Rational Designing of Hypocrellin B-Loaded Mesoporous Silicia-NaYF ₄ @NaSmF ₄ Core@Shell Upconversion Nanoparticles for Targeted In Vitro Breast Cancer Therapy

Breast cancer, the second leading cause of death among women globally, presents challenges to conventional treatments. To combat this, researchers are more interested in developing minimally invasive alternative treatments and have emerged with a potential photodynamic treatment (PDT). To enhance the PDT efficacy and explore its potential in biological applications, materials such as upconversion nanoparticles (UCNPs) are being utilized. In this context, a combination of mesoporous silica core-shell UCNPs (mSi-CS-UCNPs: mSi-NaYF₄@NaSmF₄) loaded with Hypocrellin B (HB) was successfully synthesized via a layer-by-layer method (hydrothermal and coprecipitation methods). The structural and morphological studies of the synthesized HB-loaded mSi-CS-UCNPs were performed by XRD, FESEM, and HRTEM. The HB content was determined by RP-HPLC with peak detection at 254 nm and 3.8 min retention time. The in vitro release profile for HB, α-, and αβ-HB-mSi-CS-UCNPs gives 4.87, 38.9, and 56.47% of HB release at 72 h, respectively. The α and αβ phases of HB-mSi-CS-UCNPs under 980 nm near-infrared (NIR) light irradiation show 39 and 42% cell viability with a 29 μg/mL IC₅₀ value on 24 h treatment, which is less compared to that of the blank and HB-mSi-CS-UCNPs without light irradiation. Consequently, the reactive oxygen species (ROS) assay, cell apoptosis assay, and mitochondrial membrane potential (ΔΨ_m) of HB-loaded mSi-CS-UCNPs-treated MCF-7 breast cancer cells under 980 nm light irradiation also show better results, which represent higher singlet oxygen (¹O₂) production, leading to late apoptotic cells and features a decrease of ΔΨ_m by ROS generation. These results indicate that the HB-mSi-CS-UCNPs can effectively activate the loaded photosensitizers in the presence of 980 nm NIR light irradiation and produce ¹O₂ for cancer cell death by either apoptosis or necrosis and could be used as a therapeutic modality for the treatment of breast cancers.