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	Enzyme-sensitive cytotoxic peptide-dendrimer conjugates enhance cell apoptosis and deep tumor penetration
	Liu, Fu-Hua1,2; Hou, Chun-Yuan2; Zhang, Di2; Zhao, Wen-Jing1,2; Cong, Yong2; Duan, Zhong-Yu1; Qiao, Zeng-Ying1,2; Wang, Hao1,2
刊名	Biomaterials science
	2018-03-01
卷号	6期号:3页码:604-613
ISSN号	2047-4830
DOI	10.1039/c7bm01182b
通讯作者	Duan, zhong-yu(zyduan@hebut.edu.cn) ; Qiao, zeng-ying(qiaozy@nanoctr.cn) ; Wang, hao(wanghao@nanoctr.cn)
英文摘要	Peptide nanodrugs have been developed as promising antitumor chemotherapeutics because they partially overcome the drawbacks of free peptide drugs, but insufficient tumor penetration and interference of peptide function limit their further application. in this work, we have developed multifunctional peptide conjugated dendrimers for improving tumor penetration, cancer cell-specific peptide delivery and anticancer ability. the cytotoxic peptide klak, cell-penetrating peptide tat and matrix metalloproteinase 2 (mmp2)-sensitive peptide-poly(ethylene glycol) (peg) were conjugated onto dendrimers by one-pot synthesis to gain pkt-s-peg. the enzyme-sensitive properties and incubation stability of the dendrimers were investigated by dynamic light scattering (dls) and transmission electron microscopy (tem). moreover, the cell viability, internalization pathway, mitochondria-regulated apoptosis and tumor penetration ability were measured by cck-8 assay, lysosome colocalization, jc-1 assay and multicellular spheroid (mcs) experiments, respectively, in human primary glioblastoma (u87) cells. pkt-s-peg showed significantly enhanced intracellular delivery performance, antitumor efficacy and deep tumor penetration capacity compared to a control non-mmp2 sensitive dendrimer pkt-c-peg. the mmp2-over expressing tumor microenvironment caused deprotection by removal of peg, resulting in the decrease of particle size and exposure of klak and tat, which enhanced tumor penetration, the entry of bioactive peptides into cells and subsequently the effective disruption of mitochondria. we believe that the peptide-dendrimer conjugate has potential for specific and effective delivery of peptide-based therapeutics into tumors.
WOS关键词	TARGETED DRUG-DELIVERY ; MESOPOROUS SILICA NANOPARTICLES ; CANCER-THERAPY ; BREAST-CANCER ; MATRIX METALLOPROTEINASES ; POLYMERIC NANOPARTICLES ; BIOMEDICAL APPLICATIONS ; PHOTOTHERMAL THERAPY ; ANTICANCER ACTIVITY ; IN-VIVO
WOS研究方向	Materials Science
WOS类目	Materials Science, Biomaterials
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000426392200014
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2178091
专题	高能物理研究所
通讯作者	Duan, Zhong-Yu; Qiao, Zeng-Ying; Wang, Hao
作者单位	1.Hebei Univ Technol, Sch Chem Engn & Technol, Tianjin 300130, Peoples R China 2.Natl Ctr Nanosci & Technol NCNST, CAS Key Lab Biomed Effects Nanomat & Nanosafety, CAS Ctr Excellence Nanosci, Beijing 100190, Peoples R China
推荐引用方式 GB/T 7714	Liu, Fu-Hua,Hou, Chun-Yuan,Zhang, Di,et al. Enzyme-sensitive cytotoxic peptide-dendrimer conjugates enhance cell apoptosis and deep tumor penetration[J]. Biomaterials science,2018,6(3):604-613.
APA	Liu, Fu-Hua.,Hou, Chun-Yuan.,Zhang, Di.,Zhao, Wen-Jing.,Cong, Yong.,...&Wang, Hao.(2018).Enzyme-sensitive cytotoxic peptide-dendrimer conjugates enhance cell apoptosis and deep tumor penetration.Biomaterials science,6(3),604-613.
MLA	Liu, Fu-Hua,et al."Enzyme-sensitive cytotoxic peptide-dendrimer conjugates enhance cell apoptosis and deep tumor penetration".Biomaterials science 6.3(2018):604-613.

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