The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Nanoscale. 2022 Oct 6;14(38):14014-14022. doi: 10.1039/d2nr02200a.
Small interfering RNA (siRNA) is ideal for gene silencing through a sequence-specific RNA interference process. The redundancy and complexity of molecular pathways in cancer create a need for multiplexed targeting that can be achieved with multiplexed siRNA delivery. Here, we delivered multiplexed siRNA with a PSMA-targeted biocompatible dextran nanocarrier to downregulate CD46 and PD-L1 in PSMA expressing prostate cancer cells. The selected gene targets, PD-L1 and CD46, play important roles in the escape of cancer cells from immune surveillance. PSMA, abundantly expressed by prostate cancer cells, allowed the prostate cancer-specific delivery of the nanocarrier. The nanocarrier was modified with acid cleavable acetal bonds for a rapid release of siRNA. Cell imaging and flow cytometry studies confirmed the PSMA-specific delivery of CD46 and PD-L1 siRNA to high PSMA expressing PC-3 PIP cells. Immunoblot, qRT-PCR and flow cytometry methods confirmed the downregulation of CD46 and PD-L1 following treatment with multiplexed siRNA.
小干扰 RNA（siRNA）通过序列特异性 RNA 干扰过程非常适合基因沉默。癌症中分子途径的冗余和复杂性需要进行多重靶向，而这可以通过多重 siRNA 递送来实现。在这里，我们使用一种靶向 PSMA 的生物相容性葡聚糖纳米载体递送电镜下观察和流式细胞术证实了，该纳米载体可特异性递送至高表达 PSMA 的 PC-3 PIP 细胞，实现 CD46 和 PD-L1 siRNA 的 PSMA 特异性递送。免疫印迹、qRT-PCR 和流式细胞术方法证实，用多重 siRNA 处理后，CD46 和 PD-L1 的表达下调。
