Encapsulation and Controlled Release of Resveratrol Within Functionalized Mesoporous Silica Nanoparticles for Prostate Cancer Therapy

Frontiers in Bioengineering and Biotechnology

Gul Majid Khan¹  Zanib Chaudhary¹  Tushar Kumeria³  Amirali Popat³  Zhi Qu⁵  Muhammad Mustafa Abeer⁵  Taskeen Janjua⁵  Sugarniya Subramaniam⁶  Jyotsna Batra⁶ 

[1] Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan;Faculty of Health, Institute of Health and Biomedical Innovation, Australian Prostate Cancer Research Centre-Queensland, Queensland University of Technology, Brisbane, QLD, Australia;Mater Research Institute, Woolloongabba, QLD, Australia;School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia;School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia;Translational Research Institute, Woolloongabba, QLD, Australia;

关键词: resveratrol;    mesoporous silica nanoparticles;    chemotherapy;    anti-cancer activity;    prostate cancer;   

DOI  :  10.3389/fbioe.2019.00225

来源: DOAJ

【 摘 要 】

Resveratrol (RES) is a naturally existing polyphenol which exhibits anti-oxidant, anti-inflammatory, and anti-cancer properties. In recent years, RES has attracted attention for its synergistic effect with other anti-cancer drugs for the treatment of drug resistant cancers. However, RES faces the issues of poor pharmacokinetics, stability and low solubility which limits its clinical application. In present study, RES has been loaded onto uniformly sized (~60 nm) mesoporous silica nanoparticles (MSNs) to improve its in vitro anti-proliferative activity and sensitization of Docatexal in hypoxia induced drug resistance in prostate cancer. RES was efficiently encapsulated within phosphonate (negatively charged) and amine (positively charged) modified MSNs. The effect of surface functionalization was studied on the loading, in vitro release, anti-proliferative and cytotoxic potential of RES using prostate cancer cell line. At pH 7.4 both free and NH2-MSNs loaded RES showed burst release which was plateaued with almost 90% of drug released in first 12 h. On the other hand, PO3-MSNs showed significantly slower release kinetics with only 50% drug release in first 12 h at pH 7.4. At pH 5.5, however, both the PO3-MSNs and NH2-MSNs showed significant control over release (around 40% less release compared with free RES in 24 h). Phosphonate modified MSNs significantly enhanced the anti-proliferative potential of RES with an IC50 of 7.15 μM as compared to 14.86 μM of free RES whereas amine modified MSNs didn't affect proliferation with an IC50 value higher than free RES (20.45 μM). Furthermore, RES loaded onto PO3-MSNs showed robust and dose dependent sensitization of Docatexal in hypoxic cell environment which was comparable to pure RES solution. This study provides an example of applicability of MSNs loaded with polyphenols such as RES as next generation anticancer formulations for treating drug resistant cancers such as prostate cancer.

【 授权许可】

Unknown