Progress in cancer drug delivery based on AS1411 oriented nanomaterials

Abstract

Targeted cancer therapy has become one of the most important medical methods because of the spreading and metastatic nature of cancer. Based on the introduction of AS1411 and its four-chain structure, this paper reviews the research progress in cancer detection and drug delivery systems by modifying AS1411 aptamers based on graphene, mesoporous silica, silver and gold. The application of AS1411 in cancer treatment and drug delivery and the use of AS1411 as a targeting agent for the detection of cancer markers such as nucleoli were summarized from three aspects of active targeting, passive targeting and targeted nucleic acid apharmers. Although AS1411 has been withdrawn from clinical trials, the research surrounding its structural optimization is still very popular. Further progress has been made in the modification of nanoparticles loaded with TCM extracts by AS1411. Graphical Abstract

Aptamer-programmable adeno-associated viral vectors as a novel platform for cell-specific gene transfer

“…We used three different cancer cell lines, MCF-7, A549, and HeLa, which have been extensively employed for AS1411 aptamer characterization. 19 Notably, the luciferase activity from the AS1411-DJR/A-N589 was massively reduced at the dose of 10 μM antidote in all three cell lines, whereas the unconjugated Nε-DJR/A-N589 did not show any inhibition ( Figures 5 E–5G). In addition, we saw that as little as 1 μM antidote could partially inhibit the AS1411-DJR/A-N589 transduction in MCF-7 and even more clearly in HeLa cells ( Figure 5 G).…”

“… 34 As proof of concept, we decided to evaluate one of the most characterized DNA aptamers utilized in cancer research, AS1411. 19 To conjugate the AS14411 aptamer to the Nε-AAV, we needed to first make a conjugable DBCO-AS1411 molecule. To this end, we combined a DBCO-PEG-NHS with an amine (NH 2 ) modified AS1411 aptamer to create DBCO-PEG-AS1411 ( Figure 5 A).…”

“… 17 The high versatility of aptamers and their remarkable affinity for specific ligands allowed for rapid development and use in clinical trials. 18 In particular, the AS1411 DNA aptamer has been extensively characterized in the cancer research field, 19 , 20 and a phase I/II clinical trial was also completed to assess its safety and efficacy in patients. 21 Furthermore, a recently described E3 RNA aptamer has also been characterized to specifically target and internalize into multiple cancer cells.…”

Aptamers used for molecular imaging and theranostics - recent developments

“…A phase II study in patients with advanced renal cell carcinoma (RCC) that had not responded to tyrosine kinase inhibitor therapy, however, showed no significant anticancer effects 150 . Despite this, AS1411 is now one of the most often used aptamers for imaging and targeted drug delivery, with less focus on the innate antiproliferative effect 151 . Other therapeutic aptamers in the clinical pipeline include aptamers for macular degeneration, diabetes, inflammation, coagulation disorders, inflammation and oncology 152 .…”

An assembly-inducing PDC enabling the efficient nuclear delivery of nucleic acid for cancer stem-like cell suppression

“…[8][9][10] Although AS1411 is widely attached to nanoparticles as a cancer-targeting ligand by interacting with nucleolin on the cancer cell membrane, AS1411 kills cancer cells through cellular mechanisms. [11][12][13] Thus, there is an urgent need for the development of delivery systems that can effectively transport AS1411 into the cell nucleus.…”