细胞外基质
热疗
内化
纳米颗粒
肿瘤微环境
氧化铁纳米粒子
材料科学
生物物理学
细胞外
磁热疗
基质
磁性纳米粒子
纳米技术
纳米医学
癌症研究
渗透(战争)
化学
细胞
肿瘤细胞
免疫学
医学
生物
生物化学
工程类
内科学
免疫组织化学
运筹学
作者
Jelena Kolosnjaj‐Tabi,Riccardo Di Corato,Lénaïc Lartigue,Iris Marangon,Pablo Guardia,Amanda Silva,Nathalie Luciani,Olivier Clémеnt,Patrice Flaud,Jaykrishna Singh,Paolo Decuzzi,Teresa Pellegrino,Claire Wilhelm,Florence Gazeau
出处
期刊:ACS Nano
[American Chemical Society]
日期:2014-04-21
卷期号:8 (5): 4268-4283
被引量:194
摘要
Several studies propose nanoparticles for tumor treatment, yet little is known about the fate of nanoparticles and intimate interactions with the heterogeneous and ever-evolving tumor environment. The latter, rich in extracellular matrix, is responsible for poor penetration of therapeutics and represents a paramount issue in cancer therapy. Hence new strategies start aiming to modulate the neoplastic stroma. From this perspective, we assessed the efficacy of 19 nm PEG-coated iron oxide nanocubes with optimized magnetic properties to mediate mild tumor magnetic hyperthermia treatment. After injection of a low dose of nanocubes (700 μg of iron) into epidermoid carcinoma xenografts in mice, we monitored the effect of heating nanocubes on tumor environment. In comparison with the long-term fate after intravenous administration, we investigated spatiotemporal patterns of nanocube distribution, evaluated the evolution of cubes magnetic properties, and examined nanoparticle clearance and degradation processes. While inside tumors nanocubes retained their magnetic properties and heating capacity throughout the treatment due to a mainly interstitial extracellular location, the particles became inefficient heaters after cell internalization and transfer to spleen and liver. Our multiscale analysis reveals that collagen-rich tumor extracellular matrix confines the majority of nanocubes. However, nanocube-mediated hyperthermia has the potential to “destructure” this matrix and improve nanoparticle and drug penetration into neoplastic tissue. This study provides insight into dynamic interactions between nanoparticles and tumor components under physical stimulation and suggests that nanoparticle-mediated hyperthermia could be used to locally modify tumor stroma and thus improve drug penetration.
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