Photosensitizer-Encapsulated Ferritins Mediate Photodynamic Therapy against Cancer-Associated Fibroblasts and Improve Tumor Accumulation of Nanoparticles.
Photosensitizer-Encapsulated Ferritins Mediate Photodynamic Therapy against Cancer-Associated Fibroblasts and Improve Tumor Accumulation of Nanoparticles.
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光敏剂封装的铁蛋白介导针对癌症相关成纤维细胞的光动力疗法并改善纳米颗粒的肿瘤积累
DOI：
10.1021/acs.molpharmaceut.8b00419
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发表时间：
2018-08-06
影响因子：
4.9
通讯作者：
Ma Q
中科院分区：
文献类型：
--
作者：
Li L;Zhou S;Lv N;Zhen Z;Liu T;Gao S;Xie J;Ma Q
纳米颗粒作为药物递送载体或显像剂已被广泛测试，主要是由于它们通过增强渗透性和滞留性（EPR）效应在肿瘤中选择性积累的能力。然而，研究表明，许多肿瘤的EPR效果较差，许多纳米颗粒外渗后被困在血管周围区域，几乎不能迁移到肿瘤中心。这在很大程度上归因于致密的肿瘤细胞外基质（ECM），它作为物理屏障阻止纳米颗粒的有效外渗和扩散。在这项研究中，我们报告了一种光动力治疗（PDT）方法来增强纳米颗粒的肿瘤摄取。简单地说，我们将光敏剂ZnF16Pc包封到铁蛋白纳米笼中，然后将成纤维细胞活化蛋白（FAP）特异性的单链活片段（scFv）序列偶联到铁蛋白表面。FAP是一种在癌症相关成纤维细胞（CAF）中广泛上调的血浆表面蛋白，CAF是ECM纤维成分的主要来源。我们发现scFv结合和ZnF16Pc负载的铁蛋白纳米颗粒（scFv-Z@FRT）可以介导高效和选择性的PDT，导致肿瘤中CAFs的根除。在双侧4T1肿瘤模型中，我们发现scFv-Z@FRT介导PDT后，血清白蛋白（BSA）、10 nm量子点（QDs）和50 nm量子点的肿瘤蓄积分别增加了2倍、3.5倍和18倍。我们的研究提出了一种新的、安全的方法来增强纳米颗粒对肿瘤的递送。
Nanoparticles have been widely tested as drug delivery carriers or imaging agents, largely due to their ability to selectively accumulate in tumors through the enhanced permeability and retention (EPR) effect. However, studies show that many tumors afford less efficient EPR effect and that many nanoparticles are trapped in the peri-vascular region after extravasation and barely migrate into tumor centers. This is to a large degree attributed to the dense tumor extracellular matrix (ECM), which functions as a physical barrier to prevent efficient nanoparticle extravasation and diffusion. In this study, we report a photodynamic therapy (PDT) approach to enhance tumor uptake of nanoparticles. Briefly, we encapsulate ZnF16Pc, a photosensitizer, into ferritin nanocages, and then conjugate to the surface of the ferritin a single chain viable fragment (scFv) sequence specific to fibroblast activation protein (FAP). FAP is a plasma surface protein widely upregulated in cancer-associated fibroblast (CAF), which is a major source of the ECM fiber components. We found that the scFv conjugated and ZnF16Pc loaded ferritin nanoparticles (scFv-Z@FRT) can mediate efficient and selective PDT, leading to eradication of CAFs in tumors. When tested in bilateral 4T1 tumor models, we found that the tumor accumulation of serum albumin (BSA), 10 nm quantum dots (QDs), and 50 nm QDs, was increased by 2, 3.5, and 18 folds, after scFv-Z@FRT mediated PDT. Our studies suggest a novel and safe method to enhance the delivery of nanoparticles to tumors.
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影响因子：
8
作者：
Busch, S.;Acar, A.;Landberg, G.
通讯作者：
Landberg, G.
影响因子：
10.8
作者：
Lin X;Xie J;Niu G;Zhang F;Gao H;Yang M;Quan Q;Aronova MA;Zhang G;Lee S;Leapman R;Chen X
通讯作者：
Chen X
影响因子：
78.8
作者：
Jain, Rakesh K.;Stylianopoulos, Triantafyllos
通讯作者：
Stylianopoulos, Triantafyllos
DOI：
10.1002/adma.201604789
发表时间：
2017-07
期刊：
Advanced materials (Deerfield Beach, Fla.)
影响因子：
--
作者：
Huang L;Li Z;Zhao Y;Yang J;Yang Y;Pendharkar AI;Zhang Y;Kelmar S;Chen L;Wu W;Zhao J;Han G
通讯作者：
Han G
影响因子：
17.1
作者：
Zhen Z;Tang W;Guo C;Chen H;Lin X;Liu G;Fei B;Chen X;Xu B;Xie J
通讯作者：
Xie J