<p>Synergistic Treatment of Tumor by Targeted Biotherapy and Chemotherapy via Site-Specific Anchoring of Aptamers on DNA Nanotubes</p>

Abstract

Background: Aptamers have been widely used as targeted therapeutic agents due to its relatively small physical size, flexible structure, high specificity, and selectivity. Aptamers functionalized nanomaterials, not only enhance the targeting of nanomaterials, but can also improve the stability of the aptamers. We developed aptamer C2NP (Apt) conjugated straight DNA nanotubes (S-DNT-Apt) and twisted DNA nanotubes (T-DNT-Apt) as nanocarriers for doxorubicin (DOX). Methods: The twisted DNA nanotubes (T-DNT) and straight DNA nanotubes (S-DNT) were assembled with a scaffold and hundreds of staples. Apt was site-specifically anchored on DNA nanotubes with either different spatial distribution (3 or 6 nm) or varied stoichiometry (15Apt or 30Apt). The developed nanocarriers were characterized with agarose gel electrophoresis and transmission electron microscopy. The drug loading and release in vitro were evaluated by measuring the fluorescence intensity of DOX using a microplate reader. The stability of DNT in cell culture medium plus 10% of FBS was evaluated by agarose gel electrophoresis. The cytotoxicity of DNA nanostructures against K299 cells was tested with a standard CCK8 method. Cellular uptake, cell apoptosis, cell cycle and reactive oxygen species level were investigated by flow cytometry. The expression of p53 was examined by Western Blot. Results: T-DNT-30Apt-6 exhibited the highest cytotoxicity when the concentration of Apt was 120 nM. After intercalation of DOX, the cytotoxicity of DOX@T-DNT-30Apt-6 was further enhanced due to the combination of chemotherapy of DOX and biotherapy of Apt. The enhanced cytotoxicity of DOX@T-DNT-30Apt-6 can be explained by the increase in the cellular uptake, cell apoptosis and intracellular ROS levels. Additionally, the interaction between Apt and its receptor CD30 could upregulate the expression of p53. Conclusion: These results demonstrate that both stoichiometry and spatial arrangement of Apt on T-DNT-Apt influence the anticancer activity. The developed twisted DNA nanotubes may be a solution for the synergistic treatment of cancer.

Gold–Nickel Nanowires as Nanomotors for Cancer Marker Biodetection and Chemotherapeutic Drug Delivery

“…Also, the concentration-dependent toxicity trend which was higher than nondrug loaded nanomotors was observed in all motor concentrations (>95% viable cells). DOX binds to DNA by intercalation and inhibits nucleic acid synthesis in the cell . Therefore, the cell viability decreases with increasing drug concentration and nanomotor concentration .…”

“…DOX binds to DNA by intercalation and inhibits nucleic acid synthesis in the cell. 31 Therefore, the cell viability decreases with increasing drug concentration and nanomotor concentration. 38 When biocompatibilities of nanomotors are examined, no obvious cytotoxicity was detected until 100 μM DOX (20% nanomotor concentration).…”

“…Furthermore, metal deposition from the Ni target served direct preparation and prevented any other chemical reagent utilization. Then the biomedical applications of these nanowires as nanomotors were performed for an important cancer biomarker miRNA-21 which was used mainly for the diagnosis of solid tumors including mainly breast, colorecteral, prostate, gastric, pancreatic, and lung cancers , and controlled and triggered the release of a commonly used antitumor agent Doxorubicin. , For the biosensing study, the proposed nanomotors provided highly sensitive, selective, and reproducible results for miRNA-21 detection. For the drug delivery approach, improvement in the nanomotor speeds provided controllable changes under implemented factors including NIR triggered and pH-dependent studies.…”

Nucleic Acids for Potential Treatment of Rheumatoid Arthritis

“…Furthermore, some of the aptamers can activate the downstream signaling pathways once binding to their receptors and can thus be used as therapeutics as well. For instance, DNA aptamer SL2B, AS1411, and C2NP have been anchored onto various nanostructures and utilized as therapeutics for cancer treatment. − Inspired by these findings, both therapeutic DNA aptamers and RNA aptamers have also been developed to combat RA (Table ). We classify the therapeutic aptamers based on their targets, and the applications on RA therapy are discussed in this section.…”

Recent Advances and Implication of Bioengineered Nanomaterials in Cancer Theranostics

“…Gadolinium-doped silica nanoparticles have shown a longitudinal relaxation rate. Gadolinium and fluorescent dye named Cy5.5 were used to achieve MRI/fluorescence bimodal imaging [31]. The dye in the NIR region has low autofluorescence interference and high imaging sensitivity, which enables accurate positioning of the probe.…”