Upconversion nanoparticle-mediated targeted drug delivery and photodynamic therapy for enhanced lung cancer treatment

The uncontrolled release of pharmaceuticals in traditional drug delivery systems has resulted in the development of innovative drug delivery methods based on nanotechnology and the use of tailored nanocarriers for cancer treatment. This study aimed to develop a targeted drug delivery system and photodynamic therapy (PDT) for enhanced therapeutic efficacy in lung cancer treatment. Upconversion nanoparticles (UCNPs) were synthesised via a Polyol route and surface-modified with polyethylene glycol (PEG) to improve biocompatibility. Further functionalization with folic acid (FA) facilitated targeted delivery to the human lung fibroblast cell line (MRC-5) (normal) and the human lung carcinoma cell line (A549) (lung cancer). The nanoparticles were loaded with paclitaxel (PTX), which inhibits microtubule polymerisation, forming UCNPs-FA-PTX complexes. Transmission Electron Microscopy (TEM) characterisation revealed well-dispersed nanoparticles with an average size of 22.5 ± 8.67 nm. Zeta potential analysis confirmed a shift from +24.5 mV for UCNPs to -14 mV for UCNPs-FA-PTX, indicating successful drug loading and surface modification. Dynamic Light Scattering (DLS) showed a larger particle size for drug-loaded UCNPs, with a mean diameter of 117 nm. Cell viability and apoptosis were evaluated using MTT and Flow cytometry assays. The UCNPs-FA-PTX complex demonstrated a significantly reduced A549 cell viability, with a half-maximal inhibitory concentration (IC 50) of 11.15 μg ml^-1at 72 h, compared to MRC-5 cells (IC 50 =22.8 μg ml^-1), and induced higher apoptosis in cancer cells. The study integrates PDT, using Tetraphenylporphyrin (TPP) as a dye to enhance treatment. Laser treatment (980 nm) enhanced these effects through a synergistic therapeutic approach. In contrast, UCNPs-FA and UCNPs exhibited minimal cytotoxicity, underscoring their biocompatibility.