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Enhancing Drug Delivery for Overcoming Angiogenesis and Improving the Phototherapy Efficacy of Glioblastoma by ICG-Loaded Glycolipid-Like Micelles

Authors Liu Y, Dai S, Wen L, Zhu Y, Tan Y, Qiu G, Meng T, Yu F, Yuan H, Hu F

Received 11 October 2019

Accepted for publication 16 March 2020

Published 22 April 2020 Volume 2020:15 Pages 2717—2732


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Lei Yang

Yupeng Liu,1 Suhuan Dai,1 Lijuan Wen,1,2 Yun Zhu,3 Yanan Tan,3 Guoxi Qiu,1 Tingting Meng,1 Fangying Yu,1 Hong Yuan,1 Fuqiang Hu1

1College of Pharmaceutical Science, Zhejiang University, Hangzhou 310058, People’s Republic of China; 2National Engineering Research Center for Modernization of Traditional Chinese Medicine - Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou 342700, People’s Republic of China; 3Ocean College, Zhejiang University, Zhoushan 316021, Republic of China

Correspondence: Fuqiang Hu
College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, People’s Republic of China
Tel/Fax +86-571-88208439

Background: Phototherapy is a potential new candidate for glioblastoma (GBM) treatment. However inadequate phototherapy due to stability of the photosensitizer and low target specificity induces the proliferation of neovascular endothelial cells for angiogenesis and causes poor prognosis.
Methods: In this study, we constructed c(RGDfk)-modified glycolipid-like micelles (cRGD-CSOSA) encapsulating indocyanine green (ICG) for dual-targeting neovascular endothelial cells and tumor cells, and cRGD-CSOSA/ICG mediated dual effect of PDT/PTT with NIR irradiation.
Results: In vitro, cRGD-CSOSA/ICG inhibited cell proliferation and blocked angiogenesis with NIR irradiation. In vivo, cRGD-CSOSA/ICG exhibited increased accumulation in neovascular endothelial cells and tumor cells. Compared with that of CSOSA, the accumulation of cRGD-CSOSA in tumor tissue was further improved after dual-targeted phototherapy pretreatment. With NIR irradiation, the tumor-inhibition rate of cRGD-CSOSA/ICG was 80.00%, significantly higher than that of ICG (9.08%) and CSOSA/ICG (42.42%). Histological evaluation showed that the tumor vessels were reduced and that the apoptosis of tumor cells increased in the cRGD-CSOSA/ICG group with NIR irradiation.
Conclusion: The cRGD-CSOSA/ICG nanoparticle-mediated dual-targeting phototherapy could enhance drug delivery to neovascular endothelial cells and tumor cells for anti-angiogenesis and improve the phototherapy effect of glioblastoma, providing a new strategy for glioblastoma treatment.

Keywords: angiogenesis, dual-targeting, glycolipid-like micelles, phototherapy, glioblastoma

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