The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China; Department of Radiology, School of Medicine, Stanford University, Palo Alto, CA, 94304, United States.
The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
Biomaterials. 2021 Sep;276:121056. doi: 10.1016/j.biomaterials.2021.121056. Epub 2021 Jul 31.
Exosomes, endogenous nanosized particles (50-150 nm) secreted and absorbed by cells, have been recently used as diagnostic and therapeutic platforms in cancer treatment. The integration of exosome-based delivery with multiple therapeutic modalities could result in better clinical outcomes and reduced-sided effects. Here, we combined the targeting and biocompatibility of designer exosomes with chemo/gene/photothermal therapy. Our platform consists of exosomes loaded with internalized doxorubicin (DOX, a model cancer drug) and coated with magnetic nanoparticles conjugated with molecular beacons capable of targeting miR-21 for responsive molecular imaging. The coated magnetic nanoparticle enables enrichment of the exosomes at the tumor site by external magnetic field guidance. After the exosomes are gathered at the tumor site, the application of near-infrared radiation (NIR) induces localized hyperthermia and triggers the release of cargoes loaded inside the exosome. The released molecular beacon can target the miR-21 for both imaging and gene silencing. Meanwhile, the released doxorubicin serves to kill the cancer cells. About 91.04 % of cancer cells are killed after treatment with Exo-DOX-FeO@PDA-MB under NIR. The ability of the exosome-based method for cancer therapy has been demonstrated by animal models, in which the tumor size is reduced dramatically by 97.57 % with a magnetic field-guided tumor-targeted chemo/gene/photothermal approach. Thus, we expected this designer exosome-mediated multi-mode therapy to be a promising platform for the next-generation precision cancer nanomedicines.
外泌体是细胞分泌和吸收的内源性纳米颗粒（50-150nm），最近已被用作癌症治疗的诊断和治疗平台。将基于外泌体的递药与多种治疗方式相结合，可能会带来更好的临床效果和降低副作用。在这里，我们将设计型外泌体的靶向性和生物相容性与化疗/基因/光热治疗相结合。我们的平台由负载内化阿霉素（DOX，一种模型抗癌药物）的外泌体和涂有磁性纳米粒子组成，这些磁性纳米粒子与能够靶向 miR-21 的分子信标偶联，用于响应性分子成像。涂覆的磁性纳米粒子可通过外部磁场引导在外泌体在肿瘤部位富集。在外泌体聚集在肿瘤部位后，近红外辐射（NIR）的应用会引起局部过热，并触发内部装载的货物的释放。释放的分子信标可用于靶向 miR-21 进行成像和基因沉默。同时，释放的阿霉素可用于杀死癌细胞。在用 NIR 处理 Exo-DOX-FeO@PDA-MB 后，约 91.04%的癌细胞被杀死。动物模型已经证明了基于外泌体的癌症治疗方法的能力，其中通过磁场引导的肿瘤靶向化疗/基因/光热方法，肿瘤大小显著减少了 97.57%。因此，我们期望这种设计型外泌体介导的多模式治疗成为下一代精准癌症纳米药物的有前途的平台。
