Pulsed ultrasound enhances nanoparticle penetration into breast cancer spheroids.

Pulsed ultrasound enhances nanoparticle penetration into breast cancer spheroids.
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DOI:
10.1021/mp100280b
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发表时间:
2010-12-06
影响因子:
4.9
通讯作者:
El-Sayed ME
El-Sayed ME
中科院分区:
医学2区
文献类型:
--
作者:
Grainger SJ;Serna JV;Sunny S;Zhou Y;Deng CX;El-Sayed ME

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实体瘤的有效治疗需要抗癌药物在整个肿瘤体积内均匀分布,以将致死浓度递送至耐药癌细胞和肿瘤起始癌症干细胞。然而,小分子量化疗剂和载药聚合物和脂质颗粒渗透到实体瘤的缺氧和坏死区域仍然是一个重大挑战。本文报道了脉冲超声增强纳米荧光颗粒穿透MCF-7乳腺癌球体(直径300-350 μm)的结果,作为颗粒尺寸和电荷的函数。在存在微泡的情况下应用脉冲超声,与未暴露于超声的那些相比,小(20 nm)颗粒在球状体的核心中实现6-20倍高的渗透和浓度。粒径增加到40 nm和100 nm导致它们分别有效渗透到球状体的核心中9倍和3倍。此外,阴离子羧酸盐颗粒实现了更高的渗透率(2.3、3.7和4.7倍)进入核心在相同的实验条件下,在US暴露30、60和90秒后,与中性颗粒(2.2、1.9和2.4倍)和阳离子颗粒(1.5、1.4和1.9倍)相比,MCF-7乳腺癌球状体的平均粒径为0.25 μ m。这些结果证明了利用脉冲超声来增加纳米尺寸的颗粒渗透到模拟肿瘤组织的MCF-7球状体中的可行性。还说明了颗粒性质对增透效果的影响。
Effective treatment of solid tumors requires homogenous distribution of anticancer drugs within the entire tumor volume to deliver lethal concentrations to resistant cancer cells and tumor-initiating cancer stem cells. However, penetration of small molecular weight chemotherapeutic agents and drug-loaded polymeric and lipid particles into the hypoxic and necrotic regions of solid tumors remains a significant challenge. This article reports the results of pulsed ultrasound enhanced penetration of nano-sized fluorescent particles into MCF-7 breast cancer spheroids (300-350 μm diameter) as a function of particle size and charge. With pulsed ultrasound application in the presence of microbubbles, small (20 nm) particles achieve 6-20 folds higher penetration and concentration in the spheroid's core compared to those not exposed to ultrasound. Increase in particle size to 40 nm and 100 nm results in their effective penetration into the spheroid's core to 9 and 3 folds, respectively. In addition, anionic carboxylate particles achieved higher penetration (2.3, 3.7, and 4.7 folds) into the core (0.25r) of MCF-7 breast cancer spheroids compared to neutral (2.2, 1.9, and 2.4 folds) and cationic particles (1.5, 1.4 and 1.9 folds) upon US exposure for 30, 60, and 90 seconds under the same experimental conditions. These results demonstrate the feasibility of utilizing pulsed ultrasound to increase the penetration of nano-sized particles into MCF-7 spheroids mimicking tumor tissue. The effects of particle properties on the penetration enhancement were also illustrated.
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