Aggregation-Induced Emission in Photodynamic Therapy Applications

Aggregation-induced emission (AIE) has emerged as a transformative principle in the design of next-generation photosensitisers for photodynamic therapy (PDT). Unlike conventional dyes that suffer from aggregation-caused quenching, AIE luminogens (AIEgens) exhibit intensified fluorescence and boosted reactive oxygen species (ROS) generation in the aggregated state. The unique photophysical characteristics of AIEgens facilitate simultaneous imaging and therapy, enabling real-time monitoring of subcellular localisation and therapeutic efficacy. Rational molecular engineering—through donor–acceptor modulation, heavy-atom incorporation or polymerisation—allows fine-tuning of singlet-triplet energy gaps, intersystem crossing rates and emission wavelengths, including the near-infrared region suited for deep-tissue applications. Targeting strategies have expanded from mitochondrial and lysosomal localisations to organelle-specific delivery, supporting precision medicine approaches in oncology and antimicrobial treatments. The global significance of AIE-based PDT lies in its low systemic toxicity, high spatial control and compatibility with two-photon excitation, which together promise minimally invasive interventions from dermatology to deep-seated tumour ablation.

Research from Nature Portfolio

Recent studies have demonstrated the power of organelle-targeted AIEgens in enhancing PDT outcomes. One notable example involves a Golgi-targeting AIE photosensitiser that enters cells via caveolin-mediated endocytosis and displays a remarkably high correlation with Golgi markers. Structural modification to reduce the singlet-triplet energy gap yields superior singlet oxygen generation, inducing Golgi fragmentation, activation of apoptotic cascades and robust tumour cell eradication. Comparative analyses reveal that this organelle-specific design outperforms non-targeted analogues despite similar ROS yields, underscoring the importance of subcellular precision for maximising therapeutic index.

Aggregation-Induced Emission in Photodynamic Therapy Applications publication trend

The graph below shows the total number of articles in aggregation-induced emission in photodynamic therapy applications across all publications each year (not limited to Nature Index journals).

Technical terms

Aggregation-induced emission (AIE): Phenomenon whereby certain luminogens become highly emissive when aggregated, thereby avoiding quenching effects common to traditional dyes.

Photosensitiser (PS): A molecule that, upon light absorption, transfers energy to molecular oxygen to produce reactive oxygen species for therapeutic action.

Reactive oxygen species (ROS): Highly reactive oxygen derivatives, including singlet oxygen, responsible for oxidative damage to target cells in PDT.

Singlet oxygen (1O2): An electronically excited form of oxygen generated by photosensitisers, central to inducing cell death in photodynamic therapy.

Intersystem crossing (ISC): Non-radiative transition between electronic states of different spin multiplicity, crucial for triplet state formation and ROS production.

Donor–acceptor modulation: Design strategy that varies electron-donating and electron-accepting units within a molecule to adjust photophysical properties and ROS yield.

Two-photon absorption: Simultaneous uptake of two photons of lower energy to excite a molecule, enabling deep-tissue imaging and reduced phototoxicity.

References

1. Tuning the singlet-triplet energy gap: a unique approach to efficient photosensitizers with aggregation-induced emission (AIE) characteristics. Chemical Science (2015).
2. Golgi apparatus-targeted aggregation-induced emission luminogens for effective cancer photodynamic therapy. Nature Communications (2022).
3. Aggregation-induced emission photosensitizer-based photodynamic therapy in cancer: from chemical to clinical. Journal of Nanobiotechnology (2022).
4. Highly efficient singlet oxygen generation, two-photon photodynamic therapy and melanoma ablation by rationally designed mitochondria-specific near-infrared AIEgens. Chemical Science (2020).
5. Activation of apoptosis by rationally constructing NIR amphiphilic AIEgens: surmounting the shackle of mitochondrial membrane potential for amplified tumor ablation. Chemical Science (2021).