Damaging Tumor Vessels with an Ultrasound-Triggered NO Release Nanosystem to Enhance Drug Accumulation and T Cells Infiltration
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 ChinaCorrespondence: Xueming Li; Hao RenNanjing Tech University, School of Pharmaceutical Science and Pharmaceutical Engineer...
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Dove Medical Press
2021
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oai:doaj.org-article:bf54926a13a7486ca7a2622ecdb3c27d2021-12-02T16:57:44ZDamaging Tumor Vessels with an Ultrasound-Triggered NO Release Nanosystem to Enhance Drug Accumulation and T Cells Infiltration1178-2013https://doaj.org/article/bf54926a13a7486ca7a2622ecdb3c27d2021-04-01T00:00:00Zhttps://www.dovepress.com/damaging-tumor-vessels-with-an-ultrasound-triggered-no-release-nanosys-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yan Xu, Jiwei Liu, Zhangya Liu, Guoguang Chen, Xueming Li, Hao Ren School of Pharmaceutical Science, Nanjing Tech University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Xueming Li; Hao RenNanjing Tech University, School of Pharmaceutical Science and Pharmaceutical Engineering, No. 30 Puzhu South Road, Nanjing, 211816, ChinaEmail Xuemingli@njtech.edu.cn; Hren@njtech.edu.cnIntroduction: 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 plateletsXu YLiu JLiu ZChen GLi XRen HDove Medical Pressarticleintratumoural t cell infiltrationnanoparticles accumulationtumor vascular barriersnitric oxidetumor-associated plateletsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 2597-2613 (2021) |
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intratumoural t cell infiltration nanoparticles accumulation tumor vascular barriers nitric oxide tumor-associated platelets Medicine (General) R5-920 |
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intratumoural t cell infiltration nanoparticles accumulation tumor vascular barriers nitric oxide tumor-associated platelets Medicine (General) R5-920 Xu Y Liu J Liu Z Chen G Li X Ren H Damaging Tumor Vessels with an Ultrasound-Triggered NO Release Nanosystem to Enhance Drug Accumulation and T Cells Infiltration |
| description |
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 ChinaCorrespondence: Xueming Li; Hao RenNanjing Tech University, School of Pharmaceutical Science and Pharmaceutical Engineering, No. 30 Puzhu South Road, Nanjing, 211816, ChinaEmail Xuemingli@njtech.edu.cn; Hren@njtech.edu.cnIntroduction: 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 |
| format |
article |
| author |
Xu Y Liu J Liu Z Chen G Li X Ren H |
| author_facet |
Xu Y Liu J Liu Z Chen G Li X Ren H |
| author_sort |
Xu Y |
| title |
Damaging Tumor Vessels with an Ultrasound-Triggered NO Release Nanosystem to Enhance Drug Accumulation and T Cells Infiltration |
| title_short |
Damaging Tumor Vessels with an Ultrasound-Triggered NO Release Nanosystem to Enhance Drug Accumulation and T Cells Infiltration |
| title_full |
Damaging Tumor Vessels with an Ultrasound-Triggered NO Release Nanosystem to Enhance Drug Accumulation and T Cells Infiltration |
| title_fullStr |
Damaging Tumor Vessels with an Ultrasound-Triggered NO Release Nanosystem to Enhance Drug Accumulation and T Cells Infiltration |
| title_full_unstemmed |
Damaging Tumor Vessels with an Ultrasound-Triggered NO Release Nanosystem to Enhance Drug Accumulation and T Cells Infiltration |
| title_sort |
damaging tumor vessels with an ultrasound-triggered no release nanosystem to enhance drug accumulation and t cells infiltration |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/bf54926a13a7486ca7a2622ecdb3c27d |
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