Liposomal IR-780 as a Highly Stable Nanotheranostic Agent for Improved Photothermal/Photodynamic Therapy of Brain Tumors by Convection-Enhanced Delivery
1
Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou, Kwei-San, Taoyuan 33305, Taiwan
2
College of Medicine, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan
3
Center for Biomedical Science and Engineering, National Tsing Hua University, Hsinchu 300044, Taiwan
4
Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan
5
Department of Plastic and Reconstructive Surgery and Craniofacial Research Center, Chang Gung Memorial Hospital, Linkou, Kwei-San, Taoyuan 33305, Taiwan
6
Research Center for Food and Cosmetic Safety, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33305, Taiwan
7
Department of Materials Engineering, Ming Chi University of Technology, Tai-Shan, New Taipei City 24301, Taiwan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Academic Editor: Clare Hoskins
Cancers 2021, 13(15), 3690; https://doi.org/10.3390/cancers13153690
Received: 21 May 2021
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Revised: 19 July 2021
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Accepted: 19 July 2021
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Published: 22 July 2021
(This article belongs to the Collection Cancer Nanomedicine)
Simple Summary
To improve the use of hydrophobic photosensitizer IR-780 in photothermal/photodynamic therapy (PTT/PDT), we entrap IR-780 within the lipid bilayer of liposomes (ILs). Compared to free IR-780, ILs showed well-preserved photothermal response by maintaining the photostability of IR-780 from repeated near infrared (NIR) laser exposure both in vitro and in vivo. Combined with fast endocytosis by human glioblastoma cells, ILs demonstrated enhanced cytotoxicity and induced higher cell apoptosis rate toward human glioblastoma cells over free IR-780, due to PTT with overexpression of heat shock protein and PDT with generation of intracellular reactive oxygen species. To overcome the blood–brain barrier, we used convection enhanced delivery (CED) for specific delivery of ILs to brain tumors in intracranial glioma xenograft. Upon three successive NIR laser irradiations, the liposomal IR-780 could significantly improve the anti-cancer efficacy in glioma treatment, leading to diminished intracranial tumor size and prolonged animal survival time.
As a hydrophobic photosensitizer, IR-780 suffers from poor water solubility and low photostability under near infrared (NIR) light, which severely limits its use during successive NIR laser-assisted photothermal/photodynamic therapy (PTT/PDT). To solve this problem, we fabricate cationic IR-780-loaded liposomes (ILs) by entrapping IR-780 within the lipid bilayer of liposomes. We demonstrate enhanced photostability of IR-780 in ILs with well-preserved photothermal response after three repeated NIR laser exposures, in contrast to the rapid decomposition of free IR-780. The cationic nature of ILs promotes fast endocytosis of liposomal IR-780 by U87MG human glioblastoma cells within 30 min. For PTT/PDT in vitro, ILs treatment plus NIR laser irradiation leads to overexpression of heat shock protein 70 and generation of intracellular reactive oxygen species by U87MG cells, resulting in enhanced cytotoxicity and higher cell apoptosis rate. Using intracranial glioma xenograft in nude mice and administration of ILs by convection enhanced delivery (CED) to overcome blood-brain barrier, liposomal IR-780 could be specifically delivered to the brain tumor, as demonstrated from fluorescence imaging. By providing a highly stable liposomal IR-780, ILs significantly improved anti-cancer efficacy in glioma treatment, as revealed from various diagnostic imaging tools and histological examination. Overall, CED of ILs plus successive laser-assisted PTT/PDT may be an alternative approach for treating brain tumor, which can retard glioma growth and prolong animal survival times from orthotopic brain tumor models.
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Keywords:
nanomedicine; cancer therapy; brain tumor; photothermal therapy; photodynamic therapy; liposome; IR-780; convection enhanced delivery
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MDPI and ACS Style
Lu, Y.-J.; S., A.T.; Chuang, C.-C.; Chen, J.-P. Liposomal IR-780 as a Highly Stable Nanotheranostic Agent for Improved Photothermal/Photodynamic Therapy of Brain Tumors by Convection-Enhanced Delivery. Cancers 2021, 13, 3690. https://doi.org/10.3390/cancers13153690
AMA Style
Lu Y-J, S. AT, Chuang C-C, Chen J-P. Liposomal IR-780 as a Highly Stable Nanotheranostic Agent for Improved Photothermal/Photodynamic Therapy of Brain Tumors by Convection-Enhanced Delivery. Cancers. 2021; 13(15):3690. https://doi.org/10.3390/cancers13153690
Chicago/Turabian StyleLu, Yu-Jen, Anilkumar T. S., Chi-Cheng Chuang, and Jyh-Ping Chen. 2021. "Liposomal IR-780 as a Highly Stable Nanotheranostic Agent for Improved Photothermal/Photodynamic Therapy of Brain Tumors by Convection-Enhanced Delivery" Cancers 13, no. 15: 3690. https://doi.org/10.3390/cancers13153690
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