Engineering lipid vesicles of enhanced intratumoral transport capaabilities:: Correlating liposome characteristics with penetration into human prostate tumor spheroids
Engineering lipid vesicles of enhanced intratumoral transport capaabilities:: Correlating liposome characteristics with penetration into human prostate tumor spheroids
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DOI：
10.1081/lpr-200064953
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发表时间：
2005-01-01
影响因子：
4.4
通讯作者：
Sgouros, G
中科院分区：
文献类型：
--
作者：
Kostarelos, K;Emfietzoglou, D;Sgouros, G
脂质体已被广泛应用于递送系统，特别是与癌症治疗的发展有关。许多基于脂质体的药物目前正在临床或临床试验中用于治疗多种肿瘤类型；然而，关于脂质体与实体性或转移性肿瘤结节相互作用的系统研究很少。本研究描述了脂质体与无血管人前列腺（LNCaP-LN3）肿瘤球体的体外相互作用。通过共聚焦激光扫描显微镜研究了不同物理化学特性的荧光标记脂质体递送系统穿透多细胞肿瘤球体的能力。研究了脂质体的各种特性和实验参数，包括脂质双层组成、脂质体与球体相互作用的持续时间、平均脂质体大小、脂质体的空间稳定性。阳离子脂质体与球体之间的静电结合效率很高；然而，它阻碍了肿瘤球体更深层的囊泡的渗透，表面中性的小单层脂质体的结合效率不高，但在靠近肿瘤核心的地方表现出增强的渗透运输能力。聚合物包被的（空间稳定的）脂质体几乎没有表现出与球体的相互作用，这表明它们在无血管组织中的有限扩散可能是它们对抗微转移的限制步骤。多细胞肿瘤球体被用作实体瘤间质模型，这些实体瘤间质与能够从微血管外渗的传递系统有关，或者作为血管前化微转移的模型。该研究表明，脂质体和其他药物递送系统与多细胞肿瘤球体之间的相互作用可以为优化实体或微转移性肿瘤递送和靶向策略提供至关重要的信息。
Liposomes have been widely used delivery systems, particularly relevant to the development of cancer therapeutics. Numerous liposome-based drugs are in the clinic or in clinical trials today against multiple tumor types; however, systematic studies of liposome interactions with solid or metastatic tumor nodules are scarce. This study is describing the in vitro interaction between liposomes and avascular human prostate (LNCaP-LN3) tumor spheroids. The ability of fluorescently labelled liposomal delivery systems of varying physicochernical characteristics to penetrate within multicellular tumor spheroids has been investigated by confocal laser scanning microscopy. A variety of liposome characteristics and experimental parameters were investigated, including lipid bilayer composition, duration of liposome-spheroid interaction, mean liposome size, steric stabilization of liposomes. Electrostatic binding between cationic liposomes and spheroids was very efficient; however, it impeded any significant penetration of the vesicles within deeper layers of the tumor spheroid Small unilamellar liposomes of neutral surface character did not bind as efficiently but exhibited enhanced penetrative transport capabilities closer to the tumor core. Polymer-coated (sterically stabilised) liposomes exhibited almost no interaction with the spheroid, indicating that their limited diffusion within avascular tissues may be a limiting step for their use against micrometastases. Multicellular tumor spheroids were used as models of solid tumor interstitium relevant to delivery systems able to extravasate from the microcapillaries or as models of prevascularized micrometastases. This study illustrates that interactions between liposomes and other drug delivery systems with multicellular tumor spheroids can offer critically important information with respect to optimizing solid or micrometastatic tumor delivery and targeting strategies.