Acceptor-Donor-Acceptor-type Conjugated Oligomer Nanoparticles for Efficient Photothermal Antimicrobial Therapy

Infectious diseases caused by bacteria pose a serious threat to human health, and the emergence of antibiotic-resistant bacteria further weakens the advantages of traditional antibiotics in the treatment of infectious diseases. Therefore, the development of non-antibiotic treatment strategies to restrain the spread of bacterial resistance and the increase in mortality has become a major challenge that urgently needs to be addressed in the global public health field. In recent years, photothermal therapy has demonstrated unique advantages in the antibacterial field, and has become one of the most promising strategies for treating infectious diseases. Photothermal antibacterial therapy is a new strategy of antibacterial treatment that uses photothermal agents (PTAs) to convert near-infrared (NIR) light energy into local high heat, destroying nucleic acids, proteins, and membranes to achieve antibacterial effects. However, photothermal antibacterial therapy is currently limited by poor photothermal conversion efficiency, biosafety, and thermal stability, which severely hinder further clinical applications. Therefore, how to improve photothermal antibacterial activity and biosafety from material design of PTAs is still a major challenge.

Recently, Professor Shengliang Li of the School of Pharmaceutical Sciences, Soochow University, and Associate Professor Huanxiang Yuan of Beijing Technology and Business University, have published a research paper entitled “Molecular Evolution of Acceptor-Donor-Acceptor-type Conjugated Oligomer Nanoparticles for Efficient Photothermal Antimicrobial Therapy” in Advanced Functional Materials. The contribution investigated the importance of the electron-donating ability of donors in the design of photothermal agents based on the acceptor (A) -donor (D) -acceptor (A) type molecular backbones and developed a class of organic photothermal agents with high antibacterial activities in NIR window, achieving biosafety, high-efficiency antibacterial activities both in vitro and in vivo, including treatment of antibiotic-resistant bacterial infections.

In recent years, Li’s group has developed a series of NIR photothermal agents and achieved high-efficiency in vivo treatment of bacterial infections (Angew. Chem. Int. Ed.2021, 133, 11864; Angew. Chem. Int. Ed.2020, 59, 632). Based on the previous works, this study first coupled various electron donors and acceptors to synthesize a series of A-D-A type photothermal agents and coated with DSPE-PEG2000 to prepare water-soluble nanodrugs. The results show that the stronger the conjugation degree of the donors, the better its electron-donating ability, which can effectively promote the intramolecular charge transfer, and the photothermal conversion efficiency is also higher. Further results have shown that the activities of these nanodrugs in antibacterial and antibiotic-resistant bacterial infection treatment are also better. In addition, the use of high-performance photothermal agents will significantly reduce the dosage and the side effects caused by local high temperatures, improving the safety and clinical application potential.

The significance of this study lies in the design strategy of enhancing the photothermal conversion efficiency of agents by regulating the donors doped in molecular backbones, enhancing intramolecular charge transfer and NIR absorption, and thus providing new ideas for the development of photothermal agents suitable for clinical treatment of infectious diseases.

This work is supported by the National Natural Science Foundation of China, Jiangsu Specially Appointed Professorship, Leading Talents of Innovation and Entrepreneurship of Gusu, the Suzhou Science and Technology Program, and Beijing Technology and Business University Postgraduate Research Ability Enhancement Plan (2023).

Reference: Huanxiang Yuan, Zelin Li, Qi Zhao, Shaochuan Jia, Ting Wang, Li Xu, Haitao Yuan, Shengliang Li., Molecular Evolution of Acceptor-Donor-Acceptor-type Conjugated Oligomer Nanoparticles for Efficient Photothermal Antimicrobial Therapy. Adv. Funct. Mater.2023, 33, 2213209.

Linker：https://onlinelibrary.wiley.com/doi/10.1002/adfm.202213209

Prof. Shengliang Li is a distinguished professor at the College of Pharmaceutical Sciences at Soochow University and a principal investigator in the Advanced Bio-Photon and Nanomedicine laboratory. He has co-authored more than 100 papers with over 4600 times of citations (H-Index 38) and 4 ESI Highly Cited Papers (ESI 1%). Prof. Shengliang Li holds 4 PCT patent applications and received 4 Chinese patents. He is a Young Editorial Board Member for Chinese Chemical Letters. His research focuses on molecular design, nanotechnology engineering, and mechanistic studies of photoactive drugs and probes for enabling disease theranostics, chemical biology, and environmental health applications.