Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China.
Nanoscale. 2020 Feb 6;12(5):3090-3102. doi: 10.1039/c9nr07947e.
The critical issue in nanoscale medicine delivery systems is the targeted efficiency to guarantee the maximum accumulation of nanodrugs in tumors to exert better therapeutic action. In this study, we adopted an active and potent strategy based on mesenchymal stem cells (MSCs) certified with excellent tumor-tropism ability to load and ship MnO2@Ce6 nanoparticles into a tumor site. Notably, under the premise of the negligible cellular toxicity of MnO2@Ce6 on MSCs, its considerable uptake by MSCs enabled this nanoplatform (MnO2@Ce6-MSCs) to distribute increasingly inside the tumor. Briefly, a Ce6 photosensitizer was bound to MnO2 nanospheres by physical adsorption, improving its own stability in blood circulation. Furthermore, the delivered MnO2@Ce6 could modulate the tumor microenvironment (TME) by high sensitivity to excess hydrogen protons (H+) and H2O2. Thus, O2 generated by these reactions served as an abundant source for 1O2 conversion under a 633 nm laser exposure, which overcame the crucial bottleneck of the unfavorable hypoxia condition in TME for photodynamic therapy (PDT). In addition, MnO2 decomposed into Mn2+, which was represented by high T1 relaxivity in magnetic resonance imaging (MRI). The Mn2+ was finally removed rapidly from the body by liver metabolism and kidney filtration. These results endowed the original nanoplatform with striking potential for MSC-guided, Ce6-converted, MRI-monitored PDT for further innovation of a clinical cancer diagnosis-treatment agent.
纳米医学递药系统的关键问题是靶向效率，以保证纳米药物在肿瘤中的最大积累，从而发挥更好的治疗作用。在这项研究中，我们采用了一种基于间充质干细胞（MSCs）的主动高效策略，这些细胞被证明具有出色的肿瘤趋向能力，能够将 MnO2@Ce6 纳米颗粒装载并运送到肿瘤部位。值得注意的是，在 MnO2@Ce6 对 MSCs 具有可忽略的细胞毒性的前提下，其被 MSCs 的大量摄取使得这种纳米平台（MnO2@Ce6-MSCs）能够在肿瘤内分布得越来越多。简而言之，Ce6 光敏剂通过物理吸附结合到 MnO2 纳米球上，提高了其在血液循环中的稳定性。此外，递送到肿瘤部位的 MnO2@Ce6 可以通过对过量的氢质子（H+）和 H2O2 的高敏感性来调节肿瘤微环境（TME）。因此，这些反应产生的 O2 作为 633nm 激光照射下 1O2 转化的丰富来源，克服了 TME 中不利于光动力治疗（PDT）的缺氧条件的关键瓶颈。此外，MnO2 分解为 Mn2+，在磁共振成像（MRI）中表现出高 T1 弛豫率。最终，Mn2+ 通过肝脏代谢和肾脏过滤从体内迅速清除。这些结果使原始纳米平台具有 MSC 引导、Ce6 转化、MRI 监测 PDT 的显著潜力，为临床癌症诊断和治疗药物的进一步创新提供了可能。
