The use of hollow mesoporous silica nanospheres to encapsulate bortezomib and improve efficacy for non-small cell lung cancer therapy
Jia Shen
a, b, c, 1, Guosheng Song
d, 1, Man An
a, c, Xianqian Li
e, Ning Wu
e, Kangcheng Ruan
a, c, Junqing Hu
d, Ronggui Hu
a, c, a State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China
b University of Chinese Academy of Sciences, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China
c Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China
d State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China
e Department of Clinical Oncology, Xuhui Central Hospital, 966 Middle Huaihai Road, Shanghai 200031, China
Abstract
Bortezomib (BTZ) is the first clinically approved proteasome inhibitor for treating multiple human malignancies. However, the poor water-solubility and low stability of BTZ and the emergence of tumor resistance have severely restrained its therapeutic efficacy. Herein, we report the application of hollow mesoporous silica nanospheres (HMSNs) in encapsulating BTZ for drug delivery. In in vitro cell viability assay on human NSCLC H1299 cells, the half-maximum inhibiting concentration (IC50) of HMSNs–BTZ was 42% of that for free BTZ in 48 h treatments. In vivo tumor-suppression assay further indicated that HMSNs–BTZ (0.3 mg/kg) showed approximately 1.5 folds stronger anti-tumor activity than free BTZ. Furthermore, we report that more potent induction of cell cycle arrest and apoptotic cell death, along with promoted activation of Caspase 3 and autophagy might mechanistically underlie the improved anti-tumor efficacy of HMSNs–BTZ. Finally, the tumor-suppressing effect of HMSNs–BTZ was enhanced in the presence of wild-type p53 signaling, suggesting a potential enhancement in clinical efficacy with combined p53 gene therapy and BTZ-based chemotherapy. Therefore, the HMSNs-based nanoparticles are emerging as a promising platform to deliver therapeutic agents for beneficial clinical outcomes through lowering doses and frequency of drug administration and reducing potential side effects.
Keywords
Anti-tumor activity; Apoptotic cell death; Bortezomib; Drug delivery; Mesoporous silica; NSCLC
