近日，北京大学研究者设计了一种新型的脂质体材料，这种新型的材料在药物运输过程中，可增强前列腺癌症对于siRNA吸收，为癌症的靶向治疗提供了新的策略，这一新的研究成果发表在了最近的《Biomaterials》杂志上。

在我国，前列腺癌发病率逐年上升，早期局限性前列腺癌一般采用手术或局部放疗，晚期前列腺癌首选内分泌治疗，但相当一部分患者在内分泌治疗18到24个月后从对激素依赖逐渐变为对激素不敏感，成为激素抵抗型前列腺癌（HRPC），医生在线答疑，因此药物运输的效果成为靶向治疗的重要因素之一。
 
在前列腺癌激素抵抗期间，前列腺特异性抗原（PSA）和前列腺特异性膜抗原（PSMA）保持很高的表达活性。这两种蛋白不仅仅作为前列腺癌的特异性标志物， 同时激活功能性分子的传递。北京大学研究者开发了一种双重修饰标记的脂质体材料，结合到PSA和PSMA介导siRNA在细胞和体内的跨膜运输。研究结果显示这种双重的修饰方式，在增加PC细胞对siRNA的吸收和识别起到非常重要的作用，减少了其它细胞和组织对siRNA的非特异性吸收。通过锐博生物提供的特异性siRNA(RiboBio.CO.,LTD,Guangzhou,China)对细胞凋亡相关基因PLK-1的干扰实验，证实使用这种新型脂质材料包裹的siRNA，显著提升细胞对siRNA的吸收，对PLK-1基因的干扰明显增强，从而增强了siRNA 促使PC肿瘤细胞的凋亡。这一新型的脂质体材料修饰方法为前列腺癌靶向治疗提供了一个新的有效策略。

锐博生物提供覆盖人全基因组所有基因的常规siRNA，同时设计合成高特异性的任何物种siRNA，更多信息，医生在线答疑，欢迎访问或来电4006860075咨询！

锐博生物推荐原文检索：

PSA-responsive and PSMA-mediated multifunctional liposomes for targeted therapy of prostate cancer

Bai Xiang, Da-Wen Dong, et.al. Biomaterials 2013 Jun 15. PMID:23777916

Abstract；In the hormone-refractory stage of prostate cancer (PC), the expression of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) often remains highly active. Accumulating studies have demonstrated that these two proteins are attractive targets for specific delivery of functional molecules to advanced PC, not merely as potential sensitive markers for PC detection. In this study, we constructed a dual-modified liposome that incorporated PSA-responsive and PSMA-mediated liposomes and potentially offers double selectivity for PC. The folate moiety binds quickly to PSMA-positive tumors, and the PSA-responsive moiety is cleaved by PSA that was enriched in tumor tissues. The activated liposomes (folate and cell-penetrating peptides dual-modifications) are subsequently taken up by the tumor cells via polyarginine's penetrating effects and receptor-mediated endocytosis. To corroborate these assumptions, a series of experiments were conducted, including PSA-responsive peptide hydrolysis kinetics, cellular uptake, internalization mechanism and escape from endosomes in PC-3 and/or 22Rv1 cells, biodistribution and antitumor activity of siRNA-loaded liposomes after systemic administration, gene silencing and cell apoptosis in vitro and in vivo. The results reveal that multivalent interactions play a key role in enhancing PC cell recognition and uptake while reducing nonspecific uptake. The dual-modified liposomes carrying small interfering RNA (siRNA) have significant advantages over the control liposomes, including single-modified (folate, CPP, PSA-responsive only) and non-modified liposomes. The dual-modified liposomes elevated cellular uptake, downregulated expression of polo-like kinase 1 (PLK-1) and augmented cell apoptosis in prostate tumor cells. The entry of the dual-modified liposomes into 22Rv1 cells occurred via multiple endocytic pathways, including clathrin-mediated endocytosis and macropinocytosis, followed by an effective endosomal escape of the entrapped siRNA into the cytoplasm. In vivo studies conducted on a 22Rv1 xenograft murine model demonstrated that the dual-modified liposomes demonstrated the maximized accumulation, retention and knockdown of PLK-1 in tumor cells, as well as the strongest inhibition of tumor growth and induction of tumor cell apoptosis. In terms of targeting capacity and therapeutic potency, the combination of a PSA-responsive and PSMA-mediated liposome presents a promising platform for therapy and diagnosis of PSMA/PSA-positive PC.