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Cabozantinib-Loaded PLGA Nanoparticles: A Potential Adjuvant Strategy for Surgically Resected High-Risk Non-Metastatic Renal Cell Carcinoma
DC Field | Value | Language |
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dc.contributor.author | Lee, Hye Won | - |
dc.contributor.author | Seo, Hee Seung | - |
dc.contributor.author | Yeom, Seon-Yong | - |
dc.contributor.author | Kim, Se-Na | - |
dc.contributor.author | Kim, Cho Rim | - |
dc.contributor.author | Park, Dae-Hwan | - |
dc.contributor.author | Park, Wooram | - |
dc.contributor.author | Choy, Young Bin | - |
dc.contributor.author | Park, Chun Gwon | - |
dc.contributor.author | Seo, Seong Il | - |
dc.date.accessioned | 2023-01-09T00:25:08Z | - |
dc.date.available | 2023-01-09T00:25:08Z | - |
dc.date.created | 2022-11-22 | - |
dc.date.issued | 2022-10 | - |
dc.identifier.citation | International Journal of Molecular Sciences, Vol.23 No.20, p. 12634 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | https://hdl.handle.net/10371/188902 | - |
dc.description.abstract | Patients with high-risk non-metastatic renal cell carcinoma (RCC) are at risk of metastatic relapse following nephrectomy. Cabozantinib (CZ), a potent multitarget tyrosine kinase inhibitor, interferes with angiogenesis and immunosuppression associated with surgery-induced metastasis. Here, we explored the therapeutic potential of CZ-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CZ-PLGA-NPs) as an adjuvant strategy for targeting post-nephrectomy metastasis. A clinically relevant subline recapitulating post-nephrectomy lung metastasis of high-risk human RCC, namely Renca-SRLu5-Luc, was established through in vivo serial selection of luciferase-expressing murine RCC Renca-Luc cells. CZ was encapsulated into PLGA-NPs via the conventional single emulsion technique. The multifaceted preclinical antimetastatic efficacy of CZ-PLGA-NPs was assessed in Renca-SRLu5-Luc cells. CZ-PLGA-NPs with a smooth surface displayed desirable physicochemical properties, good CZ encapsulation efficiency, as well as controlled and sustained CZ release. CZ-PLGA-NPs exhibited remarkable dose-dependent toxicity against Renca-SRLu5-Luc cells by inducing G2/M cell cycle arrest and apoptosis. CZ-PLGA-NPs attenuated in vitro colony formation, migration, and invasion by abrogating AKT and ERK1/2 activation. An intravenous injection of CZ-PLGA-NPs markedly reduced lung metastatic burden and prolonged lifespan with favorable safety in the Renca-SRLu5-Luc experimental lung metastasis model. The novel CZ-PLGA-NPs system with multifaceted antimetastatic effects and alleviating off-target toxicity potential is a promising adjunctive agent for patients with surgically resected high-risk RCC. | - |
dc.language | 영어 | - |
dc.publisher | Multidisciplinary Digital Publishing Institute (MDPI) | - |
dc.title | Cabozantinib-Loaded PLGA Nanoparticles: A Potential Adjuvant Strategy for Surgically Resected High-Risk Non-Metastatic Renal Cell Carcinoma | - |
dc.type | Article | - |
dc.identifier.doi | 10.3390/ijms232012634 | - |
dc.citation.journaltitle | International Journal of Molecular Sciences | - |
dc.identifier.wosid | 000874303100001 | - |
dc.identifier.scopusid | 2-s2.0-85140816163 | - |
dc.citation.number | 20 | - |
dc.citation.startpage | 12634 | - |
dc.citation.volume | 23 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Choy, Young Bin | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
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