Chitosan-naphthalimide probes for dual channel recognition of HClO and H2S in cells and their application in photodynamic therapy

• Published in: International journal of biological macromolecules 2024-11, Vol.281 (Pt 4), p.136517, Article 136517
• Main Authors: Zhao, Bo, Liu, Jun, Zhu, Caiqiong, Cheng, Xinjian
• Format: Article
• Language: English
• Subjects: Cell imaging and PDT; Chitosan-based probes; HClO and H2S recognition
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.136517

The combination of bio-imaging with photodynamic therapy (PDT) to accomplish theranostics is promising in cancer treatment. Three chitosan-naphthalimide probes were studied in this work. 4-(5-Bromothiophen-2-yl)-1,8-naphthalic anhydride was first synthesized, and then reacted with chitosan to obtain the macromolecules (CS-N-Br). The recognition group thiomorpholine or its derivatives were introduced into CS-N-Br to obtain nano-probes (CS-N-ML, CS-N-BSZ, CS-N-FSQ) eventually. The studies revealed that CS-N-ML and CS-N-FSQ exhibit high selectivity and can specifically recognize HClO and H2S. CS-N-ML and CS-N-FSQ can perform exogenous and endogenous confocal imaging of HClO and H2S in cells also. CS-N-ML's ability to target lysosomes positions indicated it could act as a lysosome-specific probe. It was discovered that the probes generate superoxide anions (O2•−) via a Type I mechanism. This discovery endows the probes with high photosensitizing activity even under hypoxic conditions. There is a positive correlation between the extent of the conjugated system and the photosensitivity of the probes, indicating that an enhanced conjugation leads to increased photosensitivity. Upon light irradiation, the probes generate ROS within HeLa cells. These results suggested that these probes can achieve theranostics for diseases associated with abnormal levels of HClO and H2S. •Three novel macromolecular fluorescent probes were synthesized. They are capable of dual-channel recognition for HClO and H2S.•The probes are suitable for both exogenous and endogenous cellular imaging of HClO and H2S.•The probes exhibit high photosensitivity even at low light power densities and they can induce apoptosis in cells.•The probe generates O2•− through Type I photodynamic mechanism under light irradiation, thereby exhibiting high photosensitivity for PDT.