Folic acid-functionalized mesoporous silica nanoparticles integrating fluorouracil-derived carbon dots and porphyrin for targeted breast cancer chemo-photodynamic therapy

Abstract

We developed herein a new nanoplatform, MSNCDs-FA@TMPyP, for combined chemotherapy and photodynamic cancer therapy. The platform is built on mesoporous silica nanoparticles (MSN) with integrated 5-fluorouracil-derived carbon dots (FU CDs), serving as a dual-function system. Folic acid (FA) was added for targeted delivery to cancer cells, which often have high folate receptor concentrations. Finally, a tetrakis(N-methylpyridinium-4-yl) porphyrin (TMPyP) photosensitizer was loaded onto the platform to complete the chemo-photodynamic system. Comprehensive characterization (including TEM, EDX mapping, FTIR, XPS, and UV-vis spectroscopy) confirmed the structure. The synthesized MSNCDs were spherical (100–200 nm), with successful integration of FU CDs into the MSN particles, a finding strongly supported by EDX mapping and XPS. Functionalization with TMPyP and FA was verified by FTIR, Zeta potential, DLS, and UV-vis spectroscopy. The loading capacity of TMPyP is 333.3 mg g⁻¹. For acidic tumour environments, this drug-releasing nanoplatform is pH responsive (89% at pH 5.0, 55% at pH 7.4). Kinetic modelling suggests a synergistic diffusion and matrix erosion process for TMPyP release, with Higuchi (R² = 0.99 for pH 5, R² = 0.98 for pH 7.4) and Korsmeyer–Peppas mechanisms (R² = 0.9696 for pH 5, R² = 0.957 for pH 7.4), with release exponents of n = 0.3617 and n = 0.384 for pH 5, 7.4, respectively. The nanoplatform has a selectivity index of 8.44 and a 9-fold increase in cytotoxicity upon light activation for MDA-MB-231 cells. The nanoplatform MSNCDs-FA@TMPyP generated 41.12% early apoptosis, 22.07% late apoptosis, and 5.31% primary necrosis in MDA-MB-231 breast cancer cells upon light activation. This research presents a promising new bifunctional nanocomposite that combines the benefits of targeted chemotherapy and photodynamic therapy, offering a synergistic approach to cancer treatment that could lead to improved outcomes.