دورية أكاديمية
Targeting vascular disrupting agent-treated tumor microenvironment with tissue-penetrating nanotherapy
| العنوان: | Targeting vascular disrupting agent-treated tumor microenvironment with tissue-penetrating nanotherapy |
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| المؤلفون: | Valeria Sidorenko, Pablo Scodeller, Ain Uustare, Ivan Ogibalov, Andrus Tasa, Olga Tshubrik, Liis Salumäe, Kazuki N. Sugahara, Lorena Simón-Gracia, Tambet Teesalu |
| المصدر: | Scientific Reports, Vol 14, Iss 1, Pp 1-16 (2024) |
| بيانات النشر: | Nature Portfolio, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Vascular disrupting agent, CA4P, Utorubicin, Tumor-penetrating peptide, iRGD, Polymersomes, Medicine, Science |
| الوصف: | Abstract Cancer treatment with vascular disrupting agents (VDAs) causes rapid and extensive necrosis in solid tumors. However, these agents fall short in eliminating all malignant cells, ultimately leading to tumor regrowth. Here, we investigated whether the molecular changes in the tumor microenvironment induced by VDA treatment sensitize the tumors for secondary nanotherapy enhanced by clinical-stage tumor penetrating peptide iRGD. Treatment of peritoneal carcinomatosis (PC) and breast cancer mice with VDA combretastatin A-4 phosphate (CA4P) resulted in upregulation of the iRGD receptors αv-integrins and NRP-1, particularly in the peripheral tumor tissue. In PC mice treated with CA4P, coadministration of iRGD resulted in an approximately threefold increase in tumor accumulation and a more homogenous distribution of intraperitoneally administered nanoparticles. Notably, treatment with a combination of CA4P, iRGD, and polymersomes loaded with a novel anthracycline Utorubicin (UTO-PS) resulted in a significant decrease in the overall tumor burden in PC-bearing mice, while avoiding overt toxicities. Our results indicate that VDA-treated tumors can be targeted therapeutically using iRGD-potentiated nanotherapy and warrant further studies on the sequential targeting of VDA-induced molecular signatures. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-024-64610-7 |
| URL الوصول: | https://doaj.org/article/c2c0fe2679b5496d819101b030d83b28 |
| رقم الأكسشن: | edsdoj.2c0fe2679b5496d819101b030d83b28 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-024-64610-7 |