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- Title
Treatment of bladder cancer by geoinspired synthetic chrysotile nanocarrier-delivered circPRMT5 siRNA.
- Authors
Yu, Chunping; Zhang, Yi; Wang, Ning; Wei, Wensu; Cao, Ke; Zhang, Qun; Ma, Peiying; Xie, Dan; Wu, Pei; Liu, Biao; Liu, Jiahao; Xiang, Wei; Hu, Xing; Liu, Xuewen; Xie, Jianfei; Tang, Jin; Long, Zhi; Wang, Long; Zeng, Hongliang; Liu, Jianye
- 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.
- Publication
Biomaterials Research, 2022, Vol 26, Issue 1, p1
- ISSN
2055-7124
- Publication type
Article
- DOI
10.1186/s40824-022-00251-z