Vascular-confined multi-passage discoidal nanoconstructs for the low-dose docetaxel inhibition of triple-negative breast cancer growth
作者机构：Laboratory of Nanotechnology for Precision MedicineFondazione Istituto Italiano di TecnologiaGenoa 16163Italy Department of InformaticsBioengineeringRobotics and System EngineeringUniversity of GenoaGenoa 16126Italy Nanochemistry LaboratoryFondazione Istituto Italiano di TecnologiaGenoa 16163Italy Analytical Chemistry LaboratoryFondazione Istituto Italiano di TecnologiaGenoa 16163Italy
出 版 物：《Nano Research》 (纳米研究（英文版）)
年 卷 期：2022年第15卷第1期
页 面：482-491页
核心收录：
学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 0808[工学-电气工程] 1002[医学-临床医学] 0809[工学-电子科学与技术（可授工学、理学学位）] 08[工学] 0805[工学-材料科学与工程（可授工学、理学学位）] 100214[医学-肿瘤学] 0836[工学-生物工程] 0702[理学-物理学] 10[医学]
基 金：supported by the European Research Council under the European Unions Seventh Framework Programme(FP7/2007-2013)/ERC grant agreement No.616695 by the Italian Association for Cancer Research(AIRC)under the individual investigator grant No.17664 and by the European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No.754490
主 题：hydrogel particles template strategy vascular targeting biomimicry cancer therapy
摘 要：Taxane efficacy in triple negative breast cancer(TNBC)is limited by insufficient tumor accumulation and severe off-target *** offer a unique opportunity to enhance the anti-cancer potency of this ***,1,000 nm×400 nm discoidal polymeric nanoconstructs(DPN)encapsulating docetaxel(DTXL)and the near infrared compound Iipid-Cy5 were *** were obtained by filling multiple times cylindrical wells in a poly(vinyl alcohol)template with a polymer mixture comprising poly(lactic-co-glycolic acid)(PLGA)and poly(ethylene glycol)diacrylate(PEG-DA)chains together with therapeutic and imaging *** resulting“multi-passageDPN exhibited higher DTXL loading,Iipid-Cy5 stability,and stiffness as compared to the conventionalsingle-passage*** microscopy confirmed that DTXL-DPN were not taken up by MDA-MB-231 cells but would rather sit next to the cell membrane and slowly release DTXL *** DPN had no toxicity on TNBC cells,whereas DTXL-DPN presented a cytotoxic potential comparable to free DTXL(IC_(50)=2.6 nM±1.0 nM vs.7.0 nM±1.09 nM at 72 h).In orthotopic murine models,DPN accumulated in TNBC more efficiently than *** only 2 mg/kg DTXL,intravenously administered every 2 days for a total of 13 treatments,DTXL-DPN induced tumor regression and were associated to an overall 80%survival rate as opposed to a 30%survival rate for free-DTXL,at 120 *** untreated mice succumbed before 90 ***,this data demonstrates that vascular confined multi-passage DPN,biomimicking the behavior of circulating platelets,can efficiently deliver chemotherapeutic molecules to malignant tissues and effectively treat orthotopic TNBC at minimal taxane doses.
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