Theranostics 2018; 8(11):3059-3073. doi:10.7150/thno.23885

Research Paper

Temperature-controlled, phase-transition ultrasound imaging-guided photothermal-chemotherapy triggered by NIR light

Wei Li#1, Wanqing Hou#1, Xiaomeng Guo1, Lihua Luo1, Qingpo Li1, Chunqi Zhu1, Jie Yang1, Jiang Zhu2, Yongzhong Du1, Jian You1✉

1. College of Pharmaceutical Sciences, Zhejiang University, Yuhangtang Road 866, Hangzhou 310058, People's Republic of China
2. Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, People's Republic of China
# These authors contributed equally to this work.

Abstract

Recently, nano-sized ultrasound contrast agents encapsulating drugs for cancer diagnosis and therapy have attracted much attention. However, the ultrasound signal of these agents is too weak to obtain an ideal ultrasound imaging effect. Furthermore, conventional ultrasound contrast agents with strong echo signal are not suitable for drug delivery against cancer because of their large size. To circumvent this problem, phase-transition ultrasound contrast agents are believed to be an excellent choice.

Methods: Liposomes co-encapsulating doxorubicin (DOX), hollow gold nanospheres (HAuNS), and perfluorocarbon (PFC) were synthesized by film dispersion method. The morphology, particle size, and stability of these liposomes (DHPL) were investigated. The photothermal effect, drug release, particle size change, cytotoxicity, and ultrasound imaging were studied by using the near infrared (NIR) light. Furthermore, tumor accumulation of DHPL was observed by in vivo fluorescence imaging and the antitumor effect was verified in a 4T1 tumor model.

Results: The nanosystem displayed a homogeneous size distribution (~200 nm) and an efficient light-to-heat conversion effect under 808 nm NIR laser irradiation. The nanometer size enabled considerable accumulation of DHPL in the tumor sites. The localized hyperthermia resulting from the photothermal effect of HAuNS could trigger the size transformation of DHPL followed by significant DOX release. Due to the gasification of PFC, a remarkably enhanced ultrasound signal was detected. DHPL also exhibited a prominent photothermally reinforced chemotherapeutic effect under the control of NIR light both in vitro and in vivo. Importantly, no systemic toxicity was observed by DHPL treatment.

Conclusion: In this study, we fabricated multi-functional perfluorocarbon liposomes for ultrasound imaging-guided photothermal chemotherapy which have the potential to serve as a prospective cancer treatment approach.

Keywords: Hollow gold nanospheres, Perfluorocarbon, NIR light, Ultrasound imaging, Photothermal-chemotherapy

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How to cite this article:
Li W, Hou W, Guo X, Luo L, Li Q, Zhu C, Yang J, Zhu J, Du Y, You J. Temperature-controlled, phase-transition ultrasound imaging-guided photothermal-chemotherapy triggered by NIR light. Theranostics 2018; 8(11):3059-3073. doi:10.7150/thno.23885. Available from http://www.thno.org/v08p3059.htm