Transferrin-Bearing, Zein-Based Hybrid Lipid Nanoparticles for Drug and Gene Delivery to Prostate Cancer Cells

Gene therapy holds great promise for treating prostate cancer unresponsive to conventional therapies. However, the lack of delivery systems that can transport therapeutic DNA and drugs while targeting tumors without harming healthy tissues presents a significant challenge. This study aimed to explor...

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Main Authors: Khadeejah Maeyouf, Intouch Sakpakdeejaroen, Sukrut Somani, Jitkasem Meewan, Hawraa Ali-Jerman, Partha Laskar, Margaret Mullin, Graeme MacKenzie, Rothwelle J. Tate, Christine Dufès
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/15/11/2643
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author Khadeejah Maeyouf
Intouch Sakpakdeejaroen
Sukrut Somani
Jitkasem Meewan
Hawraa Ali-Jerman
Partha Laskar
Margaret Mullin
Graeme MacKenzie
Rothwelle J. Tate
Christine Dufès
author_facet Khadeejah Maeyouf
Intouch Sakpakdeejaroen
Sukrut Somani
Jitkasem Meewan
Hawraa Ali-Jerman
Partha Laskar
Margaret Mullin
Graeme MacKenzie
Rothwelle J. Tate
Christine Dufès
author_sort Khadeejah Maeyouf
collection DOAJ
description Gene therapy holds great promise for treating prostate cancer unresponsive to conventional therapies. However, the lack of delivery systems that can transport therapeutic DNA and drugs while targeting tumors without harming healthy tissues presents a significant challenge. This study aimed to explore the potential of novel hybrid lipid nanoparticles, composed of biocompatible zein and conjugated to the cancer-targeting ligand transferrin. These nanoparticles were designed to entrap the anti-cancer drug docetaxel and carry plasmid DNA, with the objective of improving the delivery of therapeutic payloads to prostate cancer cells, thereby enhancing their anti-proliferative efficacy and gene expression levels. These transferrin-bearing, zein-based hybrid lipid nanoparticles efficiently entrapped docetaxel, leading to increased uptake by PC-3 and LNCaP cancer cells and significantly enhancing anti-proliferative efficacy at docetaxel concentrations exceeding 1 µg/mL. Furthermore, they demonstrated proficient DNA condensation, exceeding 80% at polymer–DNA weight ratios of 1500:1 and 2000:1. This resulted in increased gene expression across all tested cell lines, with the highest transfection levels up to 11-fold higher than those observed with controls, in LNCaP cells. These novel transferrin-bearing, zein-based hybrid lipid nanoparticles therefore exhibit promising potential as drug and gene delivery systems for prostate cancer therapy.
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spelling doaj.art-f0f156a639e94ad69482ba726d7aba092023-11-24T15:01:14ZengMDPI AGPharmaceutics1999-49232023-11-011511264310.3390/pharmaceutics15112643Transferrin-Bearing, Zein-Based Hybrid Lipid Nanoparticles for Drug and Gene Delivery to Prostate Cancer CellsKhadeejah Maeyouf0Intouch Sakpakdeejaroen1Sukrut Somani2Jitkasem Meewan3Hawraa Ali-Jerman4Partha Laskar5Margaret Mullin6Graeme MacKenzie7Rothwelle J. Tate8Christine Dufès9Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UKStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UKStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UKStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UKStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UKStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UKGlasgow Imaging Facility, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UKStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UKStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UKStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UKGene therapy holds great promise for treating prostate cancer unresponsive to conventional therapies. However, the lack of delivery systems that can transport therapeutic DNA and drugs while targeting tumors without harming healthy tissues presents a significant challenge. This study aimed to explore the potential of novel hybrid lipid nanoparticles, composed of biocompatible zein and conjugated to the cancer-targeting ligand transferrin. These nanoparticles were designed to entrap the anti-cancer drug docetaxel and carry plasmid DNA, with the objective of improving the delivery of therapeutic payloads to prostate cancer cells, thereby enhancing their anti-proliferative efficacy and gene expression levels. These transferrin-bearing, zein-based hybrid lipid nanoparticles efficiently entrapped docetaxel, leading to increased uptake by PC-3 and LNCaP cancer cells and significantly enhancing anti-proliferative efficacy at docetaxel concentrations exceeding 1 µg/mL. Furthermore, they demonstrated proficient DNA condensation, exceeding 80% at polymer–DNA weight ratios of 1500:1 and 2000:1. This resulted in increased gene expression across all tested cell lines, with the highest transfection levels up to 11-fold higher than those observed with controls, in LNCaP cells. These novel transferrin-bearing, zein-based hybrid lipid nanoparticles therefore exhibit promising potential as drug and gene delivery systems for prostate cancer therapy.https://www.mdpi.com/1999-4923/15/11/2643zein-based hybrid lipid nanoparticlestransferrintumor targetingdelivery systemcancer therapyprostate cancer
spellingShingle Khadeejah Maeyouf
Intouch Sakpakdeejaroen
Sukrut Somani
Jitkasem Meewan
Hawraa Ali-Jerman
Partha Laskar
Margaret Mullin
Graeme MacKenzie
Rothwelle J. Tate
Christine Dufès
Transferrin-Bearing, Zein-Based Hybrid Lipid Nanoparticles for Drug and Gene Delivery to Prostate Cancer Cells
Pharmaceutics
zein-based hybrid lipid nanoparticles
transferrin
tumor targeting
delivery system
cancer therapy
prostate cancer
title Transferrin-Bearing, Zein-Based Hybrid Lipid Nanoparticles for Drug and Gene Delivery to Prostate Cancer Cells
title_full Transferrin-Bearing, Zein-Based Hybrid Lipid Nanoparticles for Drug and Gene Delivery to Prostate Cancer Cells
title_fullStr Transferrin-Bearing, Zein-Based Hybrid Lipid Nanoparticles for Drug and Gene Delivery to Prostate Cancer Cells
title_full_unstemmed Transferrin-Bearing, Zein-Based Hybrid Lipid Nanoparticles for Drug and Gene Delivery to Prostate Cancer Cells
title_short Transferrin-Bearing, Zein-Based Hybrid Lipid Nanoparticles for Drug and Gene Delivery to Prostate Cancer Cells
title_sort transferrin bearing zein based hybrid lipid nanoparticles for drug and gene delivery to prostate cancer cells
topic zein-based hybrid lipid nanoparticles
transferrin
tumor targeting
delivery system
cancer therapy
prostate cancer
url https://www.mdpi.com/1999-4923/15/11/2643
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