Heat-Generating Iron Oxide Nanocubes: Subtle "Destructurators" of the Tumoral Microenvironment
Heat-Generating Iron Oxide Nanocubes: Subtle "Destructurators" of the Tumoral Microenvironment
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DOI：
10.1021/nn405356r
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发表时间：
2014-05-01
期刊：
影响因子：
17.1
通讯作者：
Gazeau, Florence
中科院分区：
文献类型：
--
作者：
Kolosnjaj-Tabi, Jelena;Di Corato, Riccardo;Gazeau, Florence
一些研究提出纳米粒子用于肿瘤治疗，但对纳米粒子的命运以及与异质和不断进化的肿瘤环境的密切相互作用知之甚少。后者富含细胞外基质，是治疗药物渗透性差的原因，是癌症治疗中的一个重要问题。因此，新的策略开始着眼于调节肿瘤间质。从这个角度，我们评估了具有优化磁性的19 nm聚乙二醇包覆的氧化铁纳米立方体在介导轻度肿瘤磁热治疗方面的有效性。在小鼠表皮样癌异种移植瘤中注射低剂量纳米立方体(700毫克铁)后，我们监测了加热纳米立方体对肿瘤环境的影响。与静脉给药后的长期命运相比，我们调查了纳米立方体分布的时空模式，评估了立方体磁性的演变，并检查了纳米颗粒的清除和降解过程。虽然肿瘤内的纳米立方体由于主要位于细胞外间隙而在整个治疗过程中保持了其磁性和加热能力，但在细胞内化并转移到脾和肝脏后，颗粒成为无效的加热器。我们的多尺度分析显示，富含胶原蛋白的肿瘤细胞外基质限制了大部分纳米立方体。然而，纳米立方体介导的热疗有可能“破坏”这种基质，并改善纳米颗粒和药物对肿瘤组织的渗透。这项研究提供了物理刺激下纳米颗粒与肿瘤成分之间的动态相互作用的洞察力，并表明纳米颗粒介导的热疗可以用于局部修饰肿瘤间质，从而提高药物的渗透性。
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 mu g 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.