文献类型：期刊文献

英文题名：Vasodilator Hydralazine Promotes Nanoparticle Penetration in Advanced Desmoplastic Tumors

作者：Chen, Yanzuo[1,2,3];Song, Wantong[1,2,4];Shen, Limei[1,2];Qiu, Nasha[1,2,5];Hu, Mengying[1,2];Liu, Yun[1,2];Liu, Qi[1,2];Huang, Leaf[1,2]

机构：[1]Univ N Carolina, Div Pharmacoengn & Mol Pharmaceut, Chapel Hill, NC 27599 USA;[2]Univ N Carolina, Eshelman Sch Pharm, Ctr Nanotechnol Drug Delivery, Chapel Hill, NC 27599 USA;[3]East China Univ Sci & Technol, Sch Pharm, Dept Pharmaceut, Shanghai 200237, Peoples R China;[4]Chinese Acad Sci, Changchun Inst Appl Chem, Key Lab Polymer Ecomat, Changchun 130022, Jilin, Peoples R China;[5]Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmaceut, Hangzhou 310058, Zhejiang, Peoples R China

年份：2019

卷号：13

期号：2

起止页码：1751

外文期刊名：ACS NANO

收录：;EI(收录号：20190406419508);WOS:【SCI-EXPANDED(收录号:WOS:000460199400075)】；

基金：This work was supported by NIH Grant No. CA198999, a grant from Eshelman Institute for Innovation, as well as a grant from China Scholarship Council (201706745002). We appreciate Dr. K.H. Lee and his group, especially Yungyi Cheng, for the assistance in the use of HPLC. Sara Musetti helped with text editing.

语种：英文

外文关键词：hydralazine; nanoparticles; tumor penetration; desmoplastic tumor; tumor microenvironment

摘要：Desmoplastic tumors are normally resistant to nanoparticle-based chemotherapy due to dense stroma and limited particle permeability inside the tumor. Herein, we reported that hydralazine (HDZ)-an antihypertension vasodilator-would dramatically promote nanoparticle penetration in advanced desmoplastic tumors. First, a HDZ-liposome system was developed for tumor-selective delivery of HDZ. After three injections of HDZ-liposomes at a dose of 15 mg/kg, the tumor stroma was remarkably reduced, along with ameliorated tumor hypoxia in murine models of desmoplastic melanoma (BPD6). Furthermore, HDZ-liposome treatment altered the immunosuppressive tumor microenvironment, which provided opportunities for applying this therapeutic system to aid immunotherapy in desmoplastic tumors. Using DiD-loaded liposome as a model nanoparticle, we showed that HDZ-liposome treatment significantly increased nanoparticle accumulation and penetration inside desmoplastic tumors. As a result, one single injection of doxorubicin-liposomes at a dose of 5 mg/kg resulted in strong tumor inhibition effect after HDZ-liposome pretreatment in the advanced desmoplastic melanoma with sizes over 400 mm(3). Because HDZ is a widely used antihypertension drug, the findings here should be readily translatable for clinical benefits.