Reconfigurable Peptide Nanotherapeutics at Tumor Microenvironmental pH

doi:10.1021/acsami.7b09033

	Reconfigurable Peptide Nanotherapeutics at Tumor Microenvironmental pH
	Gao, YJ; Cong, Y; Zhao, LN; Hu, ZY; Wang, H; Zhao LN(赵丽娜); Qiao, ZY; Zhao, WJ
刊名	ACS APPLIED MATERIALS & INTERFACES
	2017
卷号	9 期号:36 页码:30426-30436
关键词	peptide reconfiguration pH-sensitive MMP nanotherapeutics
ISSN号	1944-8244
DOI	10.1021/acsami.7b09033
文献子类	Article
英文摘要	Peptide nanomaterials have recently attracted considerable interest in the biomedical field. However, their poor bioavailability and less powerful therapeutic efficacy hamper their further applications. Herein, we discovered reconfigurable and activated nanotherapeutics in the tumor microenvironment. Two peptides, that is, a pH-responsive peptide HLAH and a matrix metalloprotease-2 (MMP2)-sensitive peptide with a poly(ethylene glycol) (PEG) terminal were conjugated onto the hydrophobic poly(beta-thioester)s backbones to gain the copolymer PSH. The therapeutic activity of the HLAH peptide could be activated in tumors owing to its reconfiguration under microenvironmental pH. The resultant copolymers self-assembled into nanoparticles under physiological condition, with HLAH in cores protected by PEG shells. The moderate size (similar to 100 nm) and negative potential enabled the stable circulation of PSH in the bloodstream. Once arrived at the tumor site, the PSH nanoparticles were stimulated by overexpressed MMP2 and acidic pH, and subsequently the shedding of the PEG shell and protonation of the HLAH peptide induced the reassembly of nanoparticles, resulting in the formation of nanoparticles with activated cytotoxic peptides on the surface. In vivo experiments demonstrated that the reorganized nanoassembly contained three merits: (1) effective accumulation in the tumor site, (2) enhanced antitumor capacity, and (3) no obvious toxic effect at the treatment dose. This on-site reorganization strategy provides an avenue for developing high-performance peptide nanomaterials in cancer treatment.
WOS关键词	DRUG-DELIVERY ; ANTICANCER ACTIVITY ; MOLECULAR-DYNAMICS ; SYSTEMIC TOXICITY ; IN-VIVO ; PHYSICOCHEMICAL CHARACTERISTICS ; PHOTODYNAMIC THERAPY ; NANOPARTICLES ; CHARGE ; REVERSAL
WOS研究方向	Science & Technology - Other Topics ; Materials Science
语种	英语
WOS记录号	WOS:000411043600021
内容类型	期刊论文
源URL	[http://ir.ihep.ac.cn/handle/311005/285273]
专题	高能物理研究所_多学科研究中心
作者单位	中国科学院高能物理研究所
推荐引用方式 GB/T 7714	Gao, YJ,Cong, Y,Zhao, LN,et al. Reconfigurable Peptide Nanotherapeutics at Tumor Microenvironmental pH[J]. ACS APPLIED MATERIALS & INTERFACES,2017,9(36):30426-30436.
APA	Gao, YJ.,Cong, Y.,Zhao, LN.,Hu, ZY.,Wang, H.,...&Zhao, WJ.(2017).Reconfigurable Peptide Nanotherapeutics at Tumor Microenvironmental pH.ACS APPLIED MATERIALS & INTERFACES,9(36),30426-30436.
MLA	Gao, YJ,et al."Reconfigurable Peptide Nanotherapeutics at Tumor Microenvironmental pH".ACS APPLIED MATERIALS & INTERFACES 9.36(2017):30426-30436.