Abstract | 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.
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Authors | Yan Xu, Jiwei Liu, Zhangya Liu, Guoguang Chen, Xueming Li, Hao Ren |
Journal | International journal of nanomedicine
(Int J Nanomedicine)
Vol. 16
Pg. 2597-2613
( 2021)
ISSN: 1178-2013 [Electronic] New Zealand |
PMID | 33833514
(Publication Type: Journal Article)
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Copyright | © 2021 Xu et al. |
Chemical References |
- Antineoplastic Agents, Phytogenic
- Nitroso Compounds
- S-nitrosoalbumin, human
- Nitric Oxide
- Paclitaxel
- Serum Albumin, Human
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Topics |
- Animals
- Antineoplastic Agents, Phytogenic
(administration & dosage, pharmacokinetics, pharmacology)
- Apoptosis
- Breast Neoplasms
(drug therapy, immunology, metabolism, pathology)
- Cell Proliferation
- Female
- Humans
- Lymphocytes, Tumor-Infiltrating
(immunology)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Nanoparticles
(administration & dosage, chemistry)
- Nitric Oxide
(metabolism)
- Nitroso Compounds
(chemistry)
- Paclitaxel
(administration & dosage, pharmacokinetics, pharmacology)
- Serum Albumin, Human
(chemistry)
- Tissue Distribution
- Tumor Cells, Cultured
- Tumor Microenvironment
(drug effects, immunology)
- Ultrasonic Waves
- Xenograft Model Antitumor Assays
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