Abstract
The long non-coding RNA (lncRNA) MALAT1 acts as an oncogene. RNA interference (RNAi) is an effective method to control the expression of specific genes and can be used for the treatment of tumors, but an effective and safe carrier system is a significant obstacle to gene therapy. Herein, we explored the possibility of constructing an in situ bio-responsive self-assembled fluorescent gold-short hairpin RNA nanocomplex (Au–shRNA NCs) delivery system by co-incubating gold and MALAT1-shRNA for precise hepatocellular carcinoma (HCC) imaging and treatment. Due to the characteristics of the cancer microenvironment, Au–shRNA NCs self-assembled in HCC cells (HepG2) but did not occur in control cells (L02) under the same conditions. The in situ bio-responsive self-assembled Au–shRNA NCs delivery system can realize cancer cell bioimaging and promote cell uptake and endosomal escape mechanism, thereby realizing effective transfection. They effectively silenced target gene MALAT1, and with the downregulation of MALAT1, we found that several molecules involved in autophagic flux were also regulated. In vitro and tumor-bearing mouse model experiments demonstrated that the as-prepared fluorescent Au–shRNA NCs can readily realize tumor bioimaging and effectively silence the target gene MALAT1, and those autophagy-related pathway molecules were significantly downregulated, thereby exerting a tumor suppressor efficiency. This raises the possibility of realizing accurate multi-scale bio-imaging from the molecular-level with targeted gene-recognition to cancer cell imaging as well as in vivo tumor tissue imaging for the simultaneous precise cancer therapy.
Highlights
Introduction iationsLong noncoding RNAs are more than 200 nucleotides in length [1,2] and participate in numerous physiological and pathophysiological activities such as carcinogenesis and autophagy [3,4,5]
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is one of the star molecules of long non-coding RNA (lncRNA), which has been determined to participate in various processes including cell apoptosis and proliferation [11]
We analyzed the relationship between MALAT1 expression level and disease progression and prognosis in hepatocellular carcinoma (HCC) patients (Table S1)
Summary
Introduction iationsLong noncoding RNAs (lncRNAs) are more than 200 nucleotides in length [1,2] and participate in numerous physiological and pathophysiological activities such as carcinogenesis and autophagy [3,4,5]. Aberrant expression or dysfunction of lncRNAs is closely associated with various diseases [6,7,8,9]. Research findings have illustrated that lncRNAs may be involved in remodeling the tumor microenvironment and in tumor metastasis [10]. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is one of the star molecules of lncRNA, which has been determined to participate in various processes including cell apoptosis and proliferation [11]. As reported in several studies, MALAT1 serves as a potentially valuable biomarker in cancer diagnosis and prognosis [12]. It is reported that MALAT1 is a mutation factor
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