Integrin receptor-targeted, doxorubicin-loaded cerium oxide nanoparticles delivery to combat glioblastoma.

IF 3.9 Nanomedicine (London, England) Pub Date : 2024-06-20 Epub Date: 2024-06-24 DOI:10.1080/17435889.2024.2350357
Gayathri Koula, Venu Yakati, Hari Krishnareddy Rachamalla, Keerti Bhamidipati, Muralidharan Kathirvel, Rajkumar Banerjee, Nagaprasad Puvvada
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Abstract

Aim: To assess the chemo-immunomodulatory effects of doxorubicin-loaded cerium oxide nanoparticles coated with oleyl amine-linked cyclic RGDfK peptide (CeNP+Dox+RGD) to target both gliomas and its tumor microenvironment (TME) via integrin receptors. Materials & methods: CeNP+Dox+RGD nanoparticles are synthesized by the sequential addition of cerium III chloride heptahydrate, beta-cyclodextrin, oleic acid, and F127 micelle (CeNP). Doxorubicin was then loaded into CeNPs and coated with oleyl amine-linked cyclic RGDfK peptide to form stable CeNP+Dox+RGD nanoparticles. Results: CeNP+Dox+RGD nanoparticles crossed blood-brain barrier (BBB) effectively and demonstrated threefold enhanced survivability in glioma-bearing mice. The IHC profiling of glial tumor cross-sections showed increased CD80 expression (M1 TAMs) and decreased arginase-1 expression (M2 TAMs). Conclusion: CeNP+Dox+RGD can be an immunotherapeutic treatment option to combat glioblastoma.

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以整合素受体为靶向、负载多柔比星的氧化铈纳米颗粒用于抗击胶质母细胞瘤。
目的:评估氧化铈纳米粒子包覆油胺环RGDfK肽(CeNP+Dox+RGD)通过整合素受体靶向胶质瘤及其肿瘤微环境(TME)的化学免疫调节作用。材料与方法CeNP+Dox+RGD纳米粒子由七水氯化铈III、β-环糊精、油酸和F127胶束(CeNP)依次加入合成。然后将多柔比星负载到 CeNPs 中,并包覆上油酸胺连接的环状 RGDfK 肽,形成稳定的 CeNP+Dox+RGD 纳米粒子。结果CeNP+Dox+RGD纳米颗粒能有效穿过血脑屏障(BBB),在胶质瘤小鼠中的存活率提高了三倍。胶质瘤横截面的 IHC 图谱显示,CD80 表达增加(M1 TAMs),精氨酸酶-1 表达减少(M2 TAMs)。结论CeNP+Dox+RGD可作为抗击胶质母细胞瘤的免疫治疗方案。
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