Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan Province 450046, PR China; School of Pharmaceutical Sciences, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou, Henan Province 450001, PR China.
Center for Quantitative Biology, Peking University, Beijing 100871, PR China.
Int J Pharm. 2023 Jul 25;642:123044. doi: 10.1016/j.ijpharm.2023.123044. Epub 2023 May 12.
Dysregulation of microRNAs (miRNAs) expression is closely related to cancers and managing miRNA expression holds great promise for cancer therapy. However, their wide clinical application has been hampered by their poor stability, short half-life and non-specific biodistribution in vivo. Herein, a novel biomimetic platform designated as RHAuNCs-miRNA for improved miRNA delivery was prepared through wrapping miRNA-loaded functionalized Au nanocages (AuNCs) with red blood cell (RBC) membrane. RHAuNCs-miRNA not only successfully loaded miRNAs but also effectively protected them from enzymatic degradation. With good stability, RHAuNCs-miRNA had the characteristics of photothermal conversion and sustained release. Cellular uptake of RHAuNCs-miRNA by SMMC-7721 cells was in a time-dependent manner via clathrin- and caveolin-mediated endocytosis. The uptake of RHAuNCs-miRNAs was affected by cell types and improved by mild near infrared (NIR) laser irradiation. More importantly, RHAuNCs-miRNA exhibited a prolonged circulation time without the occurrence of accelerated blood clearance (ABC) in vivo, resulting in efficient delivery to tumor tissues. This study may demonstrate the great potential of RHAuNCs-miRNA for improved miRNAs delivery.
miRNAs 表达失调与癌症密切相关，而调控 miRNA 表达为癌症治疗带来了很大的希望。然而，由于其在体内的稳定性差、半衰期短和非特异性生物分布，其广泛的临床应用受到了阻碍。在此，通过用红细胞（RBC）膜包裹负载 miRNA 的功能化金纳米笼（AuNCs），制备了一种新型仿生平台 RHAuNCs-miRNA 以改善 miRNA 的递呈。RHAuNCs-miRNA 不仅成功负载了 miRNA，而且还能有效地保护其免受酶的降解。具有良好的稳定性，RHAuNCs-miRNA 具有光热转换和持续释放的特性。SMMC-7721 细胞通过网格蛋白和小窝蛋白介导的内吞作用，以时间依赖性方式摄取 RHAuNCs-miRNA。RHAuNCs-miRNAs 的摄取受细胞类型的影响，并通过温和的近红外（NIR）激光照射得到改善。更重要的是，RHAuNCs-miRNA 在体内没有发生加速血液清除（ABC），从而延长了循环时间，有效地将 miRNA 递送到肿瘤组织。本研究可能表明 RHAuNCs-miRNA 在改善 miRNA 递呈方面具有巨大的潜力。
