Damaging Tumor Vessels with an Ultrasound-Triggered NO Release Nanosystem to Enhance Drug Accumulation and T Cells Infiltration
Authors Xu Y, Liu J, Liu Z, Chen G, Li X, Ren H
Received 3 December 2020
Accepted for publication 16 March 2021
Published 1 April 2021 Volume 2021:16 Pages 2597—2613
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Mian Wang
Yan Xu, Jiwei Liu, Zhangya Liu, Guoguang Chen, Xueming Li, Hao Ren
School of Pharmaceutical Science, Nanjing Tech University, Nanjing, Jiangsu, People’s Republic of China
Correspondence: Xueming Li; Hao Ren
Nanjing Tech University, School of Pharmaceutical Science and Pharmaceutical Engineering, No. 30 Puzhu South Road, Nanjing, 211816, China
Email [email protected]; [email protected]
Introduction: Limited by tumor vascular barriers, restricted intratumoural T cell infiltration and nanoparticles accumulation remain major bottlenecks for anticancer therapy. Platelets are now known to maintain tumor vascular integrity. Therefore, inhibition of tumor-associated platelets may be an effective method to increase T cell infiltration and drug accumulation at tumor sites. Herein, we designed an ultrasound-responsive nitric oxide (NO) release nanosystem, SNO-HSA-PTX, which can release NO in response to ultrasound (US) irradiation, thereby inhibiting platelet function and opening the tumor vascular barrier, promoting drug accumulation and T cell infiltration.
Methods: We evaluated the ability of SNO-HSA-PTX to release NO in response to US irradiation. We also tested the effect of SNO-HSA-PTX on platelet function. Plenty of studies including cytotoxicity, pharmacokinetics study, biodistribution, blood perfusion, T cell infiltration, in vivo antitumor efficacy and safety assessment were conducted to investigate the antitumor effect of SNO-HSA-PTX.
Results: SNO-HSA-PTX with US irradiation inhibited tumor-associated platelets activation and induced openings in the tumor vascular barriers, which promoted the accumulation of SNO-HSA-PTX nanoparticles to the tumor sites. Meanwhile, the damaged vascular barriers allowed oxygen-carrying hemoglobin to infiltrate tumor regions, alleviating hypoxia of the tumor microenvironment. In addition, the intratumoral T cell infiltration was augmented, together with chemotherapy and NO therapy, which greatly inhibited tumor growth.
Discussion: Our research designed a simple strategy to open the vascular barrier by inhibiting the tumor-associated platelets, which provide new ideas for anti-tumor treatment.
Keywords: intratumoural T cell infiltration, nanoparticles accumulation, tumor vascular barriers, nitric oxide, tumor-associated platelets
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]