Moffatt Stanley, Cristiano Richard J
Laboratory of Experimental Therapeutics, Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, 77030, USA.
Int J Pharm. 2006 Jul 6;317(1):10-3. doi: 10.1016/j.ijpharm.2006.04.011. Epub 2006 May 19.
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-betagal 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-betagal 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 48 h. 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.
J591单克隆抗体（mAb）对前列腺癌细胞（PCA）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（聚乙二醇化J591）与水杨基异羟肟酸（SHA）衍生的聚乙烯亚胺（PEI）/DNA-β-半乳糖苷酶载体偶联，以研究通过包封靶向PCA细胞中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-β-半乳糖苷酶多聚体。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，以普朗尼克F68三嵌段共聚物作为对照，在0.25%（w/v）的最佳浓度下基因转染水平提高了8-10倍。转染效率的提高归因于在PLGA-PEG-PLGA三嵌段共聚物存在下放射性标记质粒的内化和摄取增加。含有SHA-PEI复合pDNA的微粒中质粒DNA（pDNA）的释放最初几乎没有突释，随后在48小时内释放5%。此后释放加速，28天后约60%被释放。去卷积共聚焦显微镜显示多聚体/微粒制剂定位于细胞核，这与没有PLGA-PEG-PLGA的多聚体相反，表明可以利用最佳浓度的PLGA-PEG-PLGA三嵌段共聚物来增强J591介导的PCA细胞靶向的内吞过程。
