Multifunctional nanoparticles combining therapy and imaging have the potential to improve cancer treatment by allowing personalized therapy. Herein, we aimed to compare in vivo different strategies in terms of targeting capabilities: (1) passive targeting via the EPR effect, (2) active targeting of αvβ3 integrin via RGD grafting, (3) magnetic targeting via a magnet placed on the tumor and (4) the combination of magnetic targeting and active targeting of αvβ3 integrin. For a translational approach, PLGA-based nanoparticles loaded with paclitaxel and superparamagnetic iron oxides were used. Electron Spin Resonance spectroscopy and Magnetic Resonance Imaging (MRI) were used to both quantify and visualize the accumulation of multifunctional nanoparticles into the tumors. We demonstrate that compared to untargeted or single targeted nanoparticles, the combination of both active strategy and magnetic targeting drastically enhanced (i) nanoparticle accumulation into the tumor tissue with an 8-fold increase compared to passive targeting (1.12% and 0.135% of the injected dose, respectively), (ii) contrast in MRI (imaging purpose) and (iii) anti-cancer efficacy with a median survival time of 22 days compared to 13 for the passive targeting (therapeutic purpose). Double targeting of nanoparticles to tumors by different mechanisms could be a promising translational approach for the management of therapeutic treatment and personalized therapy.

译文

结合治疗和成像的多功能纳米颗粒有可能通过允许个性化治疗来改善癌症治疗。在此,我们旨在比较体内靶向能力方面的不同策略 :( 1) 通过EPR效应进行被动靶向,(2) 通过RGD移植对 αvβ3整联蛋白进行主动靶向,(3) 通过放置在肿瘤上的磁体进行磁靶向,以及 (4) 磁靶向和 αvβ3整合素的主动靶向的组合。对于翻译方法,使用了载有紫杉醇和超顺磁性氧化铁的基于PLGA的纳米颗粒。电子自旋共振波谱和磁共振成像 (MRI) 用于量化和可视化多功能纳米颗粒在肿瘤中的积累。我们证明,与非靶向或单一靶向纳米颗粒相比,主动策略和磁靶向的组合大大增强了 (i) 纳米颗粒积累到肿瘤组织中,与被动靶向相比增加了8倍 (分别为注射剂量的1.12% 和0.135%),(ii) MRI (成像目的) 和 (iii) 抗癌疗效的对比,中位生存时间为22天,而被动靶向 (治疗目的) 为13天。通过不同的机制将纳米颗粒双重靶向肿瘤可能是治疗治疗和个性化治疗管理的一种有前途的转化方法。

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