Tyrosine kinase inhibitor-loaded biomimetic nanoparticles as a treatment for osteosarcoma
Abstract Small-molecule tyrosine kinase inhibitors (TKIs) represent a potentially powerful approach to the treatment of osteosarcoma (OS). However, dose-limiting toxicity, therapeutic efficacy, and targeting specificity are significant barriers to the use of TKIs in the clinic. Notably among TKIs, p...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Cancer Nanotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12645-022-00146-7 |
| _version_ | 1797985584423108608 |
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| author | Federica Giordano Stefania Lenna Gherardo Baudo Riccardo Rampado Matteo Massaro Enrica De Rosa April Ewing Lyazat Kurenbekova Marco Agostini Jason T. Yustein Francesca Taraballi |
| author_facet | Federica Giordano Stefania Lenna Gherardo Baudo Riccardo Rampado Matteo Massaro Enrica De Rosa April Ewing Lyazat Kurenbekova Marco Agostini Jason T. Yustein Francesca Taraballi |
| author_sort | Federica Giordano |
| collection | DOAJ |
| description | Abstract Small-molecule tyrosine kinase inhibitors (TKIs) represent a potentially powerful approach to the treatment of osteosarcoma (OS). However, dose-limiting toxicity, therapeutic efficacy, and targeting specificity are significant barriers to the use of TKIs in the clinic. Notably among TKIs, ponatinib demonstrated potent anti-tumor activity; however, it received an FDA black box warning for potential side effects. We propose ponatinib-loaded biomimetic nanoparticles (NPs) to repurpose ponatinib as an efficient therapeutic option for OS. In this study, we demonstrate enhanced targeting ability and maintain potent ponatinib nano-therapeutic activity, while also reducing toxicity. In in vitro two- and three-dimensional models, we demonstrate that ponatinib-loaded biomimetic NPs maintain the efficacy of the free drug, while in vivo we show that they can improve tumor targeting, slow tumor growth, and reduce evidence of systemic toxicities. Though there is limited Pon encapsulation within NPs, this platform may improve current therapeutic approaches and reduce dosage-related side effects to achieve better clinical outcomes in OS patients. Graphical Abstract |
| first_indexed | 2024-04-11T07:20:27Z |
| format | Article |
| id | doaj.art-e83e63878afd44c580cc56f28baf503d |
| institution | Directory Open Access Journal |
| issn | 1868-6958 1868-6966 |
| language | English |
| last_indexed | 2024-04-11T07:20:27Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Nanotechnology |
| spelling | doaj.art-e83e63878afd44c580cc56f28baf503d2022-12-22T04:37:48ZengBMCCancer Nanotechnology1868-69581868-69662022-12-0113112910.1186/s12645-022-00146-7Tyrosine kinase inhibitor-loaded biomimetic nanoparticles as a treatment for osteosarcomaFederica Giordano0Stefania Lenna1Gherardo Baudo2Riccardo Rampado3Matteo Massaro4Enrica De Rosa5April Ewing6Lyazat Kurenbekova7Marco Agostini8Jason T. Yustein9Francesca Taraballi10Center for Musculoskeletal Regeneration, Houston Methodist Research InstituteCenter for Musculoskeletal Regeneration, Houston Methodist Research InstituteCenter for Musculoskeletal Regeneration, Houston Methodist Research InstituteCenter for Musculoskeletal Regeneration, Houston Methodist Research InstituteCenter for Musculoskeletal Regeneration, Houston Methodist Research InstituteCenter for Musculoskeletal Regeneration, Houston Methodist Research InstituteCenter for Musculoskeletal Regeneration, Houston Methodist Research InstituteTexas Children’s Cancer and Hematology Center, The Faris D. Virani Ewing Sarcoma Center, Baylor College of MedicineNano-Inspired Biomedicine Laboratory, Institute of Pediatric Research—Città della SperanzaTexas Children’s Cancer and Hematology Center, The Faris D. Virani Ewing Sarcoma Center, Baylor College of MedicineCenter for Musculoskeletal Regeneration, Houston Methodist Research InstituteAbstract Small-molecule tyrosine kinase inhibitors (TKIs) represent a potentially powerful approach to the treatment of osteosarcoma (OS). However, dose-limiting toxicity, therapeutic efficacy, and targeting specificity are significant barriers to the use of TKIs in the clinic. Notably among TKIs, ponatinib demonstrated potent anti-tumor activity; however, it received an FDA black box warning for potential side effects. We propose ponatinib-loaded biomimetic nanoparticles (NPs) to repurpose ponatinib as an efficient therapeutic option for OS. In this study, we demonstrate enhanced targeting ability and maintain potent ponatinib nano-therapeutic activity, while also reducing toxicity. In in vitro two- and three-dimensional models, we demonstrate that ponatinib-loaded biomimetic NPs maintain the efficacy of the free drug, while in vivo we show that they can improve tumor targeting, slow tumor growth, and reduce evidence of systemic toxicities. Though there is limited Pon encapsulation within NPs, this platform may improve current therapeutic approaches and reduce dosage-related side effects to achieve better clinical outcomes in OS patients. Graphical Abstracthttps://doi.org/10.1186/s12645-022-00146-7Tyrosine kinase inhibitorPonatinibOsteosarcomaBiomimicryNanoparticleDrug delivery system |
| spellingShingle | Federica Giordano Stefania Lenna Gherardo Baudo Riccardo Rampado Matteo Massaro Enrica De Rosa April Ewing Lyazat Kurenbekova Marco Agostini Jason T. Yustein Francesca Taraballi Tyrosine kinase inhibitor-loaded biomimetic nanoparticles as a treatment for osteosarcoma Cancer Nanotechnology Tyrosine kinase inhibitor Ponatinib Osteosarcoma Biomimicry Nanoparticle Drug delivery system |
| title | Tyrosine kinase inhibitor-loaded biomimetic nanoparticles as a treatment for osteosarcoma |
| title_full | Tyrosine kinase inhibitor-loaded biomimetic nanoparticles as a treatment for osteosarcoma |
| title_fullStr | Tyrosine kinase inhibitor-loaded biomimetic nanoparticles as a treatment for osteosarcoma |
| title_full_unstemmed | Tyrosine kinase inhibitor-loaded biomimetic nanoparticles as a treatment for osteosarcoma |
| title_short | Tyrosine kinase inhibitor-loaded biomimetic nanoparticles as a treatment for osteosarcoma |
| title_sort | tyrosine kinase inhibitor loaded biomimetic nanoparticles as a treatment for osteosarcoma |
| topic | Tyrosine kinase inhibitor Ponatinib Osteosarcoma Biomimicry Nanoparticle Drug delivery system |
| url | https://doi.org/10.1186/s12645-022-00146-7 |
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