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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
Source PublicationJOURNAL OF CONTROLLED RELEASE
2016-09-28
Volume238Pages:186-196
SubtypeArticle
AbstractThe 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.
KeywordTargeted Drug Delivery Systems Animal Model Of Epr Effect Tumor Vessel Permeability Thalidomide Antitumor Efficacy Distribution
WOS HeadingsScience & Technology ; Physical Sciences ; Life Sciences & Biomedicine
DOI10.1016/j.jconrel.2016.07.014
WOS KeywordMACROMOLECULAR THERAPEUTICS ; TRANSFERRIN RECEPTOR ; VASCULAR-PERMEABILITY ; CANCER-CHEMOTHERAPY ; BLOOD-VESSELS ; SOLID TUMORS ; RGD ; MICROENVIRONMENT ; CELLS ; NANOMEDICINES
Indexed BySCI
Language英语
Funding OrganizationNational Natural Science Foundation of China(81130059) ; National Basic Research Program of China (973 program)(2015CB932100)
WOS Research AreaChemistry ; Pharmacology & Pharmacy
WOS SubjectChemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS IDWOS:000384699900018
Citation statistics
Cited Times:6[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ia.ac.cn/handle/173211/12639
Collection中国科学院分子影像重点实验室
Affiliation1.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
Recommended Citation
GB/T 7714
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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