Albumins constrainting the conformation of mitochondria-targeted photosensitizers for tumor-specific photodynamic therapy

Bin Fang; Hua Bai; Jiaxin Zhang; Limin Wang; PanPan Li; Yihao Ge; Hui Yang; Hui Wang; Bo Peng; Wenbo Hu; Huili Ma; Xi Chen; Li Fu; Lin Li

doi:10.1016/j.biomaterials.2024.122914

Albumins constrainting the conformation of mitochondria-targeted photosensitizers for tumor-specific photodynamic therapy

Biomaterials. 2024 Oct 22:315:122914. doi: 10.1016/j.biomaterials.2024.122914. Online ahead of print.

Authors

Bin Fang¹, Hua Bai², Jiaxin Zhang², Limin Wang², PanPan Li², Yihao Ge³, Hui Yang³, Hui Wang⁴, Bo Peng², Wenbo Hu², Huili Ma⁵, Xi Chen⁶, Li Fu⁷, Lin Li⁸

Affiliations

¹ Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University, Xi'an, 710072, China; State Key Laboratory of Solidification Processing, School of Materials Science and Engineering, Northwestern Polytechnical University, Xi'an, 710072, China.
² Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University, Xi'an, 710072, China.
³ Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, 710127, China.
⁴ Institute of Flexible Electronics (IFE, Future Technologies), Xiamen University, Xiamen, 361102, China.
⁵ Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing, 211816, China.
⁶ Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, 710127, China. Electronic address: [email protected].
⁷ State Key Laboratory of Solidification Processing, School of Materials Science and Engineering, Northwestern Polytechnical University, Xi'an, 710072, China. Electronic address: [email protected].
⁸ Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University, Xi'an, 710072, China; Institute of Flexible Electronics (IFE, Future Technologies), Xiamen University, Xiamen, 361102, China; Future Display Institute in Xiamen, Xiamen, 361005, China. Electronic address: [email protected].

PMID: 39461059
DOI: 10.1016/j.biomaterials.2024.122914

Abstract

Tumor ablation Preclinical organelle-targeted phototherapies have effectively achieved tumor photoablation for regenerative biomedical applications in cancer therapies. However, engineering effective phototherapy drugs with precise tumor-localization targeting and organelle direction remains challenging. Herein, we report a albumins constrainting mitochondrial-targeted photosensitizer nanoparticles (PSs@BSAs) for tumor-specific photodynamic therapy. X-ray crystallography elucidates the two-stage assembly mechanism of PSs@BSAs. Femtosecond transient absorption spectroscopy and quantum mechanical calculations reveal the implications of conformational dynamics at the excited state. PSs@BSAs can efficiently disable mitochondrial activity, and further disrupt tumor angiogenesis based on the photodynamic effect. This triggers a metabolic and oxidative stress crisis to facilitate photoablation of solid tumor and antitumor metastasis. The study fully elucidates the interdisciplinary issues of chemistry, physics, and biological interfaces, thereby opening new horizons to inspire the engineering of organelle-targeted tumor-specific photosensitizers for biomedical applications.

Keywords: Mitochondria-targeted; Photosensitizer; Phototherapy; Two-stage assembly.