Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 27, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.nano.2020.102194
Keywords
Gene therapy; Combination therapy; Nanoparticle-microbubble complex; Sonoporation; Tumor angiogenesis
Funding
- Korea Health Industry Development Institute (KHIDI) - Ministry of Health Welfare [HI15C2797]
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology, Republic of Korea [NRF-2016R1A6A1A03012845, NRF-2020R1A2B5B02001733]
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Recently, combination therapy has received much attention because of its highly therapeutic effect in various types of cancers. In particular, chemo-photodynamic combination therapy has been considered as an outstanding strategy. However, an abnormal increase in tumor angiogenesis caused by reactive oxygen species (ROS) generated during photodynamic therapy (PDT) has been reported. In this study, the complex of doxorubicin (DOX)-encapsulating anti-angiogenic small interfering RNA (siRNA) nanoparticle and chlorin e6 (Ce6)-encapsulating microbubble has been developed to suppress tumor angiogenesis. The first compartment, doxorubicin-encapsulating siRNA nanoparticle, was electrostatically coated using two biocompatible polymers to prevent the damage of genetic materials. The other part, Ce6-encapsulating microbubble, serves as an ultrasound-triggered local delivery system as well as a drug carrier. Both the in vitro and in vivo experimental results demonstrate successful inhibition of angiogenesis with a minimized damage of siRNAs caused by ROS as well as improved therapeutic effect by chemo-photodynamic-gene triple combination therapy using ultrasound-triggered local delivery. (c) 2020 Elsevier Inc. All rights reserved.
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