TY - JOUR
T1 - pH- and redox-sensitive selenium-incorporated mesoporous silica nanoparticles for osteosarcoma-targeted treatment
AU - He, L.
AU - Javid Anbardan, Z.
AU - Habibovic, P.
AU - van Rijt, S.
N1 - Funding Information:
This research was financially supported by the Gravitation Program \u201CMaterials Driven Regeneration\u201D, funded by the Dutch Research Council (NWO) (024.003.013). During the preparation of this work the author(s) used ChatGPT version 4o in order to refine text for improved readability. After using this tool, the author(s) reviewed and edited the content as needed and took full responsibility for the content of the publication.
Publisher Copyright:
© 2025 The Author(s)
PY - 2025/5/1
Y1 - 2025/5/1
N2 - Elevating oxidative stress presents a promising osteosarcoma (OS) treatment strategy, as it can selectively induce cell death in OS cells. Selenium nanoparticles (SeNPs) and doxorubicin (Dox) have shown promise in this regard by effectively upregulating oxidative stress. However, limitations, such as nanoparticle aggregation, inefficient intracellular uptake, and high-dose toxicity, hinder their therapeutic potential. Stimuli-responsive release can address these issues by enhancing effectiveness and minimizing side effects. In this paper, stimuli-responsive release of SeNPs/Dox for enhanced OS therapy is investigated. The introduction of a mesoporous silica coating (MS) onto SeNPs (SeMS) was used to prevent aggregation and allow for Dox co-encapsulation. The MS surface was further functionalized with hyaluronic acid (HA) using disulfide bonds (to create SeMSDox-SS-HA), to function as a gatekeeper and to enable pH- and redox-responsive release. Our results demonstrate low pH and elevated GSH levels can activate SeMSDox-SS-HA, resulting in rapid Dox/Se release within OS cells. Moreover, SeMSDox-SS-HA show significantly heightened OS inhibition, attributed to the differential reactive oxygen species (ROS) production and glutathione (GSH) depletion within OS cells, while hMSCs remained unaffected. These findings suggest that this pH/GSH-responsive MS delivery system encapsulating SeNPs and Dox represents a promising nanoplatform for OS-selective therapy through redox modulation.
AB - Elevating oxidative stress presents a promising osteosarcoma (OS) treatment strategy, as it can selectively induce cell death in OS cells. Selenium nanoparticles (SeNPs) and doxorubicin (Dox) have shown promise in this regard by effectively upregulating oxidative stress. However, limitations, such as nanoparticle aggregation, inefficient intracellular uptake, and high-dose toxicity, hinder their therapeutic potential. Stimuli-responsive release can address these issues by enhancing effectiveness and minimizing side effects. In this paper, stimuli-responsive release of SeNPs/Dox for enhanced OS therapy is investigated. The introduction of a mesoporous silica coating (MS) onto SeNPs (SeMS) was used to prevent aggregation and allow for Dox co-encapsulation. The MS surface was further functionalized with hyaluronic acid (HA) using disulfide bonds (to create SeMSDox-SS-HA), to function as a gatekeeper and to enable pH- and redox-responsive release. Our results demonstrate low pH and elevated GSH levels can activate SeMSDox-SS-HA, resulting in rapid Dox/Se release within OS cells. Moreover, SeMSDox-SS-HA show significantly heightened OS inhibition, attributed to the differential reactive oxygen species (ROS) production and glutathione (GSH) depletion within OS cells, while hMSCs remained unaffected. These findings suggest that this pH/GSH-responsive MS delivery system encapsulating SeNPs and Dox represents a promising nanoplatform for OS-selective therapy through redox modulation.
KW - Doxorubicin
KW - Dual stimuli-responsive release
KW - Glutathione depletion
KW - Reactive oxygen species production
KW - Selenium nanoparticles
U2 - 10.1016/j.matdes.2025.113883
DO - 10.1016/j.matdes.2025.113883
M3 - Article
SN - 0264-1275
VL - 253
JO - Materials & design
JF - Materials & design
M1 - 113883
ER -