Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, P. R. China.
Biomater Sci. 2017 May 2;5(5):1001-1013. doi: 10.1039/c7bm00043j.
Multifunctional theranostics have offered some interesting new opportunities for cancer therapy and diagnosis in the last decade. Herein, magnetic mesoporous silica nanoparticles (M-MSNs) were designed and synthesized, then the photosensitizer chlorin e6 (Ce6) and antitumor drug doxorubicin (Dox) were adsorbed onto the M-MSNs. Biocompatible alginate/chitosan polyelectrolyte multilayers (PEM) were assembled on the M-MSNs to achieve a pH-responsive drug delivery system and adsorb P-gp shRNA for reversing the multidrug resistance. The obtained M-MSN(Dox/Ce6)/PEM/P-gp shRNA nanocomposites were characterized using TEM, SEM, X-ray diffraction, BET, FTIR and electrophoresis. The nanocomposites with average diameter of 280 nm exhibited a pH-responsive drug release profile, and more singlet oxygen generation in cancer cells after laser illumination. CCK-8 assay and calcein-AM/PI co-staining showed that the multifunctional nanocomplexes significantly increased cell apoptosis in vitro. With tumor-bearing Balb/c mice employed as the animal model, combined photodynamic therapy and chemotherapy was carried out, also achieving synergistic anti-tumor effects in vivo. The cores of bifunctional FeO-Au nanoparticles in the multifunctional nanocomposites enabled dual-modal MR and CT imaging, which illustrated strong tumor uptake of these nanocomposites after intravenous injection into tumor-bearing mice. This work highlights the great potential of magnetic mesoporous silica nanocomposites as a multifunctional delivery platform, which is promising for imaging-guided cancer combination therapy with high efficacy.
在过去的十年中，多功能治疗学为癌症治疗和诊断提供了一些有趣的新机会。在此，设计并合成了磁性介孔硅纳米粒子（M-MSNs），然后将光敏剂氯代叶绿素 e6（Ce6）和抗肿瘤药物阿霉素（Dox）吸附到 M-MSNs 上。将生物相容性的海藻酸钠/壳聚糖聚电解质多层（PEM）组装到 M-MSNs 上，以实现 pH 响应型药物递送系统，并吸附 P-gp shRNA 以逆转多药耐药性。使用 TEM、SEM、X 射线衍射、BET、FTIR 和电泳对获得的 M-MSN（Dox/Ce6）/PEM/P-gp shRNA 纳米复合材料进行了表征。平均直径为 280nm 的纳米复合材料表现出 pH 响应性药物释放特性，并且在激光照射后癌细胞中产生更多的单线态氧。CCK-8 测定和 calcein-AM/PI 共染色表明，多功能纳米复合物在体外显著增加了细胞凋亡。以荷瘤 Balb/c 小鼠为动物模型，进行光动力治疗和化疗联合治疗，在体内也达到了协同抗肿瘤作用。多功能纳米复合物中双功能 FeO-Au 纳米粒子的核心能够进行双模磁共振和 CT 成像，这表明这些纳米复合物在静脉注射到荷瘤小鼠后具有很强的肿瘤摄取能力。这项工作突出了磁性介孔硅纳米复合材料作为多功能递药平台的巨大潜力，有望用于高效的成像引导癌症联合治疗。
