Rd, Nanchang 330006, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China; 3.Tianjin Med Univ, Tianjin Key Lab Technol Enabling Dev Clin Therape, Sch Pharm, Tianjin 300070, Peoples R China; 4.Binzhou Med Univ Hosp, Dept Pharm, 661 Huanghe Rd, Binzhou 256603, Peoples R China; 5.Univ Michigan, Coll Pharm, 428 Church St, Ann Arbor, MI 48108 USA
推荐引用方式 GB/T 7714	Lin, Tingting,Zhao, Pengfei,Jiang, Yifan,et al. Blood-Brain-Barrier-Penetrating Albumin Nanoparticles for Biomimetic Drug Delivery via Albumin-Binding Protein Pathways for Antiglioma Therapy[J]. ACS NANO,2016,10(11):9999-10012.
APA	Lin, Tingting.,Zhao, Pengfei.,Jiang, Yifan.,Tang, Yisi.,Jin, Hongyue.,...&Huang, Yongzhuo.(2016).Blood-Brain-Barrier-Penetrating Albumin Nanoparticles for Biomimetic Drug Delivery via Albumin-Binding Protein Pathways for Antiglioma Therapy.ACS NANO,10(11),9999-10012.
MLA	Lin, Tingting,et al."Blood-Brain-Barrier-Penetrating Albumin Nanoparticles for Biomimetic Drug Delivery via Albumin-Binding Protein Pathways for Antiglioma Therapy".ACS NANO 10.11(2016):9999-10012.