Doxorubicin- and Selenium-Incorporated Mesoporous Silica Nanoparticles as a Combination Therapy for Osteosarcoma
Lei He1, Zahra Javid Anbardan1, Pamela Habibovic1
1Department of Instructive Biomaterials Engineering, MERLN Institute for Technology Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Abstract:
Doxorubicin (Dox) is a promising anticancer chemotherapeutic, which has been widely investigated in osteosarcoma (OS) treatment. However, there are several disadvantages regarding its clinical use. Specifically, Dox has low specificity toward cancer cells, which can lead to serious side effects. In addition, cancer cells can develop resistance toward Dox, reducing its therapeutic efficiency. Combination therapy (CT) facilitated by nanoparticle delivery systems is a promising strategy to overcome these drawbacks. In this study, we investigated the effectiveness of Dox and selenium (Se) CT using mesoporous silica nanoparticles (MSN) coated with hyaluronic acid (HA) as drug carriers. We hypothesized that combining Se as a second agent can increase Dox anti-OS effectiveness and that MSN can be used to facilitate dual drug delivery. In our system, HA was used as a gatekeeper to control the intracellular release of Se/Dox by means of its pH-responsive degradation. CT therapy using MSNs coated with HA led to a higher OS inhibitory efficiency in vitro compared to MSNs carrying either Se or Dox alone. This study demonstrates that using MSNs for the dual delivery of Se and Dox is a promising method for OS therapy.
Insights
This study shows that combining doxorubicin (Dox) and selenium (Se) using hyaluronic acid-coated mesoporous silica nanoparticles (MSN) effectively inhibits osteosarcoma (OS) growth in vitro, overcoming Dox resistance and side effects.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Doxorubicin (Dox) is a key chemotherapy for osteosarcoma (OS), but faces challenges like low specificity and drug resistance.
- Combination therapy (CT) using nanoparticle delivery systems offers a strategy to enhance efficacy and reduce side effects.
Purpose of the Study:
- To evaluate the combined efficacy of Dox and selenium (Se) for OS treatment using a novel nanoparticle system.
- To investigate the role of mesoporous silica nanoparticles (MSN) coated with hyaluronic acid (HA) in facilitating dual drug delivery and controlled release.
Main Methods:
- Doxorubicin and selenium were loaded into mesoporous silica nanoparticles (MSN).
- MSN were coated with hyaluronic acid (HA) to act as a pH-responsive gatekeeper for controlled intracellular drug release.
- The in vitro efficacy of the dual-drug delivery system was assessed in osteosarcoma cells.
Main Results:
- The combination therapy (CT) using HA-coated MSNs demonstrated significantly higher osteosarcoma (OS) inhibitory efficiency compared to MSNs carrying Dox or Se alone.
- The HA coating facilitated pH-responsive degradation, enabling controlled intracellular release of both Dox and Se.
- The dual-drug delivery system showed enhanced anti-OS activity in vitro.
Conclusions:
- Mesoporous silica nanoparticles (MSN) coated with hyaluronic acid (HA) are effective carriers for dual delivery of Doxorubicin (Dox) and selenium (Se).
- This combination therapy strategy shows promise for overcoming Dox resistance and improving osteosarcoma (OS) treatment outcomes.
