Engineering ε-polylysine-based photodynamic therapy agents with oxygen carrying and membrane-targeting capabilities for enhanced therapy under hypoxic conditions

Abstract

Photodynamic therapy (PDT) offers exceptional spatial and temporal precision, minimal invasiveness, and negligible side effects. However, the hypoxic microenvironment of tumors greatly limits the effectiveness of conventional photodynamic therapy (PDT) and severely reduces its therapeutic efficiency. Here, a simple and versatile method for the preparation of PDT nanocomplexes based on ε-polylysine (PLY-1/2/3) was developed. By covalently combining a photosensitiser 5,10,15,20-tetra (4-carboxyl phenyl) porphyrin (H₂TCPP), a biotin-targeting moiety (D-Bio) and an O₂-carrying agent, perfluorohexanoic acid (PF-HA), the nanocomplex achieved specific targeting of HeLa cell membranes and was capable of efficiently generating cytotoxic singlet oxygen (¹O₂) in both normoxic and hypoxic conditions. Furthermore, O₂-loaded PLY-1 had enhanced PDT efficacy, and it also showed a higher degree of apoptosis than the non-O₂-loaded one. The results provided a facile and general method for the design and preparation of PDT composite against hypoxia.