Thiophene donor for NIR-II fluorescence imaging-guided photothermal/photodynamic/chemo combination therapy

Qiang Liu; Jiangwei Tian; Ye Tian; Qinchao Sun; Dan Sun; Dewen Liu; Feifei Wang; Haijun Xu; Guoliang Ying; Jigang Wang; Ali K Yetisen; Nan Jiang

doi:10.1016/j.actbio.2021.03.064

Thiophene donor for NIR-II fluorescence imaging-guided photothermal/photodynamic/chemo combination therapy

Acta Biomater. 2021 Jun:127:287-297. doi: 10.1016/j.actbio.2021.03.064. Epub 2021 Apr 6.

Authors

Qiang Liu¹, Jiangwei Tian², Ye Tian³, Qinchao Sun⁴, Dan Sun⁵, Dewen Liu⁶, Feifei Wang⁶, Haijun Xu⁷, Guoliang Ying⁸, Jigang Wang⁹, Ali K Yetisen¹⁰, Nan Jiang¹¹

Affiliations

¹ Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Department of Chemistry, Stanford University, CA 94305, United States.
² State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 21198, China.
³ Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China.
⁴ Guangdong Provincial Key Laboratory of Biomedical Optical Imaging Technology & Center for Biomedical Optics and Molecular Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
⁵ Jiangsu Co-innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Jiangsu Key Lab of Biomass-based Green Fuels and Chemicals, Nanjing Forestry University, Nanjing 210037, China.
⁶ Department of Chemistry, Stanford University, CA 94305, United States.
⁷ Jiangsu Co-innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Jiangsu Key Lab of Biomass-based Green Fuels and Chemicals, Nanjing Forestry University, Nanjing 210037, China. Electronic address: xuhaijun@njfu.edu.cn.
⁸ West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China; Brigham and Women's Hospital, Harvard Medical School, Cambridge, 02139 MA, United States. Electronic address: yingguoliang@gmail.com.
⁹ Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Department of Urology, Shenzhen People's Hospital (The First Affilated Hospital, Southern University of Science and Technology), Shenzhen, 518020, China. Electronic address: wangjigang@u.nus.edu.
¹⁰ Department of Chemical Engineering, Imperial College London, London, SW7 2AZ, United Kingdom.
¹¹ West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China; School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA. Electronic address: jiangnansophia@scu.edu.cn.

PMID: 33831570
DOI: 10.1016/j.actbio.2021.03.064

Abstract

Organic fluorophores/photosensitizers have been widely used in biological imaging and photodynamic and photothermal combination therapy in the first near-infrared (NIR-I) window. However, their applications in the second near-infrared (NIR-II) window are still limited primarily due to low fluorescence quantum yields (QYs). Here, a boron dipyrromethene (BDP) is created as a molecularly engineered thiophene donor unit with high QYs to the redshift. Thiophene insertion initiates substantial redshifts of the absorbance as compared to its counterparts in which iodine is introduced. The fluorescent molecule can be triggered by an NIR laser with a single wavelength, thereby producing emission in the NIR-II windows. Single NIR laser-triggered phototherapeutic nanoparticles (NPs) are developed by encapsulating the BDP and the chemotherapeutic drug docetaxel (DTX) by using a synthetic amphiphilic poly(styrene-co-chloromethyl styrene)-graft-poly(ethylene glycol) functionalized with folic acid (FA). These BDP-T-N-DTX-FA NPs not only show superior solubility and high singlet oxygen QY (Φ_Δ=62%) but also demonstrate single NIR laser-triggered multifunctional characteristics. After intravenous administration of the NPs into 4T1 tumor-bearing mice, the accumulation of the NPs in the tumor showed a high signal-to-background ratio (11.8). Furthermore, 4T1 tumors in mice were almost eradicated by DTX released from the BDP-T-N-DTX-FA NPs under single NIR laser excitation and the combination of photodynamic therapy (PDT) and photothermic therapy (PTT). STATEMENT OF SIGNIFICANCE: The application of organic photosensitizers is still limited primarily due to low fluorescence quantum yields (QYs) in the second near-infrared (NIR-II) window. Here, a boron dipyrromethene (BDP) as a molecularly engineered thiophene donor unit with high QYs to the redshift is created. Phototherapeutic nanoparticles (NPs) are developed by encapsulating the BDP and docetaxel (DTX) using a synthetic amphiphilic poly(styrene-co-chloromethyl styrene)-graft-poly(ethylene glycol) functionalized with folic acid (FA). These BDP-T-N-DTX-FA NPs not only show high singlet oxygen QY (Φ_Δ=62%) but also demonstrate single NIR laser-triggered multifunctional characteristics and a high signal-to-background ratio (11.8). Furthermore, 4T1 tumors in mice were almost eradicated by DTX released from the BDP-T-N-DTX-FA NPs under single NIR laser excitation and the PDT/PTT combination therapy.

Keywords: Molecular imaging; NIR-II fluorophore probe; Photothermal/photodynamic/chemo combination therapy; Single laser triggering; Thiophene donor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
Mice
Nanoparticles*
Optical Imaging
Photochemotherapy*
Photosensitizing Agents / pharmacology
Thiophenes / pharmacology

Substances

Photosensitizing Agents
Thiophenes