pH-sensitive and bubble-generating mesoporous silica-based nanoparticles for enhanced tumor combination therapy

• Published in: Acta pharmaceutica Sinica. B 2021-02, Vol.11 (2), p.520-533
• Main Authors: Zhang, Zhiming, Huang, Chenlu, Zhang, Li, Guo, Qing, Qin, Yu, Fan, Fan, Li, Boxuan, Xiao, Bao, Zhu, Dunwan, Zhang, Linhua
• Format: Article
• Language: English
• Subjects: Bubble-generating; Combination therapy; Mesoporous silica; Original; pH-sensitive; Targeting modification
• ISSN: 2211-3835; 2211-3843
• DOI: 10.1016/j.apsb.2020.08.013

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 (NH4HCO3; 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 NH4HCO3 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. [Display omitted]