Modulating\nAggregation and Deaggregation Based on\nAssembling Strategy to Switch on NIR-II Light-Excited Fluorescence\nfor Self-Reporting Viability of Eliminating Cancer Cell

The fabrication of self-reporting photosensitizers (PSs),\nenabling\nreal-time evaluation of the extent of elimination of cancer cells,\nholds significant scientific importance in the photodynamic therapy\n(PDT) process. To address the intrinsic challenge of the short-wavelength\nlight source, this work proposed an innovative approach of rational\ndesign second near-infrared (NIR-II, 1000–1700 nm) light-excited\nfluorescent PS systems (named <b>HOEt-PI</b>, <b>Me-PI</b>, and <b>Et-PI</b>, respectively) through modulating aggregation\nand deaggregation based on assembling strategy. Therein, the suitable\ninterplanar distance of adjacent <b>Et-PI</b> linked with C–H···π\ninteractions was an idea for relieving compact π···π\npacking for fluorescent imaging as well as elevating the spin–orbit\ncoupling for reactive oxygen species (ROS) generation. With ROS continuously\nincreasing, <b>Et-PI</b> underwent cell membrane-to-mitochondria\nmigration, ultimately accumulated in nucleoli, symbolizing programmed\ncell death, thus distinguishing dead/live cells via three-photon fluorescence\nimaging (excited on 1250 nm) under photogeneration ROS. Meaningfully,\nthe three-photon fluorescence of <b>Et-PI</b> was triggered\nby RNA of nucleoli, for which the higher signal-to-noise ratio and\nin-depth fluorescence imaging observed cancer cellular viability.\nCollectively, the proposed findings presented a constructing strategy\nfor NIR-II light-mediated self-reporting PS for guiding the PDT of\ndeep cancerous tissue in the future.