PEGylated J591 mAb loaded in PLGA-PEG-PLGA tri-block copolymer for targeted delivery: in vitro evaluation in human prostate cancer cells.
PEGylated J591 mAb loaded in PLGA-PEG-PLGA tri-block copolymer for targeted delivery: in vitro evaluation in human prostate cancer cells.
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DOI：
10.1016/j.ijpharm.2006.04.011
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发表时间：
2006-07
影响因子：
5.8
通讯作者：
S. Moffatt;R. Cristiano
中科院分区：
文献类型：
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作者：
S. Moffatt;R. Cristiano
J591单克隆抗体（mAb）对前列腺癌（PCA）细胞上的前列腺特异性膜抗原（PSMA）具有高亲和力。我们将聚乙二醇-J591（PEG化J591）偶联到水杨基异羟肟酸（SHA）衍生的聚乙烯亚胺（PEI）/DNA-βgal载体上，以研究通过封装靶向PCA细胞中的PSMA的特异性和效率。通过苯基（二）硼酸（PDBA）与SHA分子之间的高亲和力相互作用促进偶联，产生J591/PEG/PEI/DNA-βgal复合物。在用聚（d，l-乳酸-共-乙醇酸）-b-聚乙二醇-b-聚（d，l-乳酸-共-乙醇酸）（PLGA-PEG-PLGA）三嵌段共聚物包封后，使用Pluronic F68三嵌段共聚物作为对照，在0.25%（w/v）的最佳浓度下获得8-10倍的基因转染水平增加。增强的转染效率归因于在PLGA-PEG-PLGA三嵌段共聚物存在下放射性标记的质粒的内化和摄取增加。质粒DNA（pDNA）从含有SHA-PEI复合的pDNA的微粒中的释放显示出很少的初始突释，随后在48小时内释放5%。此后释放加速，28天后释放约60%。去卷积共聚焦显微镜显示，与没有PLGA-PEG-PLGA的聚合复合物相反，聚合复合物/微粒制剂定位于细胞核中，表明PLGA-PEG-PLGA三嵌段共聚物的最佳浓度可用于增强J591介导的PCA细胞靶向的内吞过程。
J591 monoclonal antibody (mAb) has high affinity for prostate specific membrane antigen (PSMA) on prostate cancer (PCA) cells. We coupled polyethylene glycol-J591 (PEGylated J591) to a salicyl hydroxamic acid (SHA)–derivatized polyethylenimine (PEI)/DNA-βgal vector to investigate the specificity and efficiency of targeting PSMA in PCA cells through encapsulation. Coupling was facilitated via the high affinity interaction between phenyl(di)boronic acid (PDBA) and SHA molecules yielding J591/PEG/PEI/DNA-βgal polyplex. After encapsulation with poly(d,l-lactic-co-glycolic acid)-b-polyethylene glycol-b-poly(d,l-lactic-co-glycolic acid) (PLGA-PEG-PLGA) tri-block copolymer, 8–10-fold increment of gene transfection levels were attained at the optimum concentration of 0.25% (w/v) using Pluronic F68 tri-block copolymer as a control. The enhanced transfection efficiency was attributed to increased internalization and uptake of the radiolabeled plasmid in the presence of PLGA-PEG-PLGA tri-block copolymer. The release of plasmid DNA (pDNA) from microparticles containing SHA–PEI-complexed pDNA showed little initial burst release followed by a 5% release over 48h. The release accelerated thereafter and approximately 60% was released after 28 days. Deconvolution confocal microscopy showed polyplex/microparticle formulation localized in the cell nucleus as opposed to the polyplex without PLGA-PEG-PLGA indicating that an optimal concentration of PLGA-PEG-PLGA tri-block copolymer can be utilized to enhance endocytic process of J591-mediated targeting of PCA cells.