A pH-sensitive supramolecular nanosystem with chlorin e6 and triptolide co-delivery for chemo-photodynamic combination therapy  

作　　者：Yihan Wu Jingjing Li Xuemei Zhong Jinfeng Shi Yanfen Cheng Chenglin He Jiaxin Li Liang Zou Chaomei Fu Meiwan Chen Jinming Zhang Huile Gao 

机构地区：[1]School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China [2]Department of Pharmacology and Pharmacy,The University of Hong Kong,Hong Kong SAR,China [3]School of Food and Biological Engineering,Chengdu University,Chengdu 610106,China [4]Institute of Chinese Medical Sciences,University of Macao,Macao,China [5]West China School of Pharmacy,Sichuan University,Chengdu 610041,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2022年第2期206-218,共13页亚洲药物制剂科学（英文）

基　　金：supported by National Natural Science Foundation of China (No.81973662);Distinguished Young Scholar of Sichuan Provincial Science and Technology Department (No.2019JDJQ0049);111 Project (No.B18035)

摘　　要：The combination of Ce6,an acknowledged photosensitizer,and TPL,a natural anticancer agent,has been demonstrated as a useful strategy to reinforce the tumor growth suppression,as well as decrease the systemic side effects compared with their monotherapy.However,in view of the optimal chemo-photodynamic combination efficiency,there is still short of the feasible nanovehicle to steadily co-deliver Ce6 and TPL,and stimuli-responsively burst release drugs in tumor site.Herein,we described the synergistic antitumor performance of a pH-sensitive supramolecular nanosystem,mediated by the host–guest complexing betweenβ-CD and acid pH-responsive amphiphilic co-polymer mPEG-PBAE-mPEG,showing the shell–core structural micelles with the tightβ-CD layer coating.Both Ce6 and TPLwere facilely co-loaded into the spherical supramolecular NPs(TPL+Ce6/NPs)by one-step nanoprecipitation method,with an ideal particle size(156.0 nm),acid pH-responsive drug release profile,and enhanced cellular internalization capacity.In view of the combination benefit of photodynamic therapy and chemotherapy,as well as co-encapsulation in the fabricated pH-sensitive supramolecular NPs,TPL+Ce6/NPs exhibited significant efficacy to suppress cellular proliferation,boost ROS level,lower MMP,and promote cellular apoptosis in vitro.Particularly,fluorescence imaging revealed that TPL+Ce6/NPs preferentially accumulated in the tumor tissue area,with higher intensity than that of free Ce6.As expected,upon 650-nm laser irradiation,TPL+Ce6/NPs exhibited a cascade of amplified synergistic chemo-photodynamic therapeutic benefits to suppress tumor progression in both hepatoma H22 tumor-bearingmice and B16 tumor-bearingmice.More importantly,lower systemic toxicitywas found in the tumor-bearingmice treated with TPL+Ce6/NPs.Overall,the designed supramolecular TPL+Ce6/NPs provided a promising alternative approach for chemo-photodynamic therapy in tumor treatment.

关 键 词：TRIPTOLIDE Chemo-photodynamic pH-sensitive supramolecular Nanosystem CO-DELIVERY 

分 类 号：R943[医药卫生—药剂学]