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

• Published in: International journal of nanomedicine Vol. 15; pp. 2717 - 2732
• Main Authors: Liu, Yupeng, Dai, Suhuan, Wen, Lijuan, Zhu, Yun, Tan, Yanan, Qiu, Guoxi, Meng, Tingting, Yu, Fangying, Yuan, Hong, Hu, Fuqiang
• Format: Journal Article
• Language: English
• Published: New Zealand Dove 01.01.2020; Dove Medical Press
• Subjects: angiogenesis; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - pharmacology; Animals; Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Drug Delivery Systems - methods; dual-targeting; Endothelial Cells - drug effects; glioblastoma; Glioblastoma - pathology; Glioblastoma - therapy; glycolipid-like micelles; Glycolipids - chemistry; Humans; Indocyanine Green - administration & dosage; Indocyanine Green - chemistry; Mice, Nude; Micelles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Neovascularization, Pathologic - drug therapy; Oligopeptides - chemistry; Original Research; Photosensitizing Agents - administration & dosage; Photosensitizing Agents - pharmacology; phototherapy; Phototherapy - methods; Tissue Distribution; Xenograft Model Antitumor Assays; phototherapy; glioblastoma; glycolipid-like micelles; dual-targeting; angiogenesis
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S234240

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. 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. 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. 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.