Targeted SPION siderophore conjugate loaded with doxorubicin as a theranostic agent for imaging and treatment of colon carcinoma

Recently, the siderophores have opened new horizons in nanomedicine. The current study aimed to design a theranostic platform based on superparamagnetic iron oxide nanoparticles-pyoverdine (SPION/PVD) conjugates bound to MUC1 aptamer (MUC1Apt) and loaded with doxorubicin (DOX) as an anti-cancer agent. The SPION/PVD complex was covalently conjugated to MUC1Apt and loaded with DOX to prepare a targeted drug delivery system (SPION/PVD/MUC1Apt/DOX). The investigation of cellular cytotoxicity and uptake of formulations by MTT and flow cytometry in both MUC1 positive (C26) and MUC1 negative (CHO) cell lines revealed that MUC1Apt could improve both cellular uptake and toxicity in the C26 cell line. The evaluation of tumor-targeting activity by in vivo bio-distribution showed that the targeted formulation could enhance tumor inhibitory growth effect and survival rate in C26 tumor-bearing mice. Furthermore, the potential of synthesized SPION/PVD/MUC1Apt/DOX complex as diagnostic agents was investigated by magnetic resonance imaging (MRI) which improved the contrast of tumor site in MRI. Our findings confirm that aptamer-targeted PVD chelated the SPION as a diagnostic agent and loaded with DOX as a chemotherapeutic drug, would be beneficial as a novel theranostic platform.

Computational design of single-stranded DNA hairpin aptamers immobilized on a biosensor substrate

Aptamer interactions with a surface of attachment are central to the design and performance of aptamer-based biosensors. We have developed a computational modeling approach to study different system designs—including different aptamer-attachment ends, aptamer surface densities, aptamer orientations, and solvent solutions—and applied it to an anti MUC1 aptamer tethered to a silica biosensor substrate. Amongst all the system designs explored, we found that attaching the anti MUC1 aptamer through the 5′ terminal end, in a high surface density configuration, and solvated in a 0.8 M NaCl solution provided the best exposure of the aptamer MUC1 binding regions and resulted in the least amount of aptamer backbone fluctuations. Many of the other designs led to non-functional systems, with the aptamer collapsing onto the surface. The computational approach we have developed and the resulting analysis techniques can be employed for the rational design of aptamer-based biosensors and provide a valuable tool for improving biosensor performance and repeatability.

Detection of breast cancer-derived exosomes using the horseradish peroxidase-mimicking DNAzyme as an aptasensor

A hairpin-like aptasensor combining the specific MUC1 aptamer with a hemin/G-quadruplex is developed for the detection of breast cancer exosomes.