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Published on: September 17, 2013
Mannose modified zwitterionic polyester-conjugated second near-infrared organic fluorophore for targeted photothermal
Jiaxu Li1, Liuchun Zheng2, Chuncheng Li3
1Beijing National Laboratory for Molecular Sciences, Key Laboratory of Engineering Plastics, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, People's Republic of China. hubeizlc@iccas.ac.cn lichch@iccas.ac.cn and University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
Abstract:
Cancer resistance has been the huge challenge to clinical treatment. A photothermal therapy of second near-infrared (NIR-II) organic dye small molecule has been used to conquer the cancer resistance. However, the available NIR-II dye lacks selectivity and spreads throughout the body. It has toxicity and indiscriminate burn injuries normal cells and tissues during therapy. Hence, to improve the therapeutic outcomes, herein, for the first time, we report the mannose-modified zwitterionic nanoparticles loading IR1048 dye, aiming to overcome cancer cellular resistance. The targeting molecule mannose has been applied to modify zwitterionic polyester, and the obtained polyester is employed to load IR1048 to prolong the circulation time in the blood and improve the stability of loaded dye, due to the good cytocompatibility of polyester and the antifouling properties of zwitterions. In vitro experimental results show that the pH-responsive targeted nanoparticles display satisfactory photophysical properties, prominent photothermal conversion efficiency (44.07%), excellent photothermal stability, negligible cytotoxicity for normal cells and strong photothermal toxicity to drug-resistant cancer cells. Moreover, due to the mannose targeting effect, cancer cells can endocytose the nanoparticles effectively. All these results demonstrate potential application of this alternative hyperthermal delivery system with remote-controllable photothermal therapy of tumor for accurate diagnosis by NIR-II fluorescence imaging.
Insights
Mannose-modified nanoparticles loaded with IR1048 dye offer a targeted approach to overcome cancer resistance. This novel system enhances photothermal therapy efficacy while minimizing damage to healthy tissues.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Cancer resistance to therapy remains a significant clinical challenge.
- Second near-infrared (NIR-II) organic dyes show promise for photothermal therapy but lack selectivity and can cause off-target toxicity.
- Existing NIR-II dyes can spread throughout the body, leading to indiscriminate damage to normal cells and tissues.
Purpose of the Study:
- To develop a targeted drug delivery system to overcome cancer cellular resistance using mannose-modified zwitterionic nanoparticles loaded with an IR1048 dye.
- To improve the selectivity and reduce the toxicity of photothermal therapy.
- To enhance the therapeutic outcomes of cancer treatment through precise targeting and efficient drug delivery.
Main Methods:
- Mannose was used to modify zwitterionic polyester for nanoparticle formulation.
- IR1048 dye was loaded into the mannose-modified zwitterionic nanoparticles.
- In vitro experiments were conducted to evaluate photophysical properties, photothermal conversion efficiency, stability, cytotoxicity, and cellular uptake.
- pH-responsive and targeted nanoparticles were synthesized and characterized.
Main Results:
- The mannose-modified zwitterionic nanoparticles exhibited excellent photophysical properties and a high photothermal conversion efficiency of 44.07%.
- The nanoparticles demonstrated excellent photothermal stability, negligible cytotoxicity to normal cells, and potent photothermal toxicity against drug-resistant cancer cells.
- Effective endocytosis of nanoparticles by cancer cells was observed due to the mannose targeting effect.
- The nanoparticles showed prolonged circulation time and improved dye stability.
Conclusions:
- Mannose-modified zwitterionic nanoparticles represent a promising pH-responsive, targeted delivery system for photothermal therapy.
- This system effectively overcomes cancer cellular resistance and minimizes damage to healthy tissues.
- The developed nanoparticles offer potential for accurate tumor diagnosis via NIR-II fluorescence imaging and remote-controllable hyperthermal therapy.
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