Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27013, USA.
Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294, USA.
Biomaterials. 2018 Nov;182:114-126. doi: 10.1016/j.biomaterials.2018.08.001. Epub 2018 Aug 4.
At the intersection of the newly emerging fields of optoacoustic imaging and theranostic nanomedicine, promising clinical progress can be made in dismal prognosis of ovarian cancer. An acidic pH targeted wormhole mesoporous silica nanoparticle (V7-RUBY) was developed to serve as a novel tumor specific theranostic nanoparticle detectable using multispectral optoacoustic tomographic (MSOT) imaging. We report the synthesis of a small, < 40 nm, biocompatible asymmetric wormhole pore mesoporous silica core particle that has both large loading capacity and favorable release kinetics combined with tumor-specific targeting and gatekeeping. V7-RUBY exploits the acidic tumor microenvironment for tumor-specific targeting and tumor-specific release. In vitro, treatment with V7-RUBY containing either paclitaxel or carboplatin resulted in increased cell death at pH 6.6 in comparison to drug alone (p < 0.0001). In orthotopic ovarian xenograft mouse models, V7-RUBY containing IR780 was specifically detected within the tumor 7X and 4X higher than the liver and >10X higher than in the kidney using both multispectral optoacoustic tomography (MSOT) imaging with secondary confirmation using near infrared fluorescence imaging (p < 0.0004). The V7-RUBY system carrying a cargo of either contrast agent or an anti-neoplastic drug has the potential to become a theranostic nanoparticle which can improve both diagnosis and treatment of ovarian cancer.
在新兴的光声成像和治疗性纳米医学领域的交叉点,可以在卵巢癌预后不良的情况下取得有希望的临床进展。开发了一种靶向酸性 pH 值的虫孔介孔硅纳米粒子(V7-RUBY),用作新型肿瘤特异性治疗性纳米粒子,可通过多光谱光声断层扫描(MSOT)成像检测。我们报告了一种小的,<40nm,生物相容性的不对称虫孔孔介孔硅核粒子的合成,该粒子具有大的载药能力和有利的释放动力学,结合了肿瘤特异性靶向和门控作用。V7-RUBY 利用酸性肿瘤微环境进行肿瘤特异性靶向和肿瘤特异性释放。在体外,与单独药物相比,用含有紫杉醇或卡铂的 V7-RUBY 处理可导致 pH 6.6 时细胞死亡增加(p<0.0001)。在卵巢原位异种移植小鼠模型中,V7-RUBY 中含有 IR780 的肿瘤内特异性检测比肝脏高 7 倍,比肾脏高 10 倍,使用多光谱光声断层扫描(MSOT)成像进行二次确认,比肾脏高 4 倍(p<0.0004)。携带造影剂或抗肿瘤药物的 V7-RUBY 系统具有成为治疗性纳米粒子的潜力,可改善卵巢癌的诊断和治疗。