Predicting diffusive transport of cationic liposomes in 3-dimensional tumor spheroids.
Predicting diffusive transport of cationic liposomes in 3-dimensional tumor spheroids.
复制标题
预测 3 维肿瘤球体中阳离子脂质体的扩散转运。
DOI：
10.1016/j.jconrel.2014.06.050
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Au,JessieLS
中科院分区：
文献类型：
--
作者：
Wientjes,MichaelG;Yeung,BertrandZ;Lu,Ze;Wientjes,MGuillaume;Au,JessieLS
纳米技术被广泛应用于癌症研究。预测纳米颗粒在肿瘤(包括亚细胞室)中的传输和输送的模型将是有用的工具。这项研究验证了一个假设，即可以根据脂质体-细胞生物界面参数(结合、摄取、保留)和脂质体扩散系数来预测阳离子脂质体在三维(3D)系统中的扩散传输。研究了含有不同量阳离子和融合脂类(10~30 mV DOTAP或1，2-dioleoyl-sn-glycero-3-phosphoethanolamine，1~20 mV DOPE或1，2-二油酰基-3-三甲基丙烷，+0.25~+0.44 mV zeta电位)的脂质体。我们(A)在单层培养中测量了脂质体-细胞生物界面参数，(B)根据脂质体大小和球体成分计算了有效扩散系数。所得到的参数被用来模拟三维球体中脂质体的浓度-深度分布。对于DOTAP和≤含量分别为10-30%和10%的脂质体，模拟结果与实验结果基本一致，但对于掺杂量较高的脂质体，模拟结果与实验结果不一致。对于后者，对模型进行修改以考虑随时间变化的细胞外浓度降低和脂质体大小增加并没有改善预测。低掺杂和高掺杂脂质体之间的差异表明，3D系统中的掺杂特性依赖于浓度，而单层膜中没有捕获到这些特性。综上所述，我们早期和目前的研究表明，中性、阴离子和阳离子纳米颗粒(聚苯乙烯微珠和脂质体，直径20-135m m，−为49-+44m V)在3D球体中的扩散传输可以根据纳米颗粒-细胞生物界面和纳米颗粒扩散系数进行预测，但脂质体中含有10mmol%的药物除外。将该模型应用于低掺杂脂质体，表明表面电荷的变化影响了脂质体在球体内肿瘤内亚室的定位。
Nanotechnology is widely used in cancer research. Models that predict nanoparticle transport and delivery in tumors (including subcellular compartments) would be useful tools. This study tested the hypothesis that diffusive transport of cationic liposomes in 3-dimensional (3D) systems can be predicted based on liposome–cell biointerface parameters (binding, uptake, retention) and liposome diffusivity. Liposomes comprising different amounts of cationic and fusogenic lipids (10–30 mol% DOTAP or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, 1–20 mol% DOPE or 1,2-dioleoyl-3-trimethylammonium-propane, + 25 to + 44 mV zeta potential) were studied. We (a) measured liposome–cell biointerface parameters in monolayer cultures, and (b) calculated effective diffusivity based on liposome size and spheroid composition. The resulting parameters were used to simulate the liposome concentration–depth profiles in 3D spheroids. The simulated results agreed with the experimental results for liposomes comprising 10–30 mol% DOTAP and ≤ 10 mol% DOPE, but not for liposomes with higher DOPE content. For the latter, model modifications to account for time-dependent extracellular concentration decrease and liposome size increase did not improve the predictions. The difference among low- and high-DOPE liposomes suggests concentration-dependent DOPE properties in 3D systems that were not captured in monolayers. Taken together, our earlier and present studies indicate the diffusive transport of neutral, anionic and cationic nanoparticles (polystyrene beads and liposomes, 20–135 nm diameter, − 49 to + 44 mV) in 3D spheroids, with the exception of liposomes comprising > 10 mol% DOPE, can be predicted based on the nanoparticle–cell biointerface and nanoparticle diffusivity. Applying the model to low-DOPE liposomes showed that changes in surface charge affected the liposome localization in intratumoral subcompartments within spheroids.
登录
查看更多内容
[使用烟雾弹药后氯化锌烟雾中毒]。
DOI：
--
发表时间：
1984
期刊：
Ugeskrift for læger
影响因子：
--
作者：
C. Pedersen;C. P. Hansen;W. Grønfeldt
通讯作者：
W. Grønfeldt
影响因子：
120.7
作者：
Bartlett, RH;Roloff, DW;Hirschl, RB
通讯作者：
Hirschl, RB
接触氯化锌烟雾造成的伤亡
DOI：
10.1016/s0140-6736(45)91239-6
发表时间：
1945
期刊：
The Lancet
影响因子：
--
作者：
E. Evans
通讯作者：
E. Evans
影响因子：
158.5
作者：
Brower, RG;Matthay, MA;Sibbald, WJ
通讯作者：
Sibbald, WJ
影响因子：
2.7
作者：
Chian, Chih-Feng;Wu, Chin-Pyng;Perng, Wann-Cherng
通讯作者：
Perng, Wann-Cherng