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Photosensitizer-Encapsulated Ferritins Mediate Photodynamic Therapy against Cancer-Associated Fibroblasts and Improve Tumor Accumulation of Nanoparticles
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2018-07-02 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b00419
Lu Li 1 , Shiyi Zhou , NingNing Lv 1 , Zipeng Zhen , Tianji Liu 1 , Shi Gao 1 , Jin Xie , Qingjie Ma 1
Affiliation  

Nanoparticles have been widely tested as drug delivery carriers or imaging agents, largely because of their ability to selectively accumulate in tumors through the enhanced permeability and retention (EPR) effect. However, studies show that many tumors afford a less efficient EPR effect and that many nanoparticles are trapped in the perivascular 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 fibroblasts (CAFs), which is a major source of the ECM fiber components. We found that the scFv-conjugated and ZnF16Pc-loaded ferritin nanoparticles ([email protected]) 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-fold after [email protected] mediated PDT. Our studies suggest a novel and safe method to enhance the delivery of nanoparticles to tumors.

中文翻译:

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

纳米颗粒已被广泛测试作为药物输送载体或显像剂,很大程度上是因为它们能够通过增强渗透性和保留(EPR)效应选择性地在肿瘤中积累。然而,研究表明,许多肿瘤的 EPR 效应效率较低,并且许多纳米颗粒在外渗后被困在血管周围区域,几乎无法迁移到肿瘤中心。这在很大程度上归因于致密的肿瘤细胞外基质(ECM),它充当物理屏障,防止纳米颗粒有效外渗和扩散。在这项研究中,我们报告了一种光动力疗法(PDT)方法来增强肿瘤对纳米颗粒的摄取。简而言之,我们将光敏剂 ZnF 16 Pc封装到铁蛋白纳米笼中,然后将成纤维细胞激活蛋白 (FAP) 特异性的单链活性片段 (scFv) 序列缀合到铁蛋白表面。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 缀合和 ZnF 16 Pc 负载的铁蛋白纳米颗粒([email protected])可以介导有效且选择性的 PDT,从而根除肿瘤中的 CAF。在双侧 4T1 肿瘤模型中进行测试时,我们发现血清白蛋白 (BSA)、10 nm 量子点 (QD) 和 50 nm QD 的肿瘤积累在 [email protected] 后增加了 2 倍、3.5 倍和 18 倍。 ] 介导的PDT。我们的研究提出了一种新颖且安全的方法来增强纳米粒子向肿瘤的递送。
更新日期:2018-07-02
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