Targeting of liposomes via PSGL1 for enhanced tumor accumulation.
Targeting of liposomes via PSGL1 for enhanced tumor accumulation.
复制标题
通过 PSGL1 靶向脂质体以增强肿瘤积累。
DOI：
10.1007/s11095-012-0875-5
复制
发表时间：
2013-02
影响因子：
3.7
通讯作者：
Coussios, Constantin C.
中科院分区：
文献类型：
--
作者：
Carlisle, Robert;Seymour, Leonard W.;Coussios, Constantin C.
利用P-选择素糖蛋白配体1（PSGL 1）介导的与肿瘤相关内皮细胞上上调的选择素分子的结合，改善脂质体向肿瘤的递送。PSGL 1的取向和脂质体的表面上，以实现最佳的选择素结合使用一种新的链霉亲和素-蛋白G接头分子。PSGL 1脂质体与E-selectin的负载允许它们与e-选择素和活化的HUVEC的结合在体外定量，并且使用鼠模型在体内测试它们的稳定性、药代动力学和肿瘤累积。PSGL 1脂质体显示出比用不含选择素结合结构域的配体修饰的相同配制的对照脂质体高5倍（p < 0.05）的选择素结合。当添加到HUVEC中时，PSGL 1脂质体显示出比对照脂质体大>7倍（p < 0.001）的附着。在体内研究中，PSGL 1脂质体显示出与对照脂质体相似的稳定性和循环，但证明了递送至肿瘤的水平提高>3倍（p < 0.05）。本文所述的技术和策略可能有助于临床改善脂质体药物递送剂的选择性和有效性。本文的在线版本（doi：10.1007/s11095-012-0875-5）包含补充材料，可供授权用户使用。
To improve the delivery of liposomes to tumors using P-selectin glycoprotein ligand 1 (PSGL1) mediated binding to selectin molecules, which are upregulated on tumorassociated endothelium. PSGL1 was orientated and presented on the surface of liposomes to achieve optimal selectin binding using a novel streptavidin-protein G linker molecule. Loading of PSGL1 liposomes with luciferin allowed their binding to e-selectin and activated HUVEC to be quantified in vitro and their stability, pharmacokinetics and tumor accumulation to be tested in vivo using murine models. PSGL1 liposomes showed 5-fold (p < 0.05) greater selectin binding than identically formulated control liposomes modified with ligand that did not contain the selectin binding domain. When added to HUVEC, PSGL1 liposomes showed >7-fold (p < 0.001) greater attachment than control liposomes. In in vivo studies PSGL1 liposomes showed similar stability and circulation to control liposomes but demonstrated a >3-fold enhancement in the level of delivery to tumors (p < 0.05). The technologies and strategies described here may contribute to clinical improvements in the selectivity and efficacy of liposomal drug delivery agents. The online version of this article (doi:10.1007/s11095-012-0875-5) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
5.4
作者：
Korokhov, N;Mikheeva, G;Krasnykh, V
通讯作者：
Krasnykh, V
影响因子：
5.1
作者：
Lievens, J;Snoeys, J;De Geest, B
通讯作者：
De Geest, B
影响因子：
2.3
作者：
Mayer, B;Spatz, H;Schildberg, FW
通讯作者：
Schildberg, FW
影响因子：
10.8
作者：
Deckers, Roel;Moonen, Chrit T. W.
通讯作者：
Moonen, Chrit T. W.
影响因子：
3.5
作者：
Brujan, EA;Ikeda, T;Matsumoto, Y
通讯作者：
Matsumoto, Y