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Designing NIR AIEgens for lysosomes targeting and efficient photodynamic therapy of tumors
Yuanhang Li1, Xing Wang1, Yongfei Zhao1
1School of Chemistry and Chemical Engineering, Southeast University, Nanjing, Jiangsu 211189, PR China.
Abstract:
Cancer is the most severe health problem facing most people today. Photodynamic therapy (PDT) for tumors has attracted attention because of its non-invasive nature, negligible adverse reactions, and high spatiotemporal selectivity. Developing biocompatible photosensitizers that can target, guide, and efficiently kill cancer cells is desirable in PDT. Here, two amphiphilic organic compounds, PS-I and PSS-II, were synthesized based on the D-π-A structure with a positive charge. The two AIEgens exhibited near-infrared emission, large Stokes shift, high 1O2 and O2-∙ generation efficiency, good biocompatibility, and photostability. They were co-incubated with cancer cells and eventually accumulated to lysosomes by cell imaging experiments. In vitro and in vivo experiments demonstrated that PS-I and PSS-II could effectively kill cancer cells and sufficiently inhibit tumor growth under light irradiation. PS-I had a higher fluorescence quantum yield in the aggregated state, which made it better for bio-imaging in imaging-guided photodynamic therapy. In contrast, PSS-II with a longer conjugated structure had more ROS generation to kill tumor cells under illumination, and the tumor growth inhibition of mice reached 71.95% during the treatment. No observable injury or undesirable outcomes were detected in the vital organs of the mice within the treatment group, suggesting that PSS-II/PS-I had a promising future in efficient imaging-guided PDT for cancer.
Insights
Two novel organic compounds, PS-I and PSS-II, show promise for imaging-guided photodynamic therapy (PDT) by effectively targeting and killing cancer cells with minimal side effects. These photosensitizers offer a potential new avenue for non-invasive cancer treatment.
Area of Science:
- Biomedical Engineering
- Materials Science
- Oncology
Background:
- Cancer remains a significant global health challenge.
- Photodynamic therapy (PDT) offers a non-invasive treatment option for tumors.
- Developing targeted, biocompatible photosensitizers is crucial for effective PDT.
Purpose of the Study:
- To synthesize and evaluate two novel amphiphilic organic compounds (PS-I and PSS-II) as photosensitizers for imaging-guided photodynamic therapy.
- To assess their biocompatibility, targeting capabilities, and efficacy in killing cancer cells both in vitro and in vivo.
- To investigate their potential for real-time imaging and therapeutic applications in cancer treatment.
Main Methods:
- Synthesis of D-π-A structured amphiphilic organic compounds (PS-I, PSS-II) with positive charges.
- Characterization of photophysical properties including near-infrared emission, Stokes shift, and reactive oxygen species (ROS) generation efficiency.
- Cell imaging experiments to determine cellular uptake and localization (lysosomes).
- In vitro and in vivo studies to evaluate cancer cell killing and tumor growth inhibition under light irradiation.
Main Results:
- PS-I and PSS-II demonstrated good biocompatibility, photostability, and efficient generation of singlet oxygen (1O2) and superoxide radicals (O2-∙).
- Cell imaging confirmed accumulation in lysosomes, indicating effective cellular targeting.
- In vitro and in vivo experiments showed significant cancer cell killing and tumor growth inhibition (up to 71.95% with PSS-II).
- PS-I excelled in bio-imaging due to higher fluorescence quantum yield, while PSS-II showed superior ROS generation for tumor eradication.
Conclusions:
- PS-I and PSS-II are effective photosensitizers for imaging-guided photodynamic therapy.
- PSS-II demonstrated potent tumor growth inhibition with no observable toxicity in vital organs.
- These compounds hold significant promise for developing advanced, targeted cancer therapies.
