Dually regulating the proliferation and the immune microenvironment of melanoma via nanoparticle-delivered siRNA targeting onco-immunologic CD155
Dually regulating the proliferation and the immune microenvironment of melanoma via nanoparticle-delivered siRNA targeting onco-immunologic CD155
复制标题
通过纳米颗粒递送的 siRNA 靶向肿瘤免疫 CD155 双重调节黑色素瘤的增殖和免疫微环境
DOI：
10.1039/d0bm01420f
复制
发表时间：
2020
影响因子：
6.6
通讯作者：
Jun Wang
中科院分区：
文献类型：
--
作者：
Yan Wang;Ying-Li Luo;Yi-Fang Chen;Zi-Dong Lu;Yue Wang;Anna Czarna;Song Shen;Cong-Fei Xu;Jun Wang
研究表明，同时调控肿瘤细胞增殖和抑制肿瘤免疫微环境（TIME）可以达到更好的治疗效果。然而，肿瘤细胞增殖的靶点和肿瘤的时间不同，这极大地限制了肿瘤治疗的发展。最近的一项研究发现，CD 155是黑色素瘤细胞和黑色素瘤浸润巨噬细胞中高度表达的脊髓灰质炎病毒受体，它既是癌基因又是免疫检查点。因此，推测靶向CD 155可以带来双重治疗效果。在此，我们提出了沉默黑色素瘤细胞和黑色素瘤浸润性巨噬细胞的CD 155的纳米颗粒递送的小干扰RNA（siRNA）靶向CD 155（siCD 155）。我们将siCD 155封装到阳离子脂质辅助纳米颗粒（CLANsiCD 155）中，并证明静脉注射CLANsiCD 155可以有效地将siCD 155递送到黑色素瘤细胞和黑色素瘤浸润巨噬细胞中。CD 155在黑色素瘤细胞中的下调直接抑制其增殖，同时，CD 155在黑色素瘤浸润的巨噬细胞中的下调增加NK细胞和T细胞的活化。由于这种双重作用，CLANsiCD 155显著抑制B16-F10黑色素瘤的生长。我们的研究表明，纳米颗粒递送siCD 155可能是一种简单但有效的抑制肿瘤增殖和重新编程TIME的策略。
Studies have shown that the simultaneous regulation of tumor cell proliferation and the suppressive tumor immune microenvironment (TIME) could achieve better therapeutic effects. However, the targets of the proliferation and the TIME are different, which greatly limits the development of cancer therapy. A recent study found CD155, a highly expressed poliovirus receptor in melanoma cells and melanoma-infiltrating macrophages, functions as both an oncogene and immune checkpoint. Thus, it is supposed that targeting CD155 could bring dual therapeutic effects. Herein, we propose silencing the CD155 of melanoma cells and melanoma-infiltrating macrophages by a nanoparticle-delivered small interference RNA (siRNA) targeting CD155 (siCD155). We encapsulated siCD155 into cationic lipid-assisted nanoparticles (CLANsiCD155) and demonstrated that the intravenous injection of CLANsiCD155 could efficiently deliver siCD155 into melanoma cells and melanoma-infiltrating macrophages. The downregulation of CD155 in melanoma cells directly inhibited their proliferation, and meanwhile, the downregulation of CD155 in melanoma-infiltrating macrophages increased the activation of NK cells and T cells. Owing to this dual effect, CLANsiCD155 significantly inhibited the growth of B16-F10 melanoma. Our study suggests that nanoparticle-delivered siCD155 may be a simple but effective strategy for inhibiting tumor proliferation and reprogramming TIME.