Specific Light‐Up Bioprobe with Aggregation‐Induced Emission and Activatable Photoactivity for the Targeted and Image‐Guided Photodynamic Ablation of Cancer Cells

Abstract

Activatable photosensitizers (PSs) have been widely used for the simultaneous fluorescence imaging and photodynamic ablation of cancer cells. However, the ready aggregation of traditional PSs in aqueous media can lead to fluorescence quenching as well as reduced phototoxicity even in the activated form. We have developed a series of PSs that show aggregation-enhanced emission and phototoxicity and thus the exact opposite behavior to that of previously reported PSs. We further developed a dual-targeted enzyme-activatable bioprobe based on the optimized photosensitizer and describe simultaneous light-up fluorescence imaging and activated photodynamic therapy for specific cancer cells. The design of smart probes should thus open new opportunities for targeted and image-guided photodynamic therapy.

Activatable Photosensitizers: Agents for Selective Photodynamic Therapy

“…[82] Recently, Liu et al described a series of special fluorophores that possess aggregation-induced emission (AIE) characteristics that can be used advantageously in the design of new aPSs. [83][84][85] One system is a dual-selective enzyme-responsive bioprobe containing a PS for cancer-specific imaging and activatable PDT. [83] The probe is composed of four parts including an AIE fluorogen for imaging and PS, a GFLG peptide with cathepsin B responsive properties, a specific tri-Asp linker for improved hydrophilicity, and a cRGD-targeting group.…”

“…[83][84][85] One system is a dual-selective enzyme-responsive bioprobe containing a PS for cancer-specific imaging and activatable PDT. [83] The probe is composed of four parts including an AIE fluorogen for imaging and PS, a GFLG peptide with cathepsin B responsive properties, a specific tri-Asp linker for improved hydrophilicity, and a cRGD-targeting group. In aqueous media, the photoactivities of the probe are quenched by the absence of exciton energy induced by intramolecular motions.…”

“…Efficient fluorescence emission and phototoxicity is only obtained in the aggregate model induced by the tumor-related reactivation. [83] This system serves as a prototype of a design for constructing aPSs that are not composed of quenchers/scavengers or energy acceptors.…”

Cellular and Mitochondrial Dual‐Targeted Organic Dots with Aggregation‐Induced Emission Characteristics for Image‐Guided Photodynamic Therapy

“…These AIEgens such as tetraphenylethene (TPE) are propeller shaped, which emit almost no fl uorescence when molecularly dissolved but could be induced to become highly emissive in aggregate state due to the prohibition of energy dissipation and restriction of intramolecular rotation (RIR). [ 62,[67][68][69][70] The unique feature of AIEgens has made them valuable in the development of lightup probes, [ 13,[71][72][73] and ultrabright organic dots [74][75][76][77][78][79] for sensing and imaging applications. Very recently, we and others also found that several AIEgens show effi cient ROS production in aggregate state.…”

“…Very recently, we and others also found that several AIEgens show effi cient ROS production in aggregate state. [ 72,[80][81][82] These unique properties are ideal for mitochondria-targeted PDT as the accumulation of AIEgens in mitochondria or encapsulation of AIEgens by mitochondria-targeted nanocarriers will not compromise their fl uorescence and ROS generation.…”