Imaging-guided photodynamic control of autophagy-apoptosis switching in breast cancer using hypericin-functionalized upconverting nanoparticles.

Poly(N,N-dimethylacrylamide-co-2-aminoethyl acrylate)-coated core-shell NaYF4:Yb3+,Er3+@NaYF4:Nd3+ upconverting nanoparticles (UCNPs) functionalized with cyanine dye and hypericin were developed as a dual-purpose nanocarriers for simultaneous photodynamic therapy (PDT) and bioimaging of SKBR3 breast cancer cells. The nanoparticles efficiently transported photosensitizers into cells, enabling spatiotemporal control of intracellular localisation and photoactivation. Confocal and fluorescence lifetime imaging analyses confirmed nanoparticle uptake, distribution, and Förster resonance energy transfer between the cyanine dye and hypericin. Upon near-infrared irradiation, the system induced a light-driven switch between autophagy and apoptosis, validated by biochemical and imaging assays. Western blot and caspase-3 activation demonstrated pathway-specific responses depending on the formulation and irradiation conditions. Moreover, the proposed surface-engineered particles possess the potential for enhanced lymphatic targeting. This study highlights the capacity of multifunctional UCNP-based nanoplatforms to mediate controlled therapeutic responses and improve selectivity in breast cancer treatment.