Fe-doped chrysotile nanotubes containing siRNAs to silence SPAG5 to treat bladder cancer.
Fe-doped chrysotile nanotubes containing siRNAs to silence SPAG5 to treat bladder cancer.
复制标题
含有 siRNA 的铁掺杂温石棉纳米管可沉默 SPAG5 以治疗膀胱癌
DOI：
10.1186/s12951-021-00935-z
复制
发表时间：
2021-06-23
影响因子：
10.2
通讯作者：
Cao K
中科院分区：
文献类型：
--
作者：
Liu J;Zhang Y;Zeng H;Wang L;Zhang Q;Wu P;Liu X;Xie H;Xiang W;Liu B;Liu J;Liu X;Xie J;Tang J;Long Z;He L;Xiao M;Xiang L;Cao K
背景
对于某些人类癌症，精子相关抗原5（SPAG 5）对其发展和进展发挥重要作用。然而，针对SPAG 5的RNA干扰（RNAi）是否具有抗肿瘤作用尚未在临床上确定。
结果
结果表明，Fe掺杂的纤蛇纹石纳米管（FeSiNTs）具有相对均匀的外径（15-25 nm）和内径（7-8 nm），长度为几百nm，可有效地递送针对SPAG 5癌基因（siSPAG 5）的siRNA。这些纳米材料被设计用于延长siSPAG 5在血液中的半衰期，增加肿瘤细胞特异性摄取，并最大限度地提高SPAG 5沉默的效率。在体外，携带siSPAG 5的FeSiNT抑制膀胱癌细胞的生长、迁移和侵袭。在体内，FeSiNTs在三种膀胱肿瘤模型（尾静脉注射肺转移模型、原位膀胱癌模型和皮下模型）中抑制生长和转移，没有明显的毒性。从机制上讲，我们表明FeSiNTs/siSPAG 5抑制PI 3 K/AKT/mTOR信号传导，从而抑制肿瘤细胞的生长和进展。
结论
结果强调了FeSiNT/siSPAG 5没有引起先天免疫应答的激活，也没有引起任何全身毒性，表明FeSiNT/siSPAG 5递送siSPAG 5以治疗膀胱癌的可能的治疗效用。
图形摘要
Background
For certain human cancers, sperm associated antigen 5 (SPAG5) exerts important functions for their development and progression. However, whether RNA interference (RNAi) targeting SPAG5 has antitumor effects has not been determined clinically.
Results
The results indicated that Fe-doped chrysotile nanotubes (FeSiNTs) with a relatively uniform outer diameter (15–25 nm) and inner diameter (7–8 nm), and a length of several hundred nanometers, which delivered an siRNA against the SPAG5 oncogene (siSPAG5) efficiently. The nanomaterials were designed to prolong the half-life of siSPAG5 in blood, increase tumor cell-specific uptake, and maximize the efficiency of SPAG5 silencing. In vitro, FeSiNTs carrying siSPAG5 inhibited the growth, migration, and invasion of bladder cancer cells. In vivo, the FeSiNTs inhibited growth and metastasis in three models of bladder tumors (a tail vein injection lung metastatic model, an in-situ bladder cancer model, and a subcutaneous model) with no obvious toxicities. Mechanistically, we showed that FeSiNTs/siSPAG5 repressed PI3K/AKT/mTOR signaling, which suppressed the growth and progression of tumor cells.
Conclusions
The results highlight that FeSiNTs/siSPAG5 caused no activation of the innate immune response nor any systemic toxicity, indicating the possible therapeutic utility of FeSiNTs/siSPAG5 to deliver siSPAG5 to treat bladder cancer.
Graphic abstract
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影响因子：
46.9
作者：
Judge, AD;Sood, V;MacLachlan, I
通讯作者：
MacLachlan, I
DOI：
10.1111/j.1525-1438.2006.00384.x
发表时间：
2006-03-01
影响因子：
4.8
作者：
Niu, XY;Peng, ZL;Wang, P
通讯作者：
Wang, P
影响因子：
9.7
作者：
Cho, Hee Jun;Kim, Jin Koo;Choe, Yong-Kyung
通讯作者：
Choe, Yong-Kyung
影响因子：
29.4
作者：
Dawson, Jonathan I.;Oreffo, Richard O. C.
通讯作者：
Oreffo, Richard O. C.
影响因子：
10.2
作者：
Ryu YC;Kim KA;Kim BC;Wang HD;Hwang BH
通讯作者：
Hwang BH