Toward Type I/II ROS Generation Photoimmunotherapy by Molecular Engineering of Semiconducting Perylene Diimide

• Published in: Advanced healthcare materials 2024-03, Vol.13 (8), p.e2303175-n/a
• Main Authors: Zhang, Jie, Ma, Wen, Luo, Haifen, Zhang, Kangxin, Lv, Jingqi, Jiang, Lizhi, Huang, Yanli, Song, Jibing, Yang, Zhen, Huang, Wei
• Format: Article
• Language: English
• Subjects: Antitumor activity; bioimaging; Bromides; Cancer; Cell death; Diimide; Emission; Hypoxia; Immune response; Immune system; Immunogenicity; Medical imaging; Near infrared radiation; Organic chemistry; perylene diimide; Photodynamic therapy; photoimmunotherapy; phototheranostics; Phototherapy; Reactive oxygen species; semiconducting nanoparticles; Tumor microenvironment; Tumors; type I photodynamic therapy
• ISSN: 2192-2640; 2192-2659; 2192-2659
• DOI: 10.1002/adhm.202303175

As prospective phototheranostic agents for cancer imaging and therapy, semiconducting organic molecule‐based nanomedicines are developed. However, near‐infrared (NIR) emission, and tunable type I (O2•−) and type II (1O2) photoinduced reactive oxygen species (ROS) generation to boost cancer photoimmunotherapy remains a big challenge. Herein, a series of D–π–A structures, NIR absorbing perylene diimides (PDIs) with heavy atom bromide modification at the bay position of PDIs are prepared for investigating the optimal photoinduced type I/II ROS generation. The heavy atom effect has demonstrated a reduction of molecular ∆EST and promotion of the intersystem crossing processes of PDIs, enhancing the photodynamic therapy (PDT) efficacy. The modification of three bromides and one pyrrolidine at the bay position of PDI (TBDT) has demonstrated the best type I/II PDT performance by batch experiments and theoretical calculations. TBDT based nanoplatforms (TBDT NPs) enable type I/II PDT in the hypoxic tumor microenvironment as a strong immunogenic cell death (ICD) inducer. Moreover, TBDT NPs showing NIR emission allow in vivo bioimaging guided phototherapy of tumor. This work uses novel PDIs with adjustable type I/II ROS production to promote antitumor immune response and accomplish effective tumor eradication, consequently offering molecular guidelines for building high‐efficiency ICD inducers. In this study, the authors proposes heavy‐atom effect on the perylene diimides (PDIs) enabling the regulation of molecular energy levels, thereby achieving the effective photoinduced generation of O2•− and 1O2 for cancer theranostics. This molecular engineering study on PDIs offers valuable guidance to the design of type I/II photodynamic agents and oxygen independent photoimmunotherapeutics for cancer.