Shanghai Key Laboratory of Female Reproductive Endocrine Related Disease, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People's Republic of China.
Department of Gynaecology and Obstetrics, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
Int J Nanomedicine. 2019 Sep 18;14:7665-7679. doi: 10.2147/IJN.S214377. eCollection 2019.
Drug resistance is one of the prime reasons of chemotherapy failure in breast cancer and is also an important factor affecting prognosis.
In this study, we constructed a functional magnetic mesoporous silica-based nanocomposite (MMSN) for breast cancer chemotherapy/photodynamic therapy.
MMSN was characterized by scanning electron microscopy and transmission electron microscopy to observe the morphology. The size distribution and zeta potential of the MSNs were determined using Malvern Particle Size Analyzer. Anti-tumor activity in vitro was investigated by CCK-8 assay, flow cytometry and transwell experiment, and the anti-tumor activity in vivo was probed into by magnetic targeting, toxicity, and antitumor effects in breast cancer-bearing BABL/c nude mice.
The results showed that the release of doxorubicin in the nanocomposites was pH sensitive, and the cumulative release rate reached 80.53% at 60 h under acidic conditions. The nanocomposites had a high cellular uptake ability in MCF-7/ADR cells, and the IC value of the nanocomposites on MCF-7/ADR cells was 4.23 μg/mL, much smaller than that of free DOX (363.2 μg/mL). The nanocomposites could effectively reverse resistance and induce apoptosis of MCF-7/ADR cells. The blood biochemistry parameters and H&E staining results showed no serious adverse effects after treatment with the nanocomposites. Prussian blue staining showed that the nanocomposites were able to target tumor tissues in tumor-bearing mice under a magnetic field. The combined chemical/photodynamic therapy significantly inhibited tumor growth in vivo.
Nanocomposites with magnetic and pH dual-responsive performance has shown a promising platform for enhanced drug-resistant breast cancer treatment.
耐药性是乳腺癌化疗失败的主要原因之一，也是影响预后的重要因素。
本研究构建了一种基于功能磁性介孔硅的纳米复合材料（MMSN），用于乳腺癌的化疗/光动力治疗。
通过扫描电子显微镜和透射电子显微镜观察形貌对 MMSN 进行了表征。使用 Malvern 粒度分析仪测定 MSNs 的粒径分布和 Zeta 电位。通过 CCK-8 测定、流式细胞术和 Transwell 实验研究了体外抗肿瘤活性，并通过磁靶向、毒性和荷乳腺癌 BABL/c 裸鼠的抗肿瘤作用研究了体内抗肿瘤活性。
结果表明，纳米复合材料中的阿霉素释放具有 pH 敏感性，在酸性条件下 60 h 时累积释放率达到 80.53%。纳米复合材料在 MCF-7/ADR 细胞中具有较高的细胞摄取能力，纳米复合材料对 MCF-7/ADR 细胞的 IC 值为 4.23 μg/mL，远小于游离 DOX（363.2 μg/mL）。纳米复合材料能有效逆转 MCF-7/ADR 细胞的耐药性并诱导其凋亡。血液生化参数和 H&E 染色结果表明，用纳米复合材料处理后无严重不良反应。普鲁士蓝染色表明，纳米复合材料在磁场下能够靶向荷瘤小鼠的肿瘤组织。联合化学/光动力治疗显著抑制了体内肿瘤的生长。
具有磁响应和 pH 双重响应性能的纳米复合材料为增强耐药性乳腺癌的治疗提供了一个有前途的平台。
