Stimuli-Responsive Upconversion Nanoparticles-Embedded Mesoporous SiO2 Nanospheres for Delivery of Hydrophilic and Hydrophobic Anticancer Drugs and Cellular Imaging

Core-shell architectures are widely reported for enhancing the luminescence properties of upconversion nanoparticles (UCNPs) by minimizing surface quenching and optimizing energy transfer pathways. However, this study demonstrates a hybrid structure in which UCNPs (CaF₂:Yb³⁺, Er³⁺) are embedded in a mesoporous silica (m-SiO₂) nanosphere using a soft chemical approach, offering an alternative to conventional core-shell structures. The structural analysis by X-ray diffraction (XRD) and transmission electron microscopy (TEM) confirmed the successful entrapment of highly crystalline cubic phase fluorite-type UCNPs in a mesoporous SiO₂ framework (UCNPs@m-SiO₂). These UCNPs@m-SiO₂ exhibited a high surface area, porous nature, good colloidal stability, and pH-dependent charge-converting characteristics, which made them extremely conducive for drug delivery application. This matrix-based design not only stabilizes the nanoparticles but also significantly enhances their upconversion luminescence properties upon near-infrared (NIR) light irradiation (980 nm). Furthermore, the porous nature of the silica matrix allows efficient encapsulation of anticancer drugs, doxorubicin hydrochloride (DOX) and curcumin (CUR), and demonstrates their sustained and controlled pH-responsive release with higher release in a mildly acidic environment. The-drug loaded systems showed enhanced toxicity toward breast (MCF-7) and lung (A549) cancer cells over their individual counterparts (DOX and CUR). Moreover, the developed UCNPs@m-SiO₂ retained their red emission capability upon internalization into cancer cells and thus can also be used for cellular imaging purposes. Specifically, this work demonstrated the development of water-dispersible, biocompatible, and photostable UCNPs for image-guided drug delivery applications.