Self-assembled fluorescent hybrid nanoparticles-mediated collaborative lncRNA CCAT1 silencing and curcumin delivery for synchronous colorectal cancer theranostics

Journal of Nanobiotechnology

Xinyue Cui¹  Xiongwei Deng¹  Jianqing Lu¹  Xuan Wang²  Zian Pan²  Yan Wu²  Fan Jia²  Yunhao Li³ 

[1] CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, 100190, Beijing, China;CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, 100190, Beijing, China;University of Chinese Academy of Sciences, 100049, Beijing, People’s Republic of China;Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, 100730, Beijing, People’s Republic of China;

关键词: LncRNA CCAT1;    Curcumin;    Combinational therapy;    Co-delivery;    RNAi;    Theranostic nanoparticles;   

DOI  :  10.1186/s12951-021-00981-7

来源: Springer

【 摘 要 】

BackgroundCancer synergistic therapy strategy in combination with therapeutic gene and small molecule drug offers the possibility to amplify anticancer efficiency. Colon cancer-associated transcript-1 (CCAT1) is a well identified oncogenic long noncoding RNA (lncRNA) exerting tumorigenic effects in a variety of cancers including colorectal cancer (CRC).ResultsIn the present work, curcumin (Cur) and small interfering RNA targeting lncRNA CCAT1(siCCAT1) were co-incorporated into polymeric hybrid nanoparticles (CSNP), which was constructed by self-assembling method with two amphiphilic copolymers, polyethyleneimine-poly (d, l-lactide) (PEI-PDLLA) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol) (DSPE-mPEG). Owing to the multicolor fluorescence characteristics of PEI-PDLLA, the constructed CSNP could be served as a theranostic nanomedicine for synchronous therapy and imaging both in vitro and in vivo. Resultantly, proliferation and migration of HT-29 cells were efficiently inhibited, and the highest apoptosis ratio was induced by CSNP with coordination patterns. Effective knockdown of lncRNA CCAT1 and concurrent regulation of relevant downstream genes could be observed. Furthermore, CSNP triggered conspicuous anti-tumor efficacy in the HT-29 subcutaneous xenografts model with good biosafety and biocompatibility during the treatment.ConclusionOn the whole, our studies demonstrated that the collaborative lncRNA CCAT1 silencing and Cur delivery based on CSNP might emerge as a preferable and promising strategy for synergetic anti-CRC therapy.Graphic abstract

【 授权许可】

CC BY