Synergy of hypoxia relief and heat shock protein inhibition for phototherapy enhancement

Gutian Zhang,Wenting Cheng,Lin Du,Chuanjun Xu,Jinlong Li

doi:10.1186/s12951-020-00749-5

Abstract

BackgroundPhototherapy is a promising strategy for cancer therapy by reactive oxygen species (ROS) of photodynamic therapy (PDT) and hyperthermia of photothermal therapy (PTT). However, the therapeutic efficacy was restricted by tumor hypoxia and thermal resistance of increased expression of heat shock protein (Hsp). In this study, we developed albumin nanoparticles to combine hypoxia relief and heat shock protein inhibition to overcome these limitations for phototherapy enhancement.ResultsNear-infrared photosensitizer (IR780) and gambogic acid (GA, Hsp90 inhibitor) were encapsulated into albumin nanoparticles via hydrophobic interaction, which was further deposited MnO2 on the surface to form IGM nanoparticles. Both in vitro and in vivo studies demonstrated that IGM could catalyze overexpress of hydrogen peroxide to relive hypoxic tumor microenvironment. With near infrared irradiation, the ROS generation was significantly increase for PDT enhancement. In addition, the release of GA was promoted by irradiation to bind with Hsp90, which could reduce cell tolerance to heat for PTT enhancement. As a result, IGM could achieve better antitumor efficacy with enhanced PDT and PTT.ConclusionThis study develops a facile approach to co-deliver IR780 and GA with self-assembled albumin nanoparticles, which could relive hypoxia and suppress Hsp for clinical application of cancer phototherapy.

Highlights

Phototherapy has attracted great attention for cancer treatment due to its high selectivity with laser irradiation [1, 2]
Various formulations of MnO2 have been reported to catalyze the overexpression of H2O2, which could in situ produce O 2 and generate more reactive oxygen species (ROS) for photodynamic therapy (PDT) cancer treatment [15]
Taking all advantages into consideration, in this study, we developed self-assembled albumin nanoparticles (IGM) to encapsulate IR780 (NIR photosensitizer) and Gambogic acid (GA) (Hsp90 inhibitor), which were further combined with MnO2 in the surface of nanoparticles with one-pot method (Fig. 1a)

Summary

Introduction

Phototherapy has attracted great attention for cancer treatment due to its high selectivity with laser irradiation [1, 2]. Hypoxia is the main characteristic of tumor microenvironment, which limited therapeutic efficacy of the highly oxygen (O2)-dependent PDT [10, 11]. Phototherapy is a promising strategy for cancer therapy by reactive oxygen species (ROS) of photodynamic therapy (PDT) and hyperthermia of photothermal therapy (PTT). The therapeutic efficacy was restricted by tumor hypoxia and thermal resistance of increased expression of heat shock protein (Hsp). We developed albumin nanoparticles to combine hypoxia relief and heat shock protein inhibition to overcome these limitations for phototherapy enhancement

Methods

Results

Conclusion