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Manufacture and Drug Delivery Applications of Silk Nanoparticles
Published on: October 8, 2016
Functionalized Mesoporous Silica Nanoparticles for Drug-Delivery to Multidrug-Resistant Cancer Cells
Nóra Igaz1, Péter Bélteky2, Dávid Kovács1,3
1Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary.
Background:
Multidrug resistance is a common reason behind the failure of chemotherapy. Even if the therapy is effective, serious adverse effects might develop due to the low specificity and selectivity of antineoplastic agents. Mesoporous silica nanoparticles (MSNs) are promising materials for tumor-targeting and drug-delivery due to their small size, relatively inert nature, and extremely large specific surfaces that can be functionalized by therapeutic and targeting entities. We aimed to create a fluorescently labeled MSN-based drug-delivery system and investigate their internalization and drug-releasing capability in drug-sensitive MCF-7 and P-glycoprotein-overexpressing multidrug-resistant MCF-7 KCR cancer cells.
Methods And Results:
To track the uptake and subcellular distribution of MSNs, particles with covalently coupled red fluorescent Rhodamine B (RhoB) were produced (RhoB@MSNs). Both MCF-7 and MCF-7 KCR cells accumulated a significant amount of RhoB@MSNs. The intracellular RhoB@MSN concentrations did not differ between sensitive and multidrug-resistant cells and were kept at the same level even after cessation of RhoB@MSN exposure. Although most RhoB@MSNs resided in the cytoplasm, significantly more RhoB@MSNs co-localized with lysosomes in multidrug-resistant cells compared to sensitive counterparts. To examine the drug-delivery capability of these particles, RhoB@Rho123@MSNs were established, where RhoB-functionalized nanoparticles carried green fluorescent Rhodamine 123 (Rho123) - a P-glycoprotein substrate - as cargo within mesopores. Significantly higher Rho123 fluorescence intensity was detected in RhoB@Rho123@MSN-treated multidrug-resistant cells than in free Rho123-exposed counterparts. The exceptional drug-delivery potential of MSNs was further verified using Mitomycin C (MMC)-loaded RhoB@MSNs (RhoB@MMC@MSNs). Exposures to RhoB@MMC@MSNs significantly decreased the viability not only of drug-sensitive but of multidrug-resistant cells and the elimination of MDR cells was significantly more robust than upon free MMC treatments.
Conclusion:
The efficient delivery of Rho123 and MMC to multidrug-resistant cells via MSNs, the amplified and presumably prolonged intracellular drug concentration, and the consequently enhanced cytotoxic effects envision the enormous potential of MSNs to defeat multidrug-resistant cancer.
Insights
Mesoporous silica nanoparticles (MSNs) effectively deliver chemotherapy drugs to multidrug-resistant cancer cells. This MSN-based drug delivery system enhances drug concentration and improves cancer cell death, offering a promising strategy against drug resistance.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Multidrug resistance (MDR) is a major obstacle in chemotherapy, leading to treatment failure.
- Conventional chemotherapeutic agents often lack specificity, causing severe side effects.
- Mesoporous silica nanoparticles (MSNs) offer a potential solution for targeted drug delivery due to their tunable properties and large surface area.
Purpose of the Study:
- To develop a fluorescently labeled MSN-based drug delivery system.
- To investigate the cellular uptake and intracellular distribution of MSNs in drug-sensitive and multidrug-resistant cancer cells.
- To evaluate the drug-releasing capability and therapeutic efficacy of MSNs in overcoming drug resistance.
Main Methods:
- Synthesized fluorescently labeled MSNs (RhoB@MSNs) for tracking cellular uptake.
- Investigated MSN internalization and subcellular localization in MCF-7 (sensitive) and MCF-7 KCR (MDR) cells.
- Loaded MSNs with Rhodamine 123 (Rho123) and Mitomycin C (MMC) to assess drug delivery efficacy in MDR cells.
Main Results:
- MSNs were efficiently internalized by both sensitive and MDR cancer cells.
- Intracellular MSN concentrations remained stable, with higher lysosomal co-localization in MDR cells.
- MSNs loaded with Rho123 and MMC demonstrated significantly enhanced delivery and cytotoxic effects in MDR cells compared to free drugs.
Conclusions:
- MSNs facilitate efficient delivery of therapeutic agents to multidrug-resistant cancer cells.
- The enhanced intracellular drug concentration via MSNs leads to improved cytotoxic effects.
- MSN-based drug delivery systems show significant potential for overcoming chemotherapy resistance in cancer treatment.
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