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Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Selenium-incorporated mesoporous silica nanoparticles for osteosarcoma therapy
Lei He1, Pamela Habibovic1, Sabine van Rijt1
1Department of Instructive Biomaterials Engineering, MERLN Institute for Technology Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. s.vanrijt@maastrichtuniversity.nl.
Abstract:
Selenium (Se) compounds are promising chemotherapeutics due to their ability to inhibit cancer cell activity via the generation of reactive oxygen species (ROS). However, to circumvent adverse effects on bone healthy cells, new methods are needed to allow intracellular Se delivery. Mesoporous silica nanoparticles (MSNs) are promising carriers for therapeutic ion delivery due to their biocompability, rapid uptake via endocytosis, and ability to efficiently incorporate ions within their tunable structure. With the aim of selectively inhibiting cancer cells, here we developed three types of MSNs and investigated their ability to deliver Se. Specifically, MSNs containing SeO32- loaded on the surface and in the pores (MSN-SeL), SeO32- doped in the silica matrix (Se-MSNs) and Se nanoparticles (SeNP) coated with mesoporous silica (SeNP-MSNs), were successfully synthesized. All synthesized nanoparticles were stable in neutral conditions but showed rapid Se release in the presence of glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH). Furthermore, all nanoparticles were cytotoxic towards SaoS-2 cells and showed significantly lower toxicity towards healthy osteoblasts, where Se doped MSNs showed lowest toxicity towards osteoblasts. We further show that the nanoparticles could induce ROS and cell apoptosis. Here we demonstrate MSNs as promising Se delivery carriers for osteosarcoma (OS) therapy.
Insights
Mesoporous silica nanoparticles effectively deliver selenium compounds to inhibit osteosarcoma cells. These nanoparticles show selective toxicity, sparing healthy bone cells, and induce cancer cell death via reactive oxygen species.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapeutics
Background:
- Selenium compounds show promise as chemotherapeutics by generating reactive oxygen species (ROS) to inhibit cancer cell activity.
- Targeted intracellular delivery of selenium is crucial to minimize adverse effects on healthy bone cells.
- Mesoporous silica nanoparticles (MSNs) offer biocompatibility, endocytosis-driven uptake, and tunable structures for efficient therapeutic ion delivery.
Purpose of the Study:
- To develop and investigate MSNs for selective intracellular delivery of selenium (Se) to inhibit osteosarcoma (OS) cells.
- To synthesize and characterize three distinct MSN formulations for Se delivery: surface-loaded (MSN-SeL), doped (Se-MSNs), and silica-coated nanoparticles (SeNP-MSNs).
- To evaluate the efficacy and safety profile of these Se-loaded MSNs in targeting cancer cells while sparing healthy osteoblasts.
Main Methods:
- Synthesis and characterization of three types of selenium-loaded MSNs (MSN-SeL, Se-MSNs, SeNP-MSNs).
- Assessment of Se release profiles under physiological conditions, particularly in the presence of glutathione (GSH) and NADPH.
- Evaluation of nanoparticle cytotoxicity towards SaoS-2 osteosarcoma cells and healthy osteoblasts.
- Investigation of ROS generation and apoptosis induction in cancer cells treated with the synthesized nanoparticles.
Main Results:
- All synthesized MSN formulations demonstrated stability in neutral conditions and rapid Se release in the presence of GSH and NADPH.
- The nanoparticles exhibited significant cytotoxicity towards SaoS-2 cells, with notably lower toxicity towards healthy osteoblasts.
- Se-doped MSNs (Se-MSNs) displayed the lowest toxicity towards osteoblasts among the tested formulations.
- The MSNs successfully induced ROS production and promoted apoptosis in osteosarcoma cells.
Conclusions:
- MSNs are effective carriers for intracellular selenium delivery, offering a promising strategy for osteosarcoma therapy.
- The developed MSN formulations exhibit selective cytotoxicity, targeting cancer cells while minimizing harm to healthy bone cells.
- The ability of MSNs to induce ROS and apoptosis underscores their potential as targeted chemotherapeutic agents for osteosarcoma.
