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Updated: Jun 25, 2025
Photodynamic Therapy with Blended Conducting Polymer/Fullerene Nanoparticle Photosensitizers
Published on: October 28, 2015
A structure-guided strategy to design Golgi apparatus-targeted type-I/II aggregation-induced emission
Xing Zhao1, Xi Wu1, Ranran Shang1
1State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Abstract:
The Golgi apparatus (GA) is a vital target for anticancer therapy due to its sensitivity against reactive oxygen species (ROS)-induced oxidative stress that could lead to cell death. In this study, we designed a series of aggregation-induced emission (AIE)-based photosensitizers (TPAPyTZ, TPAPyTC, TPAPyTM, and TPAPyTI) carrying different ROS with selective GA-targeted ability. The in vitro study showed that TPAPyTZ and TPAPyTC displayed strong AIE characteristics, robust type-I/II ROS production capabilities, specific GA-targeted, high photostability, and high imaging quality. The cell-uptake of TPAPyTZ was found primarily through an energy-dependent caveolae/raft-mediated endocytosis pathway. Remarkably, TPAPyTZ induced GA-oxidative stress, leading to GA fragmentation, downregulation of GM130 expression, and activation of mitochondria caspase-related apoptosis during photodynamic therapy (PDT). In vivo experiments revealed that TPAPyTZ significantly inhibited tumor proliferation under lower-intensity white light irradiation with minimal side effects. Overall, our work presents a promising strategy for designing AIEgens for fluorescence imaging-guided PDT. Additionally, it enriched the collection of GA-targeted leads for the development of cancer theranostics capable of visualizing dynamic changes in the GA during cancer cell apoptosis, which could potentially enable early diagnosis applications in the future. STATEMENT OF SIGNIFICANCE: AIE luminogens (AIEgens) are potent phototheranostic agents that can exhibit strong fluorescence emission and enhance ROS production in the aggregate states. In this study, through the precise design of photosensitizers with four different electron-acceptors, we constructed a series of potent AIEgens (TPAPyTZ, TPAPyTC, TPAPyTM, and TPAPyTI) with strong fluorescence intensity and ROS generation capacity. Among them, TPAPyTZ with an extended π-conjugation displayed the strongest ROS generation ability and anti-tumor activity, resulting in an 88 % reduction in tumor weight. Our studies revealed that the enhanced activity of TPAPyTZ may be due to its unique Golgi apparatus (GA)-targeted ability, which causes GA oxidative stress followed by effective cancer cell apoptosis. This unique GA-targeted feature of TPAPyTZ remains rare in the reported AIEgens, which mainly target organelles such as lysosome, mitochondria, and cell membrane. The successful design of a GA-targeted and potent AIEgen could enrich the collection of GA-targeted luminogens, providing a lead theranostic for the further development of fluorescence imaging-guided PDT, and serving as a tool to explore the potential mechanism and discover new GA-specific drug targets.
Insights
Researchers developed novel aggregation-induced emission (AIE) photosensitizers targeting the Golgi apparatus (GA) for cancer therapy. TPAPyTZ demonstrated potent anticancer activity by inducing GA oxidative stress and apoptosis during photodynamic therapy (PDT).
Area of Science:
- Materials Science: Design and synthesis of novel aggregation-induced emission (AIE) luminogens (AIEgens).
- Biomedical Engineering: Development of theranostic agents for cancer imaging and therapy.
- Cell Biology: Investigation of cellular mechanisms, including oxidative stress and apoptosis.
Background:
- The Golgi apparatus (GA) is a sensitive target for anticancer therapy due to its susceptibility to reactive oxygen species (ROS).
- Aggregation-induced emission (AIE) luminogens (AIEgens) are promising phototheranostic agents due to their enhanced fluorescence and ROS production in aggregate states.
- Targeting specific organelles like the GA offers a unique strategy for cancer treatment.
Purpose of the Study:
- To design and synthesize novel AIE-based photosensitizers with selective Golgi apparatus (GA) targeting ability.
- To evaluate the efficacy of these AIEgens in producing ROS, inducing GA oxidative stress, and mediating photodynamic therapy (PDT) for cancer treatment.
- To explore the potential of GA-targeted AIEgens for fluorescence imaging-guided cancer theranostics and early diagnosis.
Main Methods:
- Synthesis of a series of AIE-based photosensitizers (TPAPyTZ, TPAPyTC, TPAPyTM, TPAPyTI) with varying electron acceptors.
- In vitro evaluation of AIE characteristics, ROS production, GA targeting, photostability, and imaging quality.
- In vivo studies to assess tumor inhibition and side effects under white light irradiation.
Main Results:
- TPAPyTZ and TPAPyTC exhibited strong AIE properties, efficient ROS generation, specific GA targeting, and high imaging quality.
- TPAPyTZ induced Golgi apparatus oxidative stress, leading to fragmentation, GM130 downregulation, and apoptosis activation during PDT.
- TPAPyTZ significantly inhibited tumor proliferation in vivo with minimal side effects, showing an 88% reduction in tumor weight.
Conclusions:
- The developed GA-targeted AIEgen, TPAPyTZ, is a potent agent for fluorescence imaging-guided photodynamic therapy (PDT).
- This study provides a promising strategy for designing AIEgens and enriches the collection of GA-targeted theranostic leads for cancer therapy.
- GA-targeted AIEgens offer potential for visualizing dynamic changes during cancer cell apoptosis, aiding in early diagnosis applications.
