期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 20, 页码 -出版社
MDPI
DOI: 10.3390/ijms232012634
关键词
adjuvant; cabozantinib; drug delivery; enhanced permeability retention; nanoparticle; poly(lactic-co-glycolic acid); post-surgery metastasis; renal cell carcinoma
资金
- National Research Foundation of Korea - Ministry of Science and ICT [NRF-2019R1A2C1089141, NRF-2019R1C1C1006300, NRF-2022R1A4A2000776]
- Korean Fund for Regenerative Medicine (KFRM) - Korea government (the Ministry of Science and ICT) [KFRM 21A0501L1]
- Korean Fund for Regenerative Medicine (KFRM) - Korea government (Ministry of Health Welfare) [KFRM 21A0501L1]
The use of CZ-loaded PLGA nanoparticles as an adjuvant therapy for post-nephrectomy metastasis shows promising results in inhibiting tumor growth and metastasis in renal cell carcinoma.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据