Photoactivated Lysosomal Escape of a Monofunctional Pt^II Complex Pt‐BDPA for Nucleus Access

Abstract

A photosensitizing monofunctional Pt complex, Pt‐BDPA, was prepared with a BODIPY chromophore. Apart from its DNA binding ability, this complex displays emission at ca. 578 nm and a singlet oxygen quantum yield of 0.133. Confocal imaging revealed that this complex was sequestered in lysosomes via endocytosis in the dark, preventing its access to the nucleus. Profiting from its photoinduced ROS generation ability, this complex undergoes lysosomal escape to access the nucleus upon photoirradiation. The photoinduced ROS still cause a drop in intracellular GSH, favoring the stability of Pt‐BDPA and contributing to its nuclear DNA accessibility. This complex displayed distinct cytotoxicity to all tested tumor cell lines upon photoirradiation, and the IC50 values were ca. 3–6 μm, which are distinctly lower than those found with only dark incubation (IC50>50 μm). These results are consistent with photoactivated lysosomal escape of this photosensitizing Pt complex to access the nucleus.

Multiple‐Color Platinum Complex with Super‐Large Stokes Shift for Super‐Resolution Imaging of Autolysosome Escape

“…[5,16a, 18] These suggest that Pt 2 L has significant photoactivated cytotoxicity,and can improve tumor specificity by selectively irradiating the tumor tissue for tumor treatment. Compared with the reported Pt-BDPAutilizing lysosome sequestration for platinum complex silencing as prodrug, [5] we verified that autolysosomes also can be used for platinum complex sequestration, further opening up new ways for the design of this kind of platinum complexes.S ince autophagy plays av ery important role in tumor and shows environmentally dependent, the real-time…”

“…As shown in Figure S17, with the increase of irradiation time,t he 2',7'-dichlorofluorescein (DCF) fluorescence increased and Pt 2 L gradually escaped to the nucleus,which suggested that the escape behavior of Pt 2 L was associated with its ROSp roduction and the damage of autolysosomes (Figure 6d), and was consistent with the reported mechanism. [5,18] Fort he first time,w eo bserved an ew transportation path that am atter flux escapes from autolysosomes to nucleus upon light stimulation.…”

“…Pt 2 L showed the behavior of photoactivated escaping from autolysosomes to nucleus and interacting with DNA, which had the potential of controllable nuclear accessibility and DNAb inding with photo-selectivity to improve the treatment specificity for tumor. [5,16] To validate this,t he intracellular behavior and cytotoxicity of Pt 2 L were further investigated. By observing the intracellular distribution of Pt 2 L within 30 h, we found that Pt 2 L can effectively enter the cytoplasm of living A549 cells in 2h,a nd can remain in the cytoplasm for over 30 hw ithout entering the nucleus (Figure S18).…”

“…[3] Currently,d ifferent approaches have been developed to improve tumor specificity of platinum drugs to mitigate their side effects,including modification of targeting groups or nanoparticles through active/passive targeting drug delivery,oxidation of bivalent platinum to non-toxic tetravalent platinum prodrugs and combination therapy. [4] Previously,H ea nd his colleagues [5] exploited aP t II drug that enters lysosomes via endocytosis and can be isolated in the cytoplasm, so as to avoid toxicity and side effects.B yl ight activation, the Pt II drug escapes from the lysosome to the nucleus and attacks DNAt os pecifically kill the tumor cells. In addition to lysosomes,a utolysosomes can also sequester drugs in the cytoplasm, which can provide additional avenues for platinum drugs silencing as prodrug to mitigate their side effects.…”

Systematic Research and Evaluation Models of Nanomotors for Cancer Combined Therapy

“…In order to investigate the possible mechanism of motion effect from nanomotors on cell-to-cell transmission and the intracellular distribution of nanomotors was also studied. We labeled lysosomes (the first barrier faced by nanoparticles after entering cells), [41] nucleus (the main location where…”