Abstract
Photosensitizers (PSs) with multiple characteristics, including efficient singlet oxygen (1O2) generation, cancer cell-selective accumulation and subsequent mitochondrial localization as well as near-infrared (NIR) excitation and bright NIR emission, are promising candidates for imaging-guided photodynamic therapy (PDT) but rarely concerned. Herein, a simple rational strategy, namely modulation of donor–acceptor (D–A) strength, for molecular engineering of mitochondria-targeting aggregation-induced emission (AIE) PSs with desirable characteristics including highly improved 1O2 generation efficiency, NIR emission (736 nm), high specificity to mitochondria, good biocompatibility, high brightness and superior photostability is demonstrated. Impressively, upon light irradiation, the optimal NIR AIE PS (DCQu) can generate 1O2 with efficiency much higher than those of commercially available PSs. The excellent two-photon absorption properties of DCQu allow two-photon fluorescence imaging of mitochondria and subsequent two-photon excited PDT. DCQu can selectively differentiate cancer cells from normal cells without the aid of extra targeting ligands. Upon ultralow-power light irradiation at 4.2 mW cm−2, in situ mitochondrial photodynamic activation to specifically damage cancer cells and efficient in vivo melanoma ablation are demonstrated, suggesting superior potency of the AIE PS in imaging-guided PDT with minimal side effects, which is promising for future precision medicine.
Highlights
Cancer is a well-recognized major public health problem and will become a leading cause of morbidity and mortality in the coming decades worldwide.[1]
Upon ultralow-power light irradiation at 4.2 mW cmÀ2, in situ mitochondrial photodynamic activation to damage cancer cells and efficient in vivo melanoma ablation are demonstrated, suggesting superior potency of the aggregation-induced emission (AIE) PS in imaging-guided photodynamic therapy (PDT) with minimal side effects, which is promising for future precision medicine
An alternatively strategy was proposed to improve the intersystem crossing (ISC) by decreasing the energy gap (DEst) between S1 and T1 based on the separation of the orbital distribution of the highest occupied molecular orbitals (HOMOs) and the lowest unoccupied molecular orbitals (LUMOs).[43]
Summary
Cancer is a well-recognized major public health problem and will become a leading cause of morbidity and mortality in the coming decades worldwide.[1]. Photosensitizers (PSs) with multiple characteristics, including efficient singlet oxygen (1O2) generation, cancer cell-selective accumulation and subsequent mitochondrial localization as well as near-infrared (NIR) excitation and bright NIR emission, are promising candidates for imaging-guided photodynamic therapy (PDT) but rarely concerned.
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