Treatment of bladder cancer by geoinspired synthetic chrysotile nanocarrier-delivered circPRMT5 siRNA

Biomaterials Research - Tập 26 - Trang 1-20 - 2022
Chunping Yu1,2,3, Yi Zhang4, Ning Wang2,3, Wensu Wei2,3, Ke Cao5, Qun Zhang6, Peiying Ma4, Dan Xie3, Pei Wu7, Biao Liu1, Jiahao Liu1, Wei Xiang1, Xing Hu1, Xuewen Liu5, Jianfei Xie8, Jin Tang1, Zhi Long1, Long Wang1, Hongliang Zeng9, Jianye Liu1
1Department of Urology, The Third Xiangya Hospital of Central South University, Changsha, China
2Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China
3State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
4School of Minerals Processing and Bioengineering, Central South University, Changsha, China
5Department of Onology, The Third Xiangya Hospital of Central South University, Changsha, China
6Department of Radiotherapy, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
7Department of Operation Center, The Second Xiangya Hospital of Central South University, Changsha, China
8Department of Nursing, The Third Xiangya Hospital of Central South University, Changsha, China
9Research Institute of Chinese Medicine, Hunan academy of Chinese Medicine, Changsha, China

Tóm tắt

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. 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. 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. The results highlight the potential therapeutic utility of SCNTs/si-circPRMT5 to deliver si-circPRMT5 to treat bladder cancer.

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Biomaterials Research

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