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巨噬细胞在基于氧化铁纳米颗粒矢量化的抗肿瘤策略中的效用。

Utility of macrophages in an antitumor strategy based on the vectorization of iron oxide nanoparticles.

作者信息

Dalzon Bastien, Guidetti Mélanie, Testemale Denis, Reymond Solveig, Proux Olivier, Vollaire Julien, Collin-Faure Véronique, Testard Isabelle, Fenel Daphna, Schoehn Guy, Arnaud Josiane, Carrière Marie, Josserand Véronique, Rabilloud Thierry, Aude-Garcia Catherine

机构信息

Univ.Grenoble Alpes, CNRS, CEA, Laboratory of Chemistry and Biology of Metals, BIG-LCBM, 38000 Grenoble, France.

出版信息

Nanoscale. 2019 May 16;11(19):9341-9352. doi: 10.1039/c8nr03364a.

Abstract

Many solid tumors and their metastases are still resistant to current cancer treatments such as chemo- and radiotherapy. The presence of a small population of Cancer Stem Cells in tumors is held responsible for relapses. Moreover, the various physical barriers of the organism (e.g. blood-brain barrier) prevent many drugs from reaching the target cells. In order to alleviate this constraint, we suggest a Trojan horse strategy consisting of intravascular injection of macrophages loaded with therapeutic nanoparticles (an iron nanoparticle-based solution marketed under the name of FERINJECT®) to bring a high quantity of the latter to the tumor. The aim of this article is to assess the response of primary macrophages to FERINJECT® via functional assays in order to ensure that the macrophages loaded with these nanoparticles are still relevant for our strategy. Following this first step, we demonstrate that the loaded macrophages injected into the bloodstream are able to migrate to the tumor site using small-animal imaging. Finally, using synchrotron radiation, we validate an improvement of the radiotherapeutic effect when FERINJECT®-laden macrophages are deposited at the vicinity of cancer cells and irradiated.

摘要

许多实体瘤及其转移灶对当前的癌症治疗方法(如化疗和放疗)仍具有抗性。肿瘤中一小部分癌症干细胞的存在被认为是复发的原因。此外,机体的各种物理屏障(如血脑屏障)会阻止许多药物到达靶细胞。为了缓解这一限制,我们提出了一种特洛伊木马策略,即通过血管内注射负载治疗性纳米颗粒(一种名为FERINJECT®的基于铁纳米颗粒的溶液)的巨噬细胞,将大量纳米颗粒带到肿瘤部位。本文的目的是通过功能测定评估原代巨噬细胞对FERINJECT®的反应,以确保负载这些纳米颗粒的巨噬细胞对我们的策略仍然有效。在这第一步之后,我们证明注入血液中的负载巨噬细胞能够利用小动物成像迁移到肿瘤部位。最后,利用同步辐射,我们验证了当负载FERINJECT®的巨噬细胞沉积在癌细胞附近并接受照射时,放射治疗效果得到了改善。

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