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The modulation of tumor vessel permeability by thalidomide and its impacts on different types of targeted drug delivery systems in a sarcoma mouse model
Wang, Dan1,2; Fu, Jijun1,2; Shi, Yujie1,2; Peng, Dong3; Yuan, Lan4; He, Bing1,2; Dai, Wenbing1,2; Zhang, Hua1,2; Wang, Xueqing1,2; Tian, Jie3; Zhang, Qiang1,2
2016-09-28
发表期刊JOURNAL OF CONTROLLED RELEASE
卷号238页码:186-196
文章类型Article
摘要The transport of nanocarriers is supposed to be based on EPR effect which is affected by diverse factors, so the modulation of EPR effect seems very significant for nanocarriers including targeted drug delivery systems (TDDSs). Besides, it is extremely unclear how the EPR effect impacts the fate of different types of TDDSs. To make the most advantage of EPR effect for TDDSs, it is definitely necessary to clarify these key issues. Here, we construct and characterize various TDDSs, including sterically-stabilized liposomes (SSL), RGD functionalized SSL (RGD-SSL) and novel 7PEP functionalized SSL (7PEP-SSL), loaded with doxorubicin (DOX), DIR or DID. Here, we modulate the permeability of tumor vessels by thalidomide (THD) in a sarcoma-bearing EPR mouse model via monitoring endogenous deoxygenated hemoglobin in circulation, and then we confirm the effect of THD on tumor vessel permeability by vessel density, vessel maturity, VEGF expression and so on. Importantly, we investigate and find the impacts of EPR effect on the antitumor efficacy, in vivo distribution and intratumoral microdistribution of the three TDDSs. Interestingly, the EPR effects affect different TDDSs differently. The elevated EPR effect enhances the tumor accumulation of SSL and RGD-SSL but fails to increase their efficacy. The RGD-SSL exhibits the best efficacy with the least fluctuation, demonstrating the advantage of angiogenesis targeted systems. 7PEP-SSL seems the biggest beneficiary of EPR effect, suggesting the significance of EPR modulation for cells targeted systems. Generally, this study demonstrates the feasibility of modulating EPR effect bidirectionally by THD as well as the impacts of EPR effect on different type of testing TDDSs based on this animal model. It certainly provides novel insight into the design and potential use of TDDSs. (C) 2016 Elsevier B.V. All rights reserved.
关键词Targeted Drug Delivery Systems Animal Model Of Epr Effect Tumor Vessel Permeability Thalidomide Antitumor Efficacy Distribution
WOS标题词Science & Technology ; Physical Sciences ; Life Sciences & Biomedicine
DOI10.1016/j.jconrel.2016.07.014
关键词[WOS]MACROMOLECULAR THERAPEUTICS ; TRANSFERRIN RECEPTOR ; VASCULAR-PERMEABILITY ; CANCER-CHEMOTHERAPY ; BLOOD-VESSELS ; SOLID TUMORS ; RGD ; MICROENVIRONMENT ; CELLS ; NANOMEDICINES
收录类别SCI
语种英语
项目资助者National Natural Science Foundation of China(81130059) ; National Basic Research Program of China (973 program)(2015CB932100)
WOS研究方向Chemistry ; Pharmacology & Pharmacy
WOS类目Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS记录号WOS:000384699900018
引用统计
文献类型期刊论文
条目标识符http://ir.ia.ac.cn/handle/173211/12639
专题中国科学院分子影像重点实验室
作者单位1.Peking Univ, Beijing Key Lab Mol Pharmaceut, Beijing 100191, Peoples R China
2.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
3.Chinese Acad Sci, Inst Automat, Key Lab Mol Imaging, Beijing 100190, Peoples R China
4.Peking Univ, Med & Hlth Analyt Ctr, Beijing 100191, Peoples R China
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Wang, Dan,Fu, Jijun,Shi, Yujie,et al. The modulation of tumor vessel permeability by thalidomide and its impacts on different types of targeted drug delivery systems in a sarcoma mouse model[J]. JOURNAL OF CONTROLLED RELEASE,2016,238:186-196.
APA Wang, Dan.,Fu, Jijun.,Shi, Yujie.,Peng, Dong.,Yuan, Lan.,...&Zhang, Qiang.(2016).The modulation of tumor vessel permeability by thalidomide and its impacts on different types of targeted drug delivery systems in a sarcoma mouse model.JOURNAL OF CONTROLLED RELEASE,238,186-196.
MLA Wang, Dan,et al."The modulation of tumor vessel permeability by thalidomide and its impacts on different types of targeted drug delivery systems in a sarcoma mouse model".JOURNAL OF CONTROLLED RELEASE 238(2016):186-196.
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