Advanced hybrid silica nanoparticles with pH-responsive diblock copolymer brushes: optimized design for controlled doxorubicin loading and release in cancer therapy

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Abstract
This study delves into the development, characterization, and application of modified mesoporous silica nanoparticles (MSNs) for targeted drug delivery in cancer therapy. MSNs were functionalized with poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) and poly(glycidyl methacrylate) (PGMA), and further modified with cross-linkers DAE and Ornithine. Characterization using FT-IR, SEM, TEM, DLS, and XPS confirmed the successful surface modifications, revealing particle sizes primarily within the 63–94 nm range. The MSNs demonstrated a pH-responsive behavior, crucial for smart drug delivery. Loading and release studies using Doxorubicin (DOX) showed a controlled release, with an 8 μg mg−1 loading capacity. Cytotoxicity assays on Caco2 colon cancer cells revealed that unloaded nano-systems, at concentrations above 45 μM, resulted in approximately 60% cell death, indicating inherent anti-cancer properties. However, variations in cytotoxic effects were observed in drug-loaded MSNs, with some modifications showing reduced anti-cancer activity. These findings highlight the potential of MSNs in drug delivery and cancer treatment, emphasizing the importance of nanoparticle design in therapeutic efficacy.
Funding Information
  • King Saud University (RSP2024R238)

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