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Cabozantinib-Loaded PLGA Nanoparticles: A Potential Adjuvant Strategy for Surgically Resected High-Risk Non-Metastatic Renal Cell Carcinoma
- Source :
- International Journal of Molecular Sciences, Vol 23, Iss 20, p 12634 (2022)
- Publication Year :
- 2022
- Publisher :
- MDPI AG, 2022.
-
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.
Details
- Language :
- English
- ISSN :
- 14220067 and 16616596
- Volume :
- 23
- Issue :
- 20
- Database :
- Directory of Open Access Journals
- Journal :
- International Journal of Molecular Sciences
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.7f65aeee7db4e239052b1542e102686
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/ijms232012634