Gutian Zhang1, Wenting Cheng2, Lin Du3, Chuanjun Xu2, Jinlong Li4. 1. Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China. zhang.gutian@nju.edu.cn. 2. Department of Laboratory Medicine, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, China. 3. Department of Urology, Drum Tower Hospital, Medical School of Southeast University, Nanjing, 210008, China. 4. Department of Laboratory Medicine, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, China. lijinlong1028@126.com.
Abstract
BACKGROUND: Phototherapy 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. RESULTS: Near-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. CONCLUSION: This 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.
BACKGROUND: Phototherapy 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. RESULTS: Near-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. CONCLUSION: This 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.