| Autor: |
Chen Y; Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China., Li ZH; Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China., Pan P; Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China., Zeng RY; Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China., Zhang XZ; Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China. |
| Jazyk: |
angličtina |
| Zdroj: |
ACS nano [ACS Nano] 2021 Jul 27; Vol. 15 (7), pp. 11514-11525. Date of Electronic Publication: 2021 Jul 18. |
| DOI: |
10.1021/acsnano.1c01312 |
| Abstrakt: |
Multiple biological barriers in solid tumors severely restrict the penetration of nanomedicines, which is a main cause for therapeutic failure in traditional tumor treatment. Here, a tumor-specific nanogenerator of peroxynitrite (ONOO - ), prepared by loading cisplatin and sodium nitroprusside into poly(d,l-lactide- co -glycolide) polymersomes, was designed to improve drug delivery and enhance tumor chemotherapy. After a cascade of nicotinamide adenine dinucleotide phosphate oxidases catalysis and glutathione reduction, the nanogenerator, namely, PMCS, could selectively induce the generation of ONOO - in tumor. The generated ONOO - could not only strengthen vascular permeability significantly but also improve the accumulation and penetration of PMCS in tumor by activating matrix metalloproteinases-mediated degradation of extracellular matrix. Along with endocytosis, PMCS released cisplatin to induce tumor cell apoptosis. Moreover, free cisplatin liberated from dead cells infected neighboring tumor cells quickly via ONOO - -mediated up-regulated copper transporter 1, further amplifying chemotherapeutic efficacy. This study advances ONOO - as a potent modality to address the main issues of therapeutic delivery, including but not limited to chemotherapy. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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