Targeted Delivery of Chemotherapy Agents Using a Liver Cancer-Specific Aptamer

Abstract

BackgroundUsing antibody/aptamer-drug conjugates can be a promising method for decreasing toxicity, while increasing the efficiency of chemotherapy.Methodology/Principal FindingsIn this study, the antitumor agent Doxorubicin (Dox) was incorporated into the modified DNA aptamer TLS11a-GC, which specifically targets LH86, a human hepatocellular carcinoma cell line. Cell viability tests demonstrated that the TLS11a-GC-Dox conjugates exhibited both potency and target specificity. Importantly, intercalating Dox into the modified aptamer inhibited nonspecific uptake of membrane-permeable Dox to the non-target cell line. Since the conjugates are selective for cells that express higher amounts of target proteins, both criteria noted above are met, making TLS11a-GC-Dox conjugates potential candidates for targeted delivery to liver cancer cells.Conclusions/SignificanceConsidering the large number of available aptamers that have specific targets for a wide variety of cancer cells, this novel aptamer-drug intercalation method will have promising implications for chemotherapeutics in general.

Self-assembled, aptamer-tethered DNA nanotrains for targeted transport of molecular drugs in cancer theranostics

“…Several widely-used anthracycline anticancer drugs, including doxorubicin (Dox), daunorubicin (DNR), and epirubicin (EPR), were used as drug cargo models. Because it is well known that these drugs can preferentially intercalate into double-stranded 5′-GC-3′ or 5′-CG-3′, resulting in the quenching of drug fluorescence (fluorescence "OFF") (20,27,36), M1 and M2 were designed such that all their sequences would form drug intercalation sites (ACG/CGT) in nanotrains, with each pair of M1 and M2 contributing an average of 16 sites. Consequently, each individual nanotrain needs only one aptamer locomotive for targeting, whereas all of the remaining dsDNA "boxcars," as characterized above, are used to carry a high payload of drugs, thus reducing the amount of DNA otherwise required to transport a specific amount of drugs.…”

“…injections every other day: (i) sgc8-NTrs, (ii) free Dox, and (iii) sgc8-NTr-Dox. The Dox dosage was kept the same in groups i and ii at 2 mg/kg, which has been reported for use in this mouse strain (27), and the aptNTr dosage in group i was accordingly maintained the same to that in group iii. Tumor size and body weight were monitored every other day.…”

“…Recent biotechnological advancements have led to a variety of targeted drug transport (TDT) strategies based on aptamer-drug conjugates or aptamer-nanomaterial assemblies (11,12,(18)(19)(20)(21)27). However, these strategies have unique limitations that could hamper the transition to clinical application, including (i) complicated design, laborious and uneconomical bulky preparation of myriad ssDNA as building blocks to construct sophisticated nucleic acid-based nanomaterials, or laborious and inefficient preparation of aptamer-drug conjugates (9,11,14,15,17,18); (ii) limited drug payload capacity and the attendant high cost, hampering production scale-up (9,11,14,15,17,18,20,27); (iii) poor biodegradability, causing chronic accumulation of nanomaterials in vivo (28,29); and (iv) limited universality by the requirement of specific aptamer for drug loading (20).…”

Development and Characterization of a ssDNA-based Aptamer that Selectively Targets Epithelial Carcinoma Cells

“…Briefly, 1 × 105 cells were incubated with Cy3-labeled aptamers (Integrated DNA Technologies) for 30 min at room temperature, washed with PBS, and analyzed by the LSRII flow cytometer (BD Biosciences). Aptamer binding affinity was calculated using the reference method described previously [20,39]. The fluorescent ligand equilibrium dissociation constant (Kd) was obtained by fitting the specific intensity (Y) versus the aptamer concentration (X) plot to the Y=BmaxX/ (Kd +X) equation using SigmaPlot (Jandel, San Rafael, CA).…”

Inhibitory Effect of Chitosan Oligosaccharide on Human Hepatoma Cells in Vitro

“…More than 700,000 new cases are diagnosed throughout the world and more than 600,000 deaths are due to hepatoma each year (Renumathy et al, 2012). Conservative chemotherapy is not efficient for hepatoma patients because of drug resistance and toxic side effects (Meng et al, 2012). Therefore, it is urgent to find a novel therapeutic drug.…”