Specific photothermal therapy to the tumors with high EphB4 receptor expression.
Photothermal therapy (PTT) employs photo-absorbing agents to generate heat from optical energy, leading to the 'burning' of tumor cells. Real-time imaging of in vivo distribution of photothermal agents and monitoring of post-treatment therapeutic outcomes are very important to design and optimize personalized PTT treatment. In this work, we used chitosan-stearic acid copolymer (CSO-SA) to encapsulate hollow gold nanospheres (HAuNS) and near-infrared (NIR) fluorescent tracer, DiR. Then, the surface of nanoparticles was further conjugated with a peptide (TNYL), which facilitates EphB4-positive tumor targeting delivery. Using a paired tumor mode in vivo and a double tumor-cell co-culture strategy in vitro, we demonstrated the feasibility of increasing the accumulation of our nanoparticles (DiR loaded and TNYL-CSO-SA coated HAuNS (DTCSH)) into EphB4-positive tumors through interaction between TNYL-peptide on the nanoparticles and EpHB4 receptors on tumor cells. When combined with NIR laser irradiation, our nanoparticles induced more EphB4-positive tumor cells death in vitro. We further developed optical imaging to temporally and spatially monitor the biodistribution of DTCSH. Under NIR laser irradiation, PTT exhibited dramatically stronger antitumor effect against EphB4-positive tumors than EphB4-negative tumors. This was attributed to enhanced accumulation of our nanoparticles in EphB4-positive tumors.
College of Pharmaceutical Sciences, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058, People's Republic of China.
Zuhua
Z
Wang
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, People's Republic of China.
Jihong
J
Sun
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Qinchun Road 79, Hangzhou 31003, People's Republic of China.
Yunqing
Y
Qiu
College of Pharmaceutical Sciences, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058, People's Republic of China.
Wei
W
Li
College of Pharmaceutical Sciences, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058, People's Republic of China.
Xiaomeng
X
Guo
College of Pharmaceutical Sciences, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058, People's Republic of China.
Qingpo
Q
Li
College of Pharmaceutical Sciences, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058, People's Republic of China.
Hanbo
H
Zhang
College of Pharmaceutical Sciences, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058, People's Republic of China.
Jialin
J
Zhou
College of Pharmaceutical Sciences, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058, People's Republic of China.
Yongzhong
Y
Du
College of Pharmaceutical Sciences, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058, People's Republic of China.
Hong
H
Yuan
College of Pharmaceutical Sciences, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058, People's Republic of China.
Fuqiang
F
Hu
College of Pharmaceutical Sciences, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058, People's Republic of China. Electronic address: youjiandoc@zju.edu.cn.
Jian
J
You
D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D005456:Fluorescent Dyes; D006046:Gold / Q000008:administration & dosage* / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D008856:Microscopy, Fluorescence / Q000379:methods; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D036081:Receptors, Eph Family / Q000378:metabolism*; D000068936:Theranostic Nanomedicine / Q000379:methods; D016896:Treatment Outcome
D005456:Fluorescent Dyes; D017319:Photosensitizing Agents; D006046:Gold; D036081:Receptors, Eph Family
EphB4 receptor; Hollow gold nanospheres; Irradiation safety; Optical imaging; Photothermal therapy