Inhibition of Endothelial Cell Tube Formation by Anti-Vascular Endothelial Growth Factor/Anti-Angiopoietin-2 RNA Nanoparticles
RNA nanoparticles, derived from the packaging RNA three-way junction motif (pRNA-3WJ) of the bacteriophage phi29 DNA packaging motor, have been demonstrated to be thermodynamically and chemically stable, with promise as a nanodelivery system. <b>Background/Objectives</b>: A previous stud...
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2025-01-01
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| author | Cheng Zhong Zhanquan Shi Chia-Yang Liu Daniel W. Binzel Kai Jin Xin Li Peixuan Guo S. Kevin Li |
| author_facet | Cheng Zhong Zhanquan Shi Chia-Yang Liu Daniel W. Binzel Kai Jin Xin Li Peixuan Guo S. Kevin Li |
| author_sort | Cheng Zhong |
| collection | DOAJ |
| description | RNA nanoparticles, derived from the packaging RNA three-way junction motif (pRNA-3WJ) of the bacteriophage phi29 DNA packaging motor, have been demonstrated to be thermodynamically and chemically stable, with promise as a nanodelivery system. <b>Background/Objectives</b>: A previous study showed that RNA nanoparticles with antiangiogenic aptamers (anti-vascular endothelial growth factor (VEGF) and anti-angiopoietin-2 (Ang2) aptamers) inhibited cell proliferation via WST-1 assay. To further investigate the antiangiogenic potential of these RNA nanoparticles, a modified three-dimensional (3D) spheroid sprouting assay model of human umbilical vein endothelial cells was utilized in the present study. <b>Methods</b>: Three groups of RNA nanoparticles were evaluated, namely, pRNA-3WJ series, RNA square series (polygon-type RNA nanoparticles), and 8WJ series (multiple-way junction RNA nanoparticles), which were conjugated with a single anti-VEGF, the combination of one anti-VEGF and one anti-Ang2, or multiple anti-VEGF aptamers. The core scaffold RNA nanoparticles (without aptamers) were used as the references, and bevacizumab was used as the positive control. <b>Results</b>: The results demonstrated the inhibition effects of the RNA nanoparticles on endothelial cell tube formation at 67 nM in a 3D spheroid sprouting model. The results in the 3D spheroid sprouting assay are consistent with those of the WST-1 proliferation assays. <b>Conclusions</b>: Among the RNA nanoparticles evaluated, 3WJ-3VEGF and SQR-VEGF-Ang2 had inhibition effects equivalent to bevacizumab and were promising for anti-angiogenesis treatment. |
| format | Article |
| id | doaj-art-0a11f72fb37d4705b0ac98dab16a26fa |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Pharmaceutics |
| spelling | doaj-art-0a11f72fb37d4705b0ac98dab16a26fa2025-01-24T13:45:44ZengMDPI AGPharmaceutics1999-49232025-01-011715510.3390/pharmaceutics17010055Inhibition of Endothelial Cell Tube Formation by Anti-Vascular Endothelial Growth Factor/Anti-Angiopoietin-2 RNA NanoparticlesCheng Zhong0Zhanquan Shi1Chia-Yang Liu2Daniel W. Binzel3Kai Jin4Xin Li5Peixuan Guo6S. Kevin Li7Division of Pharmaceutical Sciences, James L Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USADivision of Pharmaceutical Sciences, James L Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USADepartment of Ophthalmology, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USACenter for RNA Nanobiotechnology and Nanomedicine, College of Pharmacy, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USACenter for RNA Nanobiotechnology and Nanomedicine, College of Pharmacy, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USACenter for RNA Nanobiotechnology and Nanomedicine, College of Pharmacy, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USACenter for RNA Nanobiotechnology and Nanomedicine, College of Pharmacy, James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USADivision of Pharmaceutical Sciences, James L Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USARNA nanoparticles, derived from the packaging RNA three-way junction motif (pRNA-3WJ) of the bacteriophage phi29 DNA packaging motor, have been demonstrated to be thermodynamically and chemically stable, with promise as a nanodelivery system. <b>Background/Objectives</b>: A previous study showed that RNA nanoparticles with antiangiogenic aptamers (anti-vascular endothelial growth factor (VEGF) and anti-angiopoietin-2 (Ang2) aptamers) inhibited cell proliferation via WST-1 assay. To further investigate the antiangiogenic potential of these RNA nanoparticles, a modified three-dimensional (3D) spheroid sprouting assay model of human umbilical vein endothelial cells was utilized in the present study. <b>Methods</b>: Three groups of RNA nanoparticles were evaluated, namely, pRNA-3WJ series, RNA square series (polygon-type RNA nanoparticles), and 8WJ series (multiple-way junction RNA nanoparticles), which were conjugated with a single anti-VEGF, the combination of one anti-VEGF and one anti-Ang2, or multiple anti-VEGF aptamers. The core scaffold RNA nanoparticles (without aptamers) were used as the references, and bevacizumab was used as the positive control. <b>Results</b>: The results demonstrated the inhibition effects of the RNA nanoparticles on endothelial cell tube formation at 67 nM in a 3D spheroid sprouting model. The results in the 3D spheroid sprouting assay are consistent with those of the WST-1 proliferation assays. <b>Conclusions</b>: Among the RNA nanoparticles evaluated, 3WJ-3VEGF and SQR-VEGF-Ang2 had inhibition effects equivalent to bevacizumab and were promising for anti-angiogenesis treatment.https://www.mdpi.com/1999-4923/17/1/55nanotechnologyRNA nanoparticleanti-angiogenesis3D spheroid sprouting assay |
| spellingShingle | Cheng Zhong Zhanquan Shi Chia-Yang Liu Daniel W. Binzel Kai Jin Xin Li Peixuan Guo S. Kevin Li Inhibition of Endothelial Cell Tube Formation by Anti-Vascular Endothelial Growth Factor/Anti-Angiopoietin-2 RNA Nanoparticles Pharmaceutics nanotechnology RNA nanoparticle anti-angiogenesis 3D spheroid sprouting assay |
| title | Inhibition of Endothelial Cell Tube Formation by Anti-Vascular Endothelial Growth Factor/Anti-Angiopoietin-2 RNA Nanoparticles |
| title_full | Inhibition of Endothelial Cell Tube Formation by Anti-Vascular Endothelial Growth Factor/Anti-Angiopoietin-2 RNA Nanoparticles |
| title_fullStr | Inhibition of Endothelial Cell Tube Formation by Anti-Vascular Endothelial Growth Factor/Anti-Angiopoietin-2 RNA Nanoparticles |
| title_full_unstemmed | Inhibition of Endothelial Cell Tube Formation by Anti-Vascular Endothelial Growth Factor/Anti-Angiopoietin-2 RNA Nanoparticles |
| title_short | Inhibition of Endothelial Cell Tube Formation by Anti-Vascular Endothelial Growth Factor/Anti-Angiopoietin-2 RNA Nanoparticles |
| title_sort | inhibition of endothelial cell tube formation by anti vascular endothelial growth factor anti angiopoietin 2 rna nanoparticles |
| topic | nanotechnology RNA nanoparticle anti-angiogenesis 3D spheroid sprouting assay |
| url | https://www.mdpi.com/1999-4923/17/1/55 |
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