A pH-responsive natural cyclopeptide RA-V drug formulation for improved breast cancer therapy

doi:10.1039/c5tb00445d

	A pH-responsive natural cyclopeptide RA-V drug formulation for improved breast cancer therapy
	Qiao, Zeng-Ying; Zhang, Di; Hou, Chun-Yuan; Zhao, Si-Meng; Liu, Ya; Gao, Yu-Juan; Tan, Ning-Hua; Wang, Hao; Wang,H (reprint author),Natl Ctr Nanoscience & Technol NCNST,CAS Key Lab Biol Effects Nanomat & Nanosafety,Beijing 100190,Peoples R China.; nhtan@mail.kib.ac.cn; wanghao@nanoctr.cn
	2015
发表期刊	JOURNAL OF MATERIALS CHEMISTRY B
卷号	3 期号:22 页码:4514-4523
摘要	The natural plant cyclopeptide RA-V, which was isolated from the roots of Rubia yunnanensis, was discovered to be a novel anti-cancer candidate. However, the cyclic hexapeptide exhibited poor solubility in physiological conditions, limiting its application for cancer therapy in vivo. To solve this problem, pH-sensitive polymers were developed for targeted RA-V delivery into tumor sites and for acid-triggered drug release. The poly(beta-amino ester)s (PAE) copolymers self-assembled into micelle-like nanoparticles in an aqueous solution at pH 7.4, and the solubility of RA-V was enhanced by loading the drug into the hydrophobic cores of micelles. The near-infrared (NIR) fluorescent probe squaraine (SQ) dye, as an imaging probe, could also be encapsulated into polymer micelles simultaneously. The diameters of the RA-V/SQ loaded micelles were measured by dynamic light scattering (DLS) and transmission electron microscopy (TEM), which proved that the micelles with sizes of 35-60 nm were suitable as anti-cancer drug nano-vehicles. The drug-loading capacity and drug release profiles of RA-V-loaded micelles were calculated and monitored by high performance liquid chromatography (HPLC) measurements. The RA-V/SQ loaded micelles were stable at a neutral pH, and drug release could be greatly accelerated by the acid-triggered ionization of copolymer chains. Similarly, with free RA-V cyclopeptide, the RA-V/SQ loaded micelles exhibited high anti-cancer efficiency toward MCF-7 cells and Hela cells, while the intact polymer micelles and SQ-loaded micelles are non-toxic. Moreover, the endocytosis pathway and mitochondria-regulated apoptosis of RA-V/SQ loaded micelles were proved by lysosome colocalization and JC-1 assay, respectively. Finally, biodistribution and tumor growth inhibition were evaluated in MCF-7 cell-xenografted nude mice, demonstrating that RA-V/SQ loaded micelles could realize tumor imaging and effectively and simultaneously inhibit tumor growth. Therefore, the RA-V/SQ loaded micelles may find use as potential nano-scaled cancer therapeutics and imaging agents.
学科领域	Materials Science, bioMaterials
DOI	10.1039/c5tb00445d
收录类别	SCI
语种	英语
WOS记录号	WOS:000355560400005
引用统计	被引频次：20[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/21354
专题	植物化学与西部植物资源持续利用国家重点实验室
通讯作者	Wang,H (reprint author),Natl Ctr Nanoscience & Technol NCNST,CAS Key Lab Biol Effects Nanomat & Nanosafety,Beijing 100190,Peoples R China.; nhtan@mail.kib.ac.cn; wanghao@nanoctr.cn
推荐引用方式 GB/T 7714	Qiao, Zeng-Ying,Zhang, Di,Hou, Chun-Yuan,et al. A pH-responsive natural cyclopeptide RA-V drug formulation for improved breast cancer therapy[J]. JOURNAL OF MATERIALS CHEMISTRY B,2015,3(22):4514-4523.
APA	Qiao, Zeng-Ying.,Zhang, Di.,Hou, Chun-Yuan.,Zhao, Si-Meng.,Liu, Ya.,...&wanghao@nanoctr.cn.(2015).A pH-responsive natural cyclopeptide RA-V drug formulation for improved breast cancer therapy.JOURNAL OF MATERIALS CHEMISTRY B,3(22),4514-4523.
MLA	Qiao, Zeng-Ying,et al."A pH-responsive natural cyclopeptide RA-V drug formulation for improved breast cancer therapy".JOURNAL OF MATERIALS CHEMISTRY B 3.22(2015):4514-4523.

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