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

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 is...

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Main Authors: Zanib Chaudhary, Sugarniya Subramaniam, Gul Majid Khan, Muhammad Mustafa Abeer, Zhi Qu, Taskeen Janjua, Tushar Kumeria, Jyotsna Batra, Amirali Popat
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-09-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fbioe.2019.00225/full
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author Zanib Chaudhary
Zanib Chaudhary
Sugarniya Subramaniam
Sugarniya Subramaniam
Sugarniya Subramaniam
Gul Majid Khan
Muhammad Mustafa Abeer
Zhi Qu
Taskeen Janjua
Tushar Kumeria
Tushar Kumeria
Tushar Kumeria
Jyotsna Batra
Jyotsna Batra
Jyotsna Batra
Amirali Popat
Amirali Popat
Amirali Popat
author_facet Zanib Chaudhary
Zanib Chaudhary
Sugarniya Subramaniam
Sugarniya Subramaniam
Sugarniya Subramaniam
Gul Majid Khan
Muhammad Mustafa Abeer
Zhi Qu
Taskeen Janjua
Tushar Kumeria
Tushar Kumeria
Tushar Kumeria
Jyotsna Batra
Jyotsna Batra
Jyotsna Batra
Amirali Popat
Amirali Popat
Amirali Popat
author_sort Zanib Chaudhary
collection DOAJ
description 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.
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spelling doaj.art-aeb4ff56e84a4081b335ac20b4a889512022-12-22T03:14:00ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852019-09-01710.3389/fbioe.2019.00225482266Encapsulation and Controlled Release of Resveratrol Within Functionalized Mesoporous Silica Nanoparticles for Prostate Cancer TherapyZanib Chaudhary0Zanib Chaudhary1Sugarniya Subramaniam2Sugarniya Subramaniam3Sugarniya Subramaniam4Gul Majid Khan5Muhammad Mustafa Abeer6Zhi Qu7Taskeen Janjua8Tushar Kumeria9Tushar Kumeria10Tushar Kumeria11Jyotsna Batra12Jyotsna Batra13Jyotsna Batra14Amirali Popat15Amirali Popat16Amirali Popat17School of Pharmacy, The University of Queensland, Brisbane, QLD, AustraliaDepartment of Pharmacy, Quaid-i-Azam University, Islamabad, PakistanSchool of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, AustraliaFaculty of Health, Institute of Health and Biomedical Innovation, Australian Prostate Cancer Research Centre-Queensland, Queensland University of Technology, Brisbane, QLD, AustraliaTranslational Research Institute, Woolloongabba, QLD, AustraliaDepartment of Pharmacy, Quaid-i-Azam University, Islamabad, PakistanSchool of Pharmacy, The University of Queensland, Brisbane, QLD, AustraliaSchool of Pharmacy, The University of Queensland, Brisbane, QLD, AustraliaSchool of Pharmacy, The University of Queensland, Brisbane, QLD, AustraliaSchool of Pharmacy, The University of Queensland, Brisbane, QLD, AustraliaTranslational Research Institute, Woolloongabba, QLD, AustraliaMater Research Institute, Woolloongabba, QLD, AustraliaSchool of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, AustraliaFaculty of Health, Institute of Health and Biomedical Innovation, Australian Prostate Cancer Research Centre-Queensland, Queensland University of Technology, Brisbane, QLD, AustraliaTranslational Research Institute, Woolloongabba, QLD, AustraliaSchool of Pharmacy, The University of Queensland, Brisbane, QLD, AustraliaTranslational Research Institute, Woolloongabba, QLD, AustraliaMater Research Institute, Woolloongabba, QLD, AustraliaResveratrol (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.https://www.frontiersin.org/article/10.3389/fbioe.2019.00225/fullresveratrolmesoporous silica nanoparticleschemotherapyanti-cancer activityprostate cancer
spellingShingle Zanib Chaudhary
Zanib Chaudhary
Sugarniya Subramaniam
Sugarniya Subramaniam
Sugarniya Subramaniam
Gul Majid Khan
Muhammad Mustafa Abeer
Zhi Qu
Taskeen Janjua
Tushar Kumeria
Tushar Kumeria
Tushar Kumeria
Jyotsna Batra
Jyotsna Batra
Jyotsna Batra
Amirali Popat
Amirali Popat
Amirali Popat
Encapsulation and Controlled Release of Resveratrol Within Functionalized Mesoporous Silica Nanoparticles for Prostate Cancer Therapy
Frontiers in Bioengineering and Biotechnology
resveratrol
mesoporous silica nanoparticles
chemotherapy
anti-cancer activity
prostate cancer
title Encapsulation and Controlled Release of Resveratrol Within Functionalized Mesoporous Silica Nanoparticles for Prostate Cancer Therapy
title_full Encapsulation and Controlled Release of Resveratrol Within Functionalized Mesoporous Silica Nanoparticles for Prostate Cancer Therapy
title_fullStr Encapsulation and Controlled Release of Resveratrol Within Functionalized Mesoporous Silica Nanoparticles for Prostate Cancer Therapy
title_full_unstemmed Encapsulation and Controlled Release of Resveratrol Within Functionalized Mesoporous Silica Nanoparticles for Prostate Cancer Therapy
title_short Encapsulation and Controlled Release of Resveratrol Within Functionalized Mesoporous Silica Nanoparticles for Prostate Cancer Therapy
title_sort encapsulation and controlled release of resveratrol within functionalized mesoporous silica nanoparticles for prostate cancer therapy
topic resveratrol
mesoporous silica nanoparticles
chemotherapy
anti-cancer activity
prostate cancer
url https://www.frontiersin.org/article/10.3389/fbioe.2019.00225/full
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