Soft Mesoporous Organosilica Nanoplatforms Improve Blood Circulation,Tumor Accumulation/Penetration,and Photodynamic Efficacy  

作　　者：Xin Peng Kun Chen Wanhua Liu Xiongfeng Cao Mengru Wang Jun Tao Ying Tian Lei Bao Guangming Lu Zhaogang Teng 

机构地区：[1]Jiangsu Key Laboratory of Molecular and Functional Imaging,Department of Radiology,Zhongda Hospital,School of Medicine,Southeast University,Nanjing 210009,Jiangsu,People’s Republic of China [2]Department of Medical Imaging,Jinling Hospital,School of Medicine,Nanjing University,Nanjing 210002,People’s Republic of China [3]Key Laboratory for Organic Electronics and Information Displays,Jiangsu Key Laboratory for Biosensors,Institute of Advanced Materials,Jiangsu National Synergetic Innovation Centre for Advanced Materials,Nanjing University of Posts and Telecommunications,Nanjing 210023,People’s Republic of China [4]Affiliated Hospital of Jiangsu University,Jiangsu University,Zhenjiang 212001,People’s Republic of China [5]Soft Matter and Interface Group,School of Engineering,RMIT University,Melbourne,VIC 3000,Australia

出　　处：《Nano-Micro Letters》2020年第10期205-223,共19页纳微快报（英文版）

基　　金：supported by National Key Basic Research Program of China(973 Program),China(2014CB744504);the National Natural Science Foundation of China,China(81971675,21603106 and 81971681);the Natural Science Foundation of Jiangsu Province,China(BK20160017)。

摘　　要：To date,the ability of nanoplatforms to achieve excellent therapeutic responses is hindered by short blood circulation and limited tumor accumulation/penetration.Herein,a soft mesoporous organosilica nanoplatform modified with hyaluronic acid and cyanine 5.5 are prepared,denoted SMONs-HA-Cy5.5,and comparative studies between SMONs-HA-Cy5.5(24.2 MPa)and stiff counterparts(79.2 MPa)are conducted.Results indicate that,apart from exhibiting a twofold increase in tumor cellular uptake,the soft nanoplatforms also display a remarkable pharmacokinetic advantage,resulting in considerably improved tumor accumulation.Moreover,SMONs-HA-Cy5.5 exhibits a significantly higher tumor penetration,achieving 30-μm deeper tissue permeability in multicellular spheroids relative to the stiff counterparts.Results further reveal that the soft nanoplatforms have an easier extravasation from the tumor vessels,diffuse farther in the dense extracellular matrix,and reach deeper tumor tissues compared to the stiff ones.Specifically,the soft nanoplatforms generate a 16-fold improvement(43 vs.2.72μm)in diffusion distance in tumor parenchyma.Based on the significantly improved blood circulation and tumor accumulation/penetration,a soft therapeutic nanoplatform is constructed by loading photosensitizer chlorin e6 in SMONs-HA-Cy5.5.The resulting nanoplatform exhibits considerably higher therapeutic efficacy on tumors compared to the stiff ones.

关 键 词：Mesoporous organosilica Soft nanoplatform Long circulation Tumor accumulation Tumor penetration 

分 类 号：R318.08[医药卫生—生物医学工程] TB383.1[医药卫生—基础医学]