Details
| Original language | English |
|---|---|
| Article number | 394 |
| Journal | Pharmaceutics |
| Volume | 13 |
| Issue number | 3 |
| Early online date | 16 Mar 2021 |
| Publication status | Published - Mar 2021 |
Abstract
Even though the administration of chemotherapeutic agents such as erlotinib is clinically established for the treatment of breast cancer, its efficiency and the therapy outcome can be greatly improved using RNA interference (RNAi) mechanisms for a combinational therapy. However, the cellular uptake of bare small interfering RNA (siRNA) is insufficient and its fast degradation in the bloodstream leads to a lacking delivery and no suitable accumulation of siRNA inside the target tissues. To address these problems, non-ionic surfactant vesicles (niosomes) were used as a nanocarrier platform to encapsulate Lifeguard (LFG)-specific siRNA inside the hydrophilic core. A preceding entrapment of superparamagnetic iron-oxide nanoparticles (Fex Oy-NPs) inside the niosomal bilayer structure was achieved in order to enhance the cellular uptake via an external magnetic manipulation. After verifying a highly effective entrapment of the siRNA, the resulting hybrid niosomes were administered to BT-474 cells in a combinational therapy with either erlotinib or trastuzumab and monitored regarding the induced apoptosis. The obtained results demonstrated that the nanocarrier successfully caused a downregulation of the LFG gene in BT-474 cells, which led to an increased efficacy of the chemotherapeutics compared to plainly added siRNA. Especially the application of an external magnetic field enhanced the internalization of siRNA, therefore increasing the activation of apoptotic signaling pathways. Considering the improved therapy outcome as well as the high encapsulation efficiency, the formulated hybrid niosomes meet the requirements for a cost-effective commercialization and can be considered as a promising candidate for future siRNA delivery agents.
Keywords
- Gene delivery, Hybrid nanoparticles, Magnetic targeting, Niosomes, SiRNA
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmaceutical Science
Sustainable Development Goals
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In: Pharmaceutics, Vol. 13, No. 3, 394, 03.2021.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - In-vitro application of magnetic hybrid niosomes
T2 - Targeted sirna-delivery for enhanced breast cancer therapy
AU - Maurer, Viktor
AU - Altin, Selin
AU - Seleci, Didem Ag
AU - Zarinwall, Ajmal
AU - Temel, Bilal
AU - Vogt, Peter M.
AU - Strauß, Sarah
AU - Stahl, Frank
AU - Scheper, Thomas
AU - Bucan, Vesna
AU - Garnweitner, Georg
N1 - Funding Information: Funding: We acknowledge support of this publication by the German Research Foundation and the Open Access Publication Funds of Technische Universität Braunschweig.
PY - 2021/3
Y1 - 2021/3
N2 - Even though the administration of chemotherapeutic agents such as erlotinib is clinically established for the treatment of breast cancer, its efficiency and the therapy outcome can be greatly improved using RNA interference (RNAi) mechanisms for a combinational therapy. However, the cellular uptake of bare small interfering RNA (siRNA) is insufficient and its fast degradation in the bloodstream leads to a lacking delivery and no suitable accumulation of siRNA inside the target tissues. To address these problems, non-ionic surfactant vesicles (niosomes) were used as a nanocarrier platform to encapsulate Lifeguard (LFG)-specific siRNA inside the hydrophilic core. A preceding entrapment of superparamagnetic iron-oxide nanoparticles (Fex Oy-NPs) inside the niosomal bilayer structure was achieved in order to enhance the cellular uptake via an external magnetic manipulation. After verifying a highly effective entrapment of the siRNA, the resulting hybrid niosomes were administered to BT-474 cells in a combinational therapy with either erlotinib or trastuzumab and monitored regarding the induced apoptosis. The obtained results demonstrated that the nanocarrier successfully caused a downregulation of the LFG gene in BT-474 cells, which led to an increased efficacy of the chemotherapeutics compared to plainly added siRNA. Especially the application of an external magnetic field enhanced the internalization of siRNA, therefore increasing the activation of apoptotic signaling pathways. Considering the improved therapy outcome as well as the high encapsulation efficiency, the formulated hybrid niosomes meet the requirements for a cost-effective commercialization and can be considered as a promising candidate for future siRNA delivery agents.
AB - Even though the administration of chemotherapeutic agents such as erlotinib is clinically established for the treatment of breast cancer, its efficiency and the therapy outcome can be greatly improved using RNA interference (RNAi) mechanisms for a combinational therapy. However, the cellular uptake of bare small interfering RNA (siRNA) is insufficient and its fast degradation in the bloodstream leads to a lacking delivery and no suitable accumulation of siRNA inside the target tissues. To address these problems, non-ionic surfactant vesicles (niosomes) were used as a nanocarrier platform to encapsulate Lifeguard (LFG)-specific siRNA inside the hydrophilic core. A preceding entrapment of superparamagnetic iron-oxide nanoparticles (Fex Oy-NPs) inside the niosomal bilayer structure was achieved in order to enhance the cellular uptake via an external magnetic manipulation. After verifying a highly effective entrapment of the siRNA, the resulting hybrid niosomes were administered to BT-474 cells in a combinational therapy with either erlotinib or trastuzumab and monitored regarding the induced apoptosis. The obtained results demonstrated that the nanocarrier successfully caused a downregulation of the LFG gene in BT-474 cells, which led to an increased efficacy of the chemotherapeutics compared to plainly added siRNA. Especially the application of an external magnetic field enhanced the internalization of siRNA, therefore increasing the activation of apoptotic signaling pathways. Considering the improved therapy outcome as well as the high encapsulation efficiency, the formulated hybrid niosomes meet the requirements for a cost-effective commercialization and can be considered as a promising candidate for future siRNA delivery agents.
KW - Gene delivery
KW - Hybrid nanoparticles
KW - Magnetic targeting
KW - Niosomes
KW - SiRNA
UR - http://www.scopus.com/inward/record.url?scp=85103487756&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics13030394
DO - 10.3390/pharmaceutics13030394
M3 - Article
AN - SCOPUS:85103487756
VL - 13
JO - Pharmaceutics
JF - Pharmaceutics
IS - 3
M1 - 394
ER -