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An NIR-II Excitable AIE Small Molecule with Multimodal Phototheranostic Features for Orthotopic Breast Cancer
Shanliang Song1,2,3, Yue Zhao2, Miaomiao Kang1
1Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Material Science and Engineering, Shenzhen University, Shenzhen, 518060, China.
Abstract:
One-for-all phototheranostics, referring to a single component simultaneously exhibiting multiple optical imaging and therapeutic modalities, has attracted significant attention due to its excellent performance in cancer treatment. Benefitting from the superiority in balancing the diverse competing energy dissipation pathways, aggregation-induced emission luminogens (AIEgens) are proven to be ideal templates for constructing one-for-all multimodal phototheranostic agents. However, to this knowledge, the all-round AIEgens that can be triggered by a second near-infrared (NIR-II, 1000-1700 nm) light have not been reported. Given the deep tissue penetration and high maximum permissible exposure of the NIR-II excitation light, herein, this work reports for the first time an NIR-II laser excitable AIE small molecule (named BETT-2) with multimodal phototheranostic features by taking full use of the advantage of AIEgens in single molecule-facilitated versatility as well as synchronously maximizing the molecular donor-acceptor strength and conformational distortion. As formulated into nanoparticles (NPs), the high performance of BETT-2 NPs in NIR-II light-driven fluorescence-photoacoustic-photothermal trimodal imaging-guided photodynamic-photothermal synergistic therapy of orthotopic mouse breast tumors is fully demonstrated by the systematic in vitro and in vivo evaluations. This work offers valuable insights for developing NIR-II laser activatable one-for-all phototheranostic systems.
Insights
Researchers developed a novel aggregation-induced emission (AIE) small molecule, BETT-2, for one-for-all phototheranostics. This molecule, activated by second near-infrared (NIR-II) light, enables multimodal imaging and synergistic cancer therapy.
Area of Science:
- Biomedical Engineering
- Materials Science
- Nanotechnology
Background:
- One-for-all phototheranostics offer simultaneous imaging and therapy using a single agent.
- Aggregation-induced emission luminogens (AIEgens) are ideal for multimodal phototheranostics due to their emission properties.
- Second near-infrared (NIR-II) light offers deep tissue penetration and high safety for biomedical applications.
Purpose of the Study:
- To develop the first NIR-II laser-excitable AIE small molecule for multimodal phototheranostics.
- To investigate the potential of AIEgens in creating versatile, single-component phototheranostic agents.
- To evaluate the efficacy of the developed agent in cancer treatment.
Main Methods:
- Synthesized a novel NIR-II excitable AIE small molecule (BETT-2).
- Formulated BETT-2 into nanoparticles (NPs) for enhanced delivery and performance.
- Conducted in vitro and in vivo evaluations for imaging and therapeutic efficacy.
Main Results:
- BETT-2 NPs demonstrated efficient fluorescence, photoacoustic, and photothermal properties under NIR-II laser excitation.
- Achieved trimodal imaging-guided synergistic photodynamic and photothermal therapy.
- Successfully treated orthotopic mouse breast tumors with high efficacy.
Conclusions:
- BETT-2 represents a novel class of NIR-II activatable AIEgens for one-for-all phototheranostics.
- The developed nanoparticles show significant potential for advanced cancer theranostics.
- This study provides a foundation for developing next-generation NIR-II laser-driven phototheranostic systems.

