In Vitro and In Vivo Evaluation of a Cyclic LyP-1-Modified Nanosystem for Targeted Endostatin Delivery in a KYSE-30 Cell Xenograft Athymic Nude Mice Model
This work investigated the use of LyP-1 as a homing peptide for p32 receptor targeting on the surface of an endostatin (ENT)-loaded chitosan-grafted nanosystem intended for intracellular delivery of ENT and mitochondrial targeting in a squamous cell carcinoma (SCC) cell line (KYSE-30) model. The ang...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/3/353 |
| _version_ | 1797443675168440320 |
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| author | Samson A. Adeyemi Yahya E. Choonara |
| author_facet | Samson A. Adeyemi Yahya E. Choonara |
| author_sort | Samson A. Adeyemi |
| collection | DOAJ |
| description | This work investigated the use of LyP-1 as a homing peptide for p32 receptor targeting on the surface of an endostatin (ENT)-loaded chitosan-grafted nanosystem intended for intracellular delivery of ENT and mitochondrial targeting in a squamous cell carcinoma (SCC) cell line (KYSE-30) model. The angiogenic factors for VEGF-C and MMP2 were assessed with in vivo evaluation of the nanosystem upon ENT release and tumor necrosis in nude mice with a KYSE-30 cell xenograft. The LyP-1-modified nanosystem revealed a three-fold decrease in proliferation at 1000 µg/mL compared with the control and facilitated receptor-mediated cellular uptake and internalization. In addition, targeting of the Lyp-1-functionalized nanosystem to mitochondrial and nuclear proteins in vitro and in vivo was achieved. Up to 60% inhibition of KYSE-30 cell migration was observed and the expressions of VEGF-C and MMP-2 as angiogenic markers were reduced 3- and 2-fold, respectively. A marked reduction in tumor mass was recorded (43.25%) with the control, a 41.36% decrease with the nanoparticles and a 61.01% reduction with the LyP-1-modified nanosystem following treatment in mice. The LyP-1-functionalized nanosystem targeted tumor lymphatics, instigated nuclear rupture and mitochondrial distortion, and decreased cell proliferation and migration with inhibition of VEGF-C and MMP2 expression. |
| first_indexed | 2024-03-09T13:00:28Z |
| format | Article |
| id | doaj.art-1a227d242800401799634ea2ecc3aafd |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T13:00:28Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-1a227d242800401799634ea2ecc3aafd2023-11-30T21:54:55ZengMDPI AGPharmaceuticals1424-82472022-03-0115335310.3390/ph15030353In Vitro and In Vivo Evaluation of a Cyclic LyP-1-Modified Nanosystem for Targeted Endostatin Delivery in a KYSE-30 Cell Xenograft Athymic Nude Mice ModelSamson A. Adeyemi0Yahya E. Choonara1Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South AfricaWits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South AfricaThis work investigated the use of LyP-1 as a homing peptide for p32 receptor targeting on the surface of an endostatin (ENT)-loaded chitosan-grafted nanosystem intended for intracellular delivery of ENT and mitochondrial targeting in a squamous cell carcinoma (SCC) cell line (KYSE-30) model. The angiogenic factors for VEGF-C and MMP2 were assessed with in vivo evaluation of the nanosystem upon ENT release and tumor necrosis in nude mice with a KYSE-30 cell xenograft. The LyP-1-modified nanosystem revealed a three-fold decrease in proliferation at 1000 µg/mL compared with the control and facilitated receptor-mediated cellular uptake and internalization. In addition, targeting of the Lyp-1-functionalized nanosystem to mitochondrial and nuclear proteins in vitro and in vivo was achieved. Up to 60% inhibition of KYSE-30 cell migration was observed and the expressions of VEGF-C and MMP-2 as angiogenic markers were reduced 3- and 2-fold, respectively. A marked reduction in tumor mass was recorded (43.25%) with the control, a 41.36% decrease with the nanoparticles and a 61.01% reduction with the LyP-1-modified nanosystem following treatment in mice. The LyP-1-functionalized nanosystem targeted tumor lymphatics, instigated nuclear rupture and mitochondrial distortion, and decreased cell proliferation and migration with inhibition of VEGF-C and MMP2 expression.https://www.mdpi.com/1424-8247/15/3/353targeted drug deliveryLyP-1 homing peptideendostatinnanoparticlesanti-angiogenicnecrosis |
| spellingShingle | Samson A. Adeyemi Yahya E. Choonara In Vitro and In Vivo Evaluation of a Cyclic LyP-1-Modified Nanosystem for Targeted Endostatin Delivery in a KYSE-30 Cell Xenograft Athymic Nude Mice Model Pharmaceuticals targeted drug delivery LyP-1 homing peptide endostatin nanoparticles anti-angiogenic necrosis |
| title | In Vitro and In Vivo Evaluation of a Cyclic LyP-1-Modified Nanosystem for Targeted Endostatin Delivery in a KYSE-30 Cell Xenograft Athymic Nude Mice Model |
| title_full | In Vitro and In Vivo Evaluation of a Cyclic LyP-1-Modified Nanosystem for Targeted Endostatin Delivery in a KYSE-30 Cell Xenograft Athymic Nude Mice Model |
| title_fullStr | In Vitro and In Vivo Evaluation of a Cyclic LyP-1-Modified Nanosystem for Targeted Endostatin Delivery in a KYSE-30 Cell Xenograft Athymic Nude Mice Model |
| title_full_unstemmed | In Vitro and In Vivo Evaluation of a Cyclic LyP-1-Modified Nanosystem for Targeted Endostatin Delivery in a KYSE-30 Cell Xenograft Athymic Nude Mice Model |
| title_short | In Vitro and In Vivo Evaluation of a Cyclic LyP-1-Modified Nanosystem for Targeted Endostatin Delivery in a KYSE-30 Cell Xenograft Athymic Nude Mice Model |
| title_sort | in vitro and in vivo evaluation of a cyclic lyp 1 modified nanosystem for targeted endostatin delivery in a kyse 30 cell xenograft athymic nude mice model |
| topic | targeted drug delivery LyP-1 homing peptide endostatin nanoparticles anti-angiogenic necrosis |
| url | https://www.mdpi.com/1424-8247/15/3/353 |
| work_keys_str_mv | AT samsonaadeyemi invitroandinvivoevaluationofacycliclyp1modifiednanosystemfortargetedendostatindeliveryinakyse30cellxenograftathymicnudemicemodel AT yahyaechoonara invitroandinvivoevaluationofacycliclyp1modifiednanosystemfortargetedendostatindeliveryinakyse30cellxenograftathymicnudemicemodel |