Ultrasound triggered cell death in vitro with doxorubicin loaded poly lactic-acid contrast agents.
Ultrasound triggered cell death in vitro with doxorubicin loaded poly lactic-acid contrast agents.
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DOI：
10.1016/j.ultras.2009.03.003
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发表时间：
2009-12
期刊：
影响因子：
4.2
通讯作者：
Wheatley, M. A.
中科院分区：
文献类型：
--
作者：
Eisenbrey, J. R.;Huang, P.;Hsu, J.;Wheatley, M. A.
传统的化疗通常会导致全身毒性，这也限制了需要的区域的药物水平。本文报道了两种聚乳酸（PLA）超声造影剂（UCA）的体外对比研究。两种UCA的粒径在1-2 μm之间，壳层厚度在100-200 nm之间。这些聚乳酸（PLA）UCA平台包含一个气体核心，在超声（US）场中，该气体核心可导致UCA振荡或破裂。在全身注射载药UCA并在关注区域外用US后，该平台可能会增加需要区域的药物毒性，同时通过药物的微囊化保护健康组织。在MDA-MB-231乳腺癌细胞的表面吸附和壳结合阿霉素（Dox）加载的UCA的体外毒性进行了检查，在5 MHz的超声使用脉冲重复频率为100 Hz，在不同的压力振幅。当在1.26 MPa及以上的峰值正压振幅下超声时，与游离Dox和US相比，两种平台导致等同的细胞死亡。虽然在有或没有超声作用的情况下，对于表面吸附的Dox-UCA没有观察到细胞死亡的显著变化，但是使用在壳内掺入Dox的平台的细胞死亡从16.12%增加到25.78%（p = 0.0272），接近于当在1.26MPa和更高的峰值正压振幅下超声作用时平台效力的两倍。这种机制被认为是在较高的声震压力振幅下UCA破裂的结果，导致更多的暴露药物和壳表面积以及含Dox的聚合物壳片段的细胞摄取增加。这项研究表明，壳内含有药物的聚合物UCA可用于US触发的细胞死亡。一旦在需要的区域中，US活化可用于使载体显著更有效。
Traditional chemotherapy generally results in systemic toxicity, which also limits drug levels at the area of need. Two ultrasound contrast agents (UCA), with diameters between 1-2 μm in diameter and shell thicknesses of 100-200 nm, composed of poly lactic-acid (PLA), one loaded by surface adsorption and the other loaded by drug incorporation in the shell, were compared in vitro for potential use in cancer therapy. These poly lactic-acid (PLA) UCA platforms contain a gas core that in an ultrasound (US) field can cause the UCA to oscillate or rupture. Following a systemic injection of drug loaded UCA with external application of US focused at the area of interest, this platform could potentially increase drug toxicity at the area of need, while protecting healthy tissue through microencapsulation of the drug. In vitro toxicity in MDA-MB-231 breast cancer cells of the surface-adsorbed and shell-incorporated doxorubicin (Dox) loaded UCA were examined at 5 MHz insonation using a pulse repetition frequency of 100 Hz at varying pressure amplitudes. Both platforms resulted in equivalent cell death compared to free Dox and US when insonated at peak positive pressure amplitudes of 1.26 MPa and above. While no significant changes in cell death were seen for surface adsorbed Dox-UCA with or without insonation, cell death using the platform with Dox incorporated within the shell increased from 16.12 to 25.78% (p = 0.0272), approaching double the potency of the platform when insonated at peak positive pressure amplitudes of 1.26 MPa and above. This mechanism is believed to be the result of UCA rupture at higher insonation pressure amplitudes, resulting in more exposed drug and shell surface area as well as increased cellular uptake of Dox containing polymer shell fragments. This study has shown that a polymer UCA with drug housed within the shell may be used for US triggered cell death. US activation can be used to make a carrier significantly more potent once in the area of need.
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影响因子：
10.8
作者：
Kooiman, Klazina;Bohmer, Marcel R.;van Wamel, Annemieke
通讯作者：
van Wamel, Annemieke
DOI：
10.1016/j.euje.2004.02.001
发表时间：
2004-08-01
期刊：
European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology
影响因子：
--
作者：
Dijkmans, P A;Juffermans, L J M;Kamp, O
通讯作者：
Kamp, O
影响因子：
4.2
作者：
Wheatley, Margaret A.;Forsberg, Flemming;El-Sherif, Dalia
通讯作者：
El-Sherif, Dalia
影响因子：
3.2
作者：
Narayan, P;Wheatley, MA
通讯作者：
Wheatley, MA
影响因子：
120.1
作者：
Mitragotri, S
通讯作者：
Mitragotri, S