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In Vivo Evaluation of Multifunctional Gold Nanorods for Boron Neutron Capture and Photothermal Therapies
ACS Applied Materials & Interfaces ( IF 9.5 ) Pub Date : 2021-10-13 , DOI: 10.1021/acsami.0c17575
Krishna R Pulagam 1 , Malou Henriksen-Lacey 1, 2 , Kepa B Uribe 1 , Carlos Renero-Lecuna 1 , Jatish Kumar 3 , Alexandra Charalampopoulou 4 , Angelica Facoetti 4 , Nicoletta Protti 5, 6 , Vanessa Gómez-Vallejo 1 , Zuriñe Baz 1 , Vished Kumar 1 , Ana Sánchez-Iglesias 1, 2 , Saverio Altieri 5, 6 , Unai Cossío 1 , Desire Di Silvio 1 , Angel M Martínez-Villacorta 1 , Ane Ruiz de Angulo 7 , Luka Rejc 1, 8 , Luis M Liz-Marzán 1, 2, 9 , Jordi Llop 1, 10
Affiliation  

The incidence and mortality of cancer demand more innovative approaches and combination therapies to increase treatment efficacy and decrease off-target side effects. We describe a boron-rich nanoparticle composite with potential applications in both boron neutron capture therapy (BNCT) and photothermal therapy (PTT). Our strategy is based on gold nanorods (AuNRs) stabilized with polyethylene glycol and functionalized with the water-soluble complex cobalt bis(dicarbollide) ([3,3′-Co(1,2-C2B9H11)2]), commonly known as COSAN. Radiolabeling with the positron emitter copper-64 (64Cu) enabled in vivo tracking using positron emission tomography imaging. 64Cu-labeled multifunctionalized AuNRs proved to be radiochemically stable and capable of being accumulated in the tumor after intravenous administration in a mouse xenograft model of gastrointestinal cancer. The resulting multifunctional AuNRs showed high biocompatibility and the capacity to induce local heating under external stimulation and trigger cell death in heterogeneous cancer spheroids as well as the capacity to decrease cell viability under neutron irradiation in cancer cells. These results position our nanoconjugates as suitable candidates for combined BNCT/PTT therapies.

中文翻译:

用于硼中子捕获和光热疗法的多功能金纳米棒的体内评估

癌症的发病率和死亡率需要更多创新的方法和联合疗法来提高治疗效果并减少脱靶副作用。我们描述了一种在硼中子俘获疗法 (BNCT) 和光热疗法 (PTT) 中具有潜在应用的富硼纳米颗粒复合材料。我们的策略是基于用聚乙二醇稳定的金纳米棒 (AuNRs),并用水溶性复合钴(dicarbollide) ([3,3'-Co(1,2-C 2 B 9 H 11 ) 2 ] - ),俗称COSAN。体内启用正电子发射体铜 64 ( 64 Cu)的放射性标记使用正电子发射断层扫描成像进行跟踪。在胃肠癌小鼠异种移植模型中静脉给药后, 64种 Cu 标记的多功能 AuNR 被证明具有放射化学稳定性,并且能够在肿瘤中积累。由此产生的多功能AuNRs显示出高生物相容性和在外部刺激下诱导局部加热并在异质癌症球体中引发细胞死亡的能力,以及在癌细胞中的中子照射下降低细胞活力的能力。这些结果将我们的纳米偶联物定位为联合 BNCT/PTT 疗法的合适候选者。
更新日期:2021-10-27
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