Perfluorocarbon nanoparticles enhance reactive oxygen levels and tumour growth inhibition in photodynamic therapy.

Yuhao Cheng,Hao Cheng,Jinhui Wu,Kaikai Wang,Yiqiao Hu,Xuefeng Qiu,Wei Huan,Chenxiao Jiang,Ahu Yuan

doi:10.1038/ncomms9785

Abstract

Photodynamic therapy (PDT) kills cancer cells by converting tumour oxygen into reactive singlet oxygen (1O2) using a photosensitizer. However, pre-existing hypoxia in tumours and oxygen consumption during PDT can result in an inadequate oxygen supply, which in turn hampers photodynamic efficacy. Here to overcome this problem, we create oxygen self-enriching photodynamic therapy (Oxy-PDT) by loading a photosensitizer into perfluorocarbon nanodroplets. Because of the higher oxygen capacity and longer 1O2 lifetime of perfluorocarbon, the photodynamic effect of the loaded photosensitizer is significantly enhanced, as demonstrated by the accelerated generation of 1O2 and elevated cytotoxicity. Following direct injection into tumours, in vivo studies reveal tumour growth inhibition in the Oxy-PDT-treated mice. In addition, a single-dose intravenous injection of Oxy-PDT into tumour-bearing mice significantly inhibits tumour growth, whereas traditional PDT has no effect. Oxy-PDT may enable the enhancement of existing clinical PDT and future PDT design.

Highlights

Photodynamic therapy (PDT) kills cancer cells by converting tumour oxygen into reactive singlet oxygen (1O2) using a photosensitizer
As the oxygen self-enriching photodynamic therapy (Oxy-PDT) agent is irradiated by a near-infrared (NIR) 808-nm laser, IR780 transfers energy to the oxygen enriched in the PFH, producing cytotoxic singlet oxygen (Fig. 1a)
The existence of PFH in the Oxy-PDT agent was confirmed by the contrast enhancement in the ultrasound image, whereas LIP(IR780), pure PFH, and water produced blank echo signals (Fig. 1d)

Summary

Introduction

Photodynamic therapy (PDT) kills cancer cells by converting tumour oxygen into reactive singlet oxygen (1O2) using a photosensitizer. Pre-existing hypoxia in tumours and oxygen consumption during PDT can result in an inadequate oxygen supply, which in turn hampers photodynamic efficacy To overcome this problem, we create oxygen self-enriching photodynamic therapy (Oxy-PDT) by loading a photosensitizer into perfluorocarbon nanodroplets. The tumour oxygen content remains limited during PDT, sufficient O2 can always be enriched in the PFC droplet for photodynamic consumption by the loaded PS, obtaining improved efficacy (Fig. 1a) This type of enhancement is possible regardless of pre-existing hypoxia, photodynamic consumption, or vascular damage; it has been reported that the 1O2 lifetime in perfluorocarbon is much longer than in the cellular environment or in water[19], which results in long-lasting photodynamic effects. We envision that this new approach may guide improvements in the clinical use of PDT

Methods

Results

Conclusion