Characterization of aptamer-mediated gene delivery system for liver cancer therapy

Abstract

Liver cancer is a fatal disease with limited therapy options. The recombinant adenovirus expressing tumor-suppressor gene of PTEN (Ad5-PTEN) showed effective antitumor activity against liver cancer. However, its disadvantages produced great limitation on its application, especially its nonspecific and toxicity to normal cells and tissues. The epithelial cell adhesion molecule (EpCAM) is over-expressed in some liver cancer cells and an RNA aptamer EpDT3 could specially target to EpCAM-positive cells. Based on this founding, we aimed to design a kind of gene delivery system of EpDT3-mediated Ad5-PTEN (EpDT3-PEG-Ad5-PTEN, EPAP) in which polyethylene glycol was used to be a linker to conjugate EpDT3 with Ad5-PTEN. This strategy may overcome the disadvantages of naked Ad5-PTEN and enhance the antitumor effect on liver cancer. The SDS-PAGE electrophoresis, TBE-PAGE electrophoresis and fluorescence detection were conducted to confirm the successful preparation of EPAP. Compared with the naked Ad5-PTEN, EPAP showed significant anti-proliferative and anti-migratory activities against HepG2 cells. EPAP also showed selective and precise target ability to EpCAM-positive HepG2 cells in vivo. Therefore, EPAP may be further explored as a novel effective anticancer drug for malignant liver cancer.

Targeting Liver Cancer Stem Cells Using Engineered Biological Nanoparticles for the Treatment of Hepatocellular Cancer

“…The approaches taken could be extended to other cell surface markers by developing specific apt and used in combination with EpCAM to improve targeting to cancer cells. Likewise, other types of EpCAM‐targeting apt nanoparticles could be developed for gene targeting or drug delivery into cancer cells …”

Selection and preliminary application of a single stranded DNA aptamer targeting colorectal cancer serum

“…In this study, we used traditional real-time quantitative PCR which accounted for that our screening work don't need high instrument requirements, and it is more helpful for later application comparing to the digital PCR which is difficult to purchase such sophisticated equipment in most laboratories used by Soh's group. 13,39 Moreover, compared to ow cytometry and elisa for screening, [40][41][42] we use PCR more efficiently and conveniently. For the selection of nucleic acid aptamers targeting to the serum from lung cancer patients reported previously by our laboratory, our strategy for selection has been optimized on the basis of anterior work, and the aptamers we obtained have higher affinity under the high efficiency of keeping the number of screening rounds unchanged.…”

“…4 Nucleic acid aptamers, single stranded random oligonucleotide library articially synthesized through ligand evolution technique (SELEX) in exponential amplication, 5,6 can be used as one of the most promising tools for disease diagnosis due to their high specic affinity to targeted molecules. 7 They are also objectively measurable molecular signatures of physiological status that can be used as disease indicators or drug targets for clinical diagnosis, 8,9 imaging, 10,11 delivery 11,12 and therapy, [13][14][15] hence playing a role in precision medicine. There are already many successful studies about aptamer-mediated gene therapy on breast cancer, glioma, prostate cancer, Burkitt lymphoma, etc.…”

The use of adenoviral vectors in gene therapy and vaccine approaches

“…Another approach used for targeting tumor cells was the use of cytokine-induced killer (CIK) cells as vehicles for adenoviral delivery. CIK cells carrying adenovirus expressing anti- RAS antibody guaranteed tumor specificity in glioma, lung, and colon cancer ( Liu et al, 2018 ; Lin et al, 2019 ; Qian et al, 2021 ). Although, in a liver cancer model, CIK cells delivery did not demonstrate tumor specificity and adenoviruses were detected in different organs, even though antitumor activity was achieved ( Dai et al, 2021 ).…”

“…Ad-PTEN enhanced the doxorubicin efficacy in bladder and prostate cancer (Tanaka and Grossman, 2003;Tanaka et al, 2005) and sensitized tumor cells to cisplatin (Li D et al, 2013;Wu et al, 2015), docetaxel (Liu Z et al, 2012), to a PI3K inhibitor (Ren et al, 2012), radiotherapy (Pappas et al, 2007;Rosser et al, 2004), to TIMP-2 (Lu et al, 2004) and caffeine (Saito et al, 2003). To provide specificity to tumor cells, PTEN has been conjugated to the epithelial cell adhesion molecule (EpCAM), which resulted in better antitumor effects in liver cancer in vivo and in vitro (Liu Z et al, 2018). Oncolytic adenoviruses expressing PTEN under control of a specific promoter to prostate cancer have conferred almost complete tumor regression and high specificity in prostate cancer in vitro and in a murine model (Ding et al, 2012).…”