A molecular hybrid comprising AS1411 and PDGF‐BB aptamer, cholesterol, and doxorubicin for inhibiting proliferation of SW480 cells

Abstract

Cancer treatment commonly relies on chemotherapy. This treatment faces many challenges, including treatment specificity and undesired side effects. To address these, a Dox-loaded Chol-aptamer molecular hybrid (Dox-CAH) was developed. This multivalent interaction system combines the key function of each integrated species: doxorubicin, cholesterol, and two aptamers binding to nucleolin and platelet-derived growth factor BB (PDGF-BB). The study has four stages: preparation of CAH via oligonucleotide hybridization, intercalation of doxorubicin into CAH, verification of CAH binding on SW480 by fluorescence microscopy and flow cytometry, and investigation of effect of Dox-CAH on SW480 proliferation. CAH was successfully prepared, as confirmed by electrophoresis. Flow cytometry and fluorescence microscopy demonstrated CAH binding to SW480, due to the presence of the AS1411 aptamer. This molecular hybrid exhibited specific binding because it did not bind to CCD 841 CoN. CAH binding to PDGF-BB compromises its function, as shown by enzymelinked immunosorbent assay (ELISA) and cell assay. The DNA duplex in this molecular hybrid reduces the cytotoxicity of the Dox-CAH. Binding and the reduction of Dox-CAH toxicity may improve treatment specificity and minimize side effects. Dox-CAH is a model for more effective anticancer therapy, allowing incorporation of chemotherapeutic drugs and recognition elements.

Multifunctional molecular hybrid for targeted colorectal cancer cells: Integrating doxorubicin, AS1411 aptamer, and T9/U4 ASO

“…In the context of Caco-2 cells, upon intercalation of Dox into the DNA duplex of our molecular hybrids, a significant reduction in cytotoxicity was observed. This reduction can be attributed to the DNA duplex system's effectiveness in minimizing the cytotoxic effects of this anti-cancer drug, as previously reported in our study [44]. For SW480 cells, Dox-loaded AS-T9/U4_MH demonstrated the specific delivery of Dox to the cells when compared to the other two control molecular hybrids, as evidenced by the cell viability results.…”

“…The copyright holder for this preprint (which this version posted May 10, 2024. ; https://doi.org/10.1101/2024.05.08.593145 doi: bioRxiv preprint can be attributed to the known ability of AS1411 aptamer to bind to nucleolin, which is overexpressed on the surface of SW480 cells, as reported in the literature [44]. Conversely, the fluorescence images of Caco-2 and CCD841 CoN cells exhibited lower intensity, suggesting less binding of the FAM-labeled AS-T9/U4_MH.…”

“…The fluorescence images revealed that FAM-labeled AS-T9/U4_MH specifically bound to SW480 cells. This specificity 10 can be attributed to the known ability of AS1411 aptamer to bind to nucleolin, which is overexpressed on the surface of SW480 cells, as reported in the literature [44]…”

“…The design of AS1411 aptamer (AS) and T9/U4 antisense oligonucleotide (T9/4U) sequences included additional oligonucleotides to facilitate hybridization with a hybridization strand (HBS). This was achieved by incubating HBS, T9/U4, and AS in a PBS solution at room temperature for their study [44].…”

Progress in cancer drug delivery based on AS1411 oriented nanomaterials

“…The specific process is shown in Fig. 16 A. Pichayanoot Rotkrua group [ 259 ] developed a Dox-loaded Chol–aptamer molecular hybrid (Dox-CAH) loaded with doxorubicin, cholesterol and nucleolar protein and platelets-derived growth factor BB (PDGF-BB), as shown in Fig. 16 B. CAH showed specific binding to SW480 due to the presence of AS1411 aptamer.…”