Photodynamic therapy (
PDT) provides an alternative approach to targeted
cancer treatment, but the therapeutic mechanism of advanced nanodrugs applied to live cells and tissue is still not well understood. Herein, we employ the hybrid hyperspectral stimulated Raman scattering (SRS) and transient absorption (TA) microscopy developed for real-time in vivo visualization of the dynamic interplay between the unique photoswichable
lanthanide-doped upconversion nanoparticle-conjugated
rose bengal and
triphenylphosphonium (LD-UCNP@CS-Rb-TPP) probe synthesized and live
cancer cells. The Langmuir pharmacokinetic model associated with SRS/TA imaging is built to quantitatively track the uptakes and pharmacokinetics of LD-UCNP@CS-Rb-TPP within
cancer cells. Rapid SRS/TA imaging quantifies the endocytic internalization rates of the LD-UCNP@CS-Rb-TPP probe in individual HeLa cells, and the translocation of LD-UCNP@CS-Rb-TPP from mitochondria to cell nuclei monitored during
PDT can be associated with mitochondria fragmentations and the increased nuclear membrane permeability, cascading the dual organelle ablations in
cancer cells. The real-time SRS spectral changes of cellular components (e.
g., proteins,
lipids, and
DNA) observed reflect the
PDT-induced oxidative damage and the dose-dependent death pattern within a single live
cancer cell, thereby facilitating the real-time screening of optimal light dose and illumination duration controls in
PDT. This study provides new insights into the further understanding of drug delivery and therapeutic mechanisms of photoswitchable LD-UCNP nanomedicine in live
cancer cells, which are critical in the optimization of nanodrug formulations and development of precision
cancer treatment in
PDT.