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

Biomaterials Research

Jianfei Xie¹  Xuewen Liu²  Ke Cao²  Pei Wu³  Qun Zhang⁴  Wensu Wei⁵  Ning Wang⁵  Wei Xiang⁶  Biao Liu⁶  Zhi Long⁶  Jianye Liu⁶  Long Wang⁶  Xing Hu⁶  Jin Tang⁶  Jiahao Liu⁶  Chunping Yu⁷  Hongliang Zeng⁸  Peiying Ma⁹  Yi Zhang⁹  Dan Xie^1,10 

[1] Department of Nursing, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, 410013, Changsha, Hunan, China;Department of Onology, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, 410013, Changsha, Hunan, China;Department of Operation Center, The Second Xiangya Hospital of Central South University, People’s Middle Road, 410008, Changsha, Hunan, China;Department of Radiotherapy, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, 510080, Guangzhou, Guangdong, China;Department of Urology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, 510060, Guangzhou, Guangdong, China;State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, No. 651, Dongfeng Road East, 510060, Guangzhou, Guangdong, China;Department of Urology, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, 410013, Changsha, Hunan, China;Department of Urology, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, 410013, Changsha, Hunan, China;Department of Urology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, 510060, Guangzhou, Guangdong, China;State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, No. 651, Dongfeng Road East, 510060, Guangzhou, Guangdong, China;Research Institute of Chinese Medicine, Hunan Academy of Chinese Medicine, No.58, Lushan Road, 410000, Changsha, Hunan, China;School of Minerals Processing and Bioengineering, Central South University, No. 932, Lushan South, 410083, Changsha, Hunan, China;State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, No. 651, Dongfeng Road East, 510060, Guangzhou, Guangdong, China;

关键词: Synthesized chrysotile nanomaterials;    Gene therapy;    Targeted delivery;    CircPRMT5;    SiRNA;    Bladder cancer;   

DOI  :  10.1186/s40824-022-00251-z

来源: Springer

【 摘 要 】

BackgroundCircular 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.MethodsSynthesized 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.ResultsThe 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.ConclusionThe results highlight the potential therapeutic utility of SCNTs/si-circPRMT5 to deliver si-circPRMT5 to treat bladder cancer.

【 授权许可】

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