Intracellularly Acid-Switchable Multifunctional Micelles for Combinational Photo/Chemotherapy of the Drug-Resistant Tumor

doi:10.1021/acsnano.5b07706

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	Intracellularly Acid-Switchable Multifunctional Micelles for Combinational Photo/Chemotherapy of the Drug-Resistant Tumor
	Wang, Tingting 1,2; Wang, Dangge 1,2; Yu, Haijun1,2 ; Wang, Mingwei3 ; Liu, Jianping 1,2; Feng, Bing 1,2; Zhou, Fangyuan 1,2; Yin, Qi1,2 ; Zhang, Zhiwen1,2 ; Huang, Yongzhuo1,2
刊名	ACS NANO
	2016-03
卷号	10 期号:3 页码:3496-3508
关键词	acid-switchable micelles drug resistance tissue penetration combinational therapy multimodal imaging
ISSN号	1936-0851
DOI	10.1021/acsnano.5b07706
文献子类	Article
英文摘要	The intrinsic or acquired drug resistance is the main challenge for cancer chemotherapy today. So far, many nanosized drug delivery systems (NDDS) have been exploited to combat cancer drug resistance. However, the therapy efficacy of current NDDS is severely impaired by the limited tumor penetration of the nanoparticles due to the existence of physiological and pathological barriers in the solid tumor. In this study, we report on the design and fabrication of intracellularly acid-switchable multifunctional micelles for combinational photo- and chemotherapy of the drug-resistant tumor. The micelles were composed of a pH-responsive diblock copolymer, a photosensitizer, and a polymeric prodrug of doxorubicin. The micelle displayed silenced fluorescence and photoactivity during the blood circulation and switched to an active state in weakly acid conditions (i.e., pH <= 6.2) in the endocytic vesicles to dramatically induce a 7.5-fold increase of the fluorescence signal for fluorescence imaging. Upon near-infrared (NIR) laser irradiation, the micelle induced notable reactive oxygen species generation to trigger cytosol release of the chemotherapeutics and perform photodynamic therapy (PDT). Moreover, the micelle efficiently converted the MR light to local heat for enhancing tumor penetration of the anticancer drug, tumor specific photothermal therapy, and photoacoustic (PA) imaging. Furthermore, the micelles could generate amplified magnetic resonance (MR) signal in an acidic microenvironment to perform MR imaging. Collectively, this study presents a robust nanoplatform for multimodal imaging and combinational therapy of the drug-resistant tumor, which might provide an insight for developing polymer based NDDS for cancer therapy.
资助项目	National Basic Research Program of China[2013CB932704] ; National Natural Science Foundation of China[81521005] ; National Natural Science Foundation of China[81373359] ; National Natural Science Foundation of China[11275050] ; Youth Innovation Promotion Association CAS[00000000]
WOS关键词	SIRNA DELIVERY ; CANCER-THERAPY ; POLYMERIC MICELLES ; NANOPARTICLES ; NANOMEDICINE ; TOMOGRAPHY ; NANOMATERIALS ; ACCUMULATION ; THERANOSTICS ; NANOPLATFORM
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:000372855400052
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276114]
专题	药物制剂研究中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Yu, Haijun; Li, Yaping
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Fudan Univ, Shanghai Canc Ctr, Dept Nucl Med, Shanghai 200032, Peoples R China
推荐引用方式 GB/T 7714	Wang, Tingting,Wang, Dangge,Yu, Haijun,et al. Intracellularly Acid-Switchable Multifunctional Micelles for Combinational Photo/Chemotherapy of the Drug-Resistant Tumor[J]. ACS NANO,2016,10(3):3496-3508.
APA	Wang, Tingting.,Wang, Dangge.,Yu, Haijun.,Wang, Mingwei.,Liu, Jianping.,...&Li, Yaping.(2016).Intracellularly Acid-Switchable Multifunctional Micelles for Combinational Photo/Chemotherapy of the Drug-Resistant Tumor.ACS NANO,10(3),3496-3508.
MLA	Wang, Tingting,et al."Intracellularly Acid-Switchable Multifunctional Micelles for Combinational Photo/Chemotherapy of the Drug-Resistant Tumor".ACS NANO 10.3(2016):3496-3508.