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

## TL;DR

Researchers developed a new photodynamic therapy agent that works better in low-oxygen tumor environments by combining a photosensitizer, a targeting molecule, and an oxygen-carrying compound.

## Contribution

A novel method for creating oxygen-carrying, membrane-targeting photodynamic therapy nanocomplexes that function effectively under hypoxic conditions.

## Key findings

- PLY-1/2/3 nanocomplexes efficiently generate singlet oxygen in both normoxic and hypoxic conditions.
- O2-loaded PLY-1 showed enhanced PDT efficacy and higher apoptosis rates compared to non-O2-loaded versions.
- The method provides a general approach for designing hypoxia-targeted photodynamic therapy composites.

## 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.

Photodynamic therapy (PDT) offers exceptional spatial and temporal precision, minimal invasiveness, and negligible side effects.