Fluorescence lifetime imaging microscopy (FLIM): FLIM experiments were performed with custom-built, inverted confocal laser stage scanning microscopes. A 405 nm laser diode (LDH P-C-405, PicoQuant GmbH, Germany) and a supercontinuum laser (SuperK Extreme EXB-4, NKT Photonics) equipped with an acousto-optic tunable filter (AOTF SuperK SELECT UV/VIS-nIR, NKT Photonics) were employed as excitation sources. Both sources supply picosecond pulses with adjustable repetition rates ranging from 2 to 78 MHz. Focusing of the excitation laser and collection of scattered and emitted light was achieved with high numerical aperture oil immersion objective lenses (Zeiss Plan-Apochromat, 100x, 1.4 Oil DIC and alpha Plan-Fluar 100x/1,49 Oil M27, Carl Zeiss AG, Germany). Two additional long-pass filters (458 nm: RazorEdge LP Edge Filter 458 RU, Semrock; 532 nm: LP EdgeBasic™ Filter 532, Semrock) were introduced into the detection beam paths to exclude the detection of the excitation wavelength. Single photon avalanche diodes (SPAD; PDM series, Micro Photon Devices, Italy) with an active area of 100 µm coupled with time-correlated single photon counting electronics (HydraHarp 400, PicoQuant GmbH, Germany) were used to acquire time-resolved photoluminescence data. The SymPhoTime64 software package (PicoQuant GmbH, Germany) was used to acquire and analyze time-correlated single photon counting (TCSPC) data. Further data analysis and plotting were carried out using the opensource general-purpose programming language Python. Positioning, focusing, and determination of suitable acquisition parameters for each investigated cell was performed with low laser irradiance of 1.5 -2.5 μW/μm 2 to avoid damaging the cell prior to PDT induction. An irradiance between 5.5 μW/μm 2 and 8 μW/μm 2 was set for PDT initiation of hypericinincubated cell, whereas control cells were measured at a minimum irradiance of 8 μW/μm 2 up to 20 μW/μm 2 . The laser power was adjusted and regularly checked with a power meter (Optical power meter 1830-C Picowatt Digital, Newport) throughout the measurement session to ensure power stability. In total, 60 single cells were measured by FLIM for all incubation conditions to confirm all observations and ensure a high reproducibility (n = 60).