School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, P. R. China.
Anal Chem. 2024 Aug 20;96(33):13557-13565. doi: 10.1021/acs.analchem.4c02244. Epub 2024 Aug 8.
Although targeted therapy has revolutionized oncotherapy, engineering a versatile oncotherapy nanoplatform integrating both diagnostics and therapeutics has always been an intractable challenge to overcome the limitations of monotherapy. Herein, a theranostics platform based on DI/MP-MB has successfully realized the fluorescence detection of disease marker miR-21 and the gene/photothermal/chemo triple synergetic cancer therapy, which can trace the tumor through photothermal and fluorescence dual-mode imaging and overcome the limitations of monotherapy to improve the treatment efficiency of tumors. DI/MP-MB was prepared by magnetic mesoporous silicon nanoparticles (M-MSNs) loaded with doxorubicin (Dox) and new indocyanine green (IR820), and subsequently coating polydopamine as a "gatekeeper", followed by the surface adsorbed with molecular beacons capable of targeting miR-21 for responsive imaging. Under the action of enhanced permeability retention and external magnetic field, DI/MP-MB were targeted and selectively accumulated in the tumor. MiR-21 MB hybridized with miR-21 to form a double strand, which led to the desorption of miR-21 MB from the polydopamine surface and the fluorescence recovery to realize gene silencing and fluorescence imaging for tracking the treatment process. Meanwhile, with the response to the near-infrared irradiation and the tumor's microacid environment, the outer layer polydopamine will decompose, releasing Dox and IR820 to realize chemotherapy and photothermal therapy. Finally, the ability of DI/MP-MB to efficiently suppress tumor growth was comprehensively assessed and validated both in vitro and in vivo. Noteworthily, the excellent anticancer efficiency by the synergistic effect of gene/photothermal/chemo triple therapy of DI/MP-MB makes it an ideal nanoplatform for tumor therapy and imaging.
虽然靶向治疗已经彻底改变了肿瘤治疗学,但工程化一种多功能的肿瘤治疗纳米平台,将诊断和治疗结合起来,一直是克服单药治疗局限性的一个难以克服的挑战。在这里,基于 DI/MP-MB 的治疗学平台成功地实现了疾病标志物 miR-21 的荧光检测和基因/光热/化疗三重协同癌症治疗,它可以通过光热和荧光双模成像来跟踪肿瘤,并克服单药治疗的局限性,提高肿瘤的治疗效率。DI/MP-MB 是通过载有多柔比星 (Dox) 和新型吲哚菁绿 (IR820) 的磁性介孔硅纳米粒子 (M-MSNs) 制备的,并随后用聚多巴胺作为“守门员”进行包覆,然后表面吸附能够靶向 miR-21 的分子信标,用于响应成像。在增强通透性保留和外部磁场的作用下,DI/MP-MB 被靶向并选择性地在肿瘤中积累。miR-21 MB 与 miR-21 杂交形成双链,导致 miR-21 MB 从聚多巴胺表面解吸,荧光恢复,从而实现基因沉默和荧光成像,以跟踪治疗过程。同时,随着近红外辐射和肿瘤微酸环境的响应,外层聚多巴胺会分解,释放 Dox 和 IR820 以实现化学治疗和光热治疗。最后,在体外和体内对 DI/MP-MB 高效抑制肿瘤生长的能力进行了全面评估和验证。值得注意的是,DI/MP-MB 的基因/光热/化疗三重协同治疗的优异抗癌效率使其成为肿瘤治疗和成像的理想纳米平台。