Zhang Zhiming, Huang Chenlu, Zhang Li, Guo Qing, Qin Yu, Fan Fan, Li Boxuan, Xiao Bao, Zhu Dunwan, Zhang Linhua
Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China.
Acta Pharm Sin B. 2021 Feb;11(2):520-533. doi: 10.1016/j.apsb.2020.08.013. Epub 2020 Sep 2.
Chemotherapy has been a major option in clinic treatment of malignant tumors. However, single chemotherapy faces some drawbacks, such as multidrug resistance, severe side effects, which hinder its clinic application in tumor treatment. Multifunctional nanoparticles loading with chemotherapeutic agent and photosensitizer could be a promising way to efficiently conduct tumor combination therapy. In the current study, a novel pH-sensitive and bubble-generating mesoporous silica-based drug delivery system (denoted as M(a)D@PI-PEG-RGD) was constructed. Ammonium bicarbonate (NHHCO; abc) and chemotherapeutic agent doxorubicin (DOX) were loaded into the pores of mesoporous silica. Indocyanine green (ICG) as a photothermal and photodynamic agent was loaded onto the polydopamine (PDA) layer surface. The synthesized nanoparticles displayed a narrow polydispersity (PDI) and small particle size as characterized through dynamic light scattering-autosizer analysis. The nanoparticles also showed high targeting efficacy through RGD modification as indicated by cellular uptake and animal studies. DOX release analysis confirmed that the nanoparticles were pH-dependent and that NHHCO accelerated drug release. At the same time, the nanoparticles had obvious photothermal and photodynamic effects performed by ICG which restrained tumor growth remarkably. In summary, the multifunctional nanoparticles presented a promising system for combination therapy.
化疗一直是恶性肿瘤临床治疗的主要选择。然而，单一化疗存在一些缺点，如多药耐药性、严重的副作用，这阻碍了其在肿瘤治疗中的临床应用。负载化疗药物和光敏剂的多功能纳米粒子可能是有效进行肿瘤联合治疗的一种有前景的方法。在本研究中，构建了一种新型的基于介孔二氧化硅的pH敏感且能产生气泡的药物递送系统（记为M(a)D@PI-PEG-RGD）。将碳酸氢铵（NHHCO；abc）和化疗药物阿霉素（DOX）负载到介孔二氧化硅的孔中。将作为光热和光动力剂的吲哚菁绿（ICG）负载到聚多巴胺（PDA）层表面。通过动态光散射自动粒度分析仪分析表明，合成的纳米粒子具有窄的多分散性（PDI）和小粒径。细胞摄取和动物研究表明，纳米粒子通过RGD修饰还表现出高靶向效率。DOX释放分析证实纳米粒子具有pH依赖性，并且NHHCO加速了药物释放。同时，纳米粒子通过ICG表现出明显的光热和光动力效应，显著抑制了肿瘤生长。总之，多功能纳米粒子为联合治疗提供了一个有前景的系统。
