Treatment of bladder cancer by geoinspired synthetic chrysotile nanocarrier-delivered <i>circPRMT5</i> siRNA
Chunping Yu, Yi Zhang, Ning Wang, Wensu Wei, Ke Cao, Qun Zhang, Peiying Ma, Dan Xie, Pei-Hsun Wu, Biao Liu, Jiahao Liu, Wei Xiang, Xing Hu, Xuewen Liu, Jianfei Xie, Jin Tang, Zhi Long, Long Wang, Hongliang Zeng, Jianye Liu
Abstract
BACKGROUND: Circular RNAs (circRNAs) have important functions in many fields of cancer biology. In particular, we previously reported that the oncogenic circRNA, circPRMT5, has a major role in bladder cancer progression. Therapy based on circRNAs have good prospects as anticancer strategies. While anti-circRNAs are emerging as therapeutics, the specific in vivo delivery of anti-circRNAs into cancer cells has not been reported and remains challenging. METHODS: Synthesized chrysotile nanotubes (SCNTs) with a relatively uniform length (~ 200 nm) have been designed to deliver an siRNA against the oncogenic circPRMT5 (si-circPRMT5) inhibit circPRMT5. In addition, the antitumor effects and safety evaluation of SCNTs/si-circPRMT5 was assessed with a series of in vitro and in vivo assays. RESULTS: The results showed that SCNTs/si-circPRMT5 nanomaterials prolong si-circPRMT5's half-life in circulation, enhance its specific uptake by tumor cells, and maximize the silencing efficiency of circPRMT5. In vitro, SCNTs encapsulating si-circPRMT5 could inhibit bladder cancer cell growth and progression. In vivo, SCNTs/si-circPRMT5 inhibited growth and metastasis in three bladder tumor models (a subcutaneous model, a tail vein injection lung metastatic model, and an in situ model) without obvious toxicities. Mechanistic study showed that SCNTs/si-circPRMT5 regulated the miR-30c/SNAIL1/E-cadherin axis, inhibiting bladder cancer growth and progression. CONCLUSION: The results highlight the potential therapeutic utility of SCNTs/si-circPRMT5 to deliver si-circPRMT5 to treat bladder cancer.