Aptamer-based approaches are very promising tools in nanomedicine. These small single-stranded DNA or RNA molecules are often used for the effective delivery and increasing biocompatibility of various therapeutic agents. Recently, magnetic nanoparticles (MNPs) have begun to be successfully applied in various fields of biomedicine. The use of MNPs is limited by their potential toxicity, which depends on their biocompatibility. The functionalization of MNPs by ligands increases biocompatibility by changing the charge and shape of MNPs, preventing opsonization, increasing the circulation time of MNPs in the blood, thus shielding iron ions and leading to the accumulation of MNPs only in the necessary organs. Among various ligands, aptamers, which are synthetic analogs of antibodies, turned out to be the most promising for the functionalization of MNPs. This review describes the factors that determine MNPs’ biocompatibility and affect their circulation time in the bloodstream, biodistribution in organs and tissues, and biodegradation. The work also covers the role of the aptamers in increasing MNPs’ biocompatibility and reducing toxicity.
Enzymatic luminescent systems are a promising tool for rapid detection of heavy metals ions for water quality assessment. Nevertheless, their widespread use is limited by the lack of test procedure automation and available sensitive handheld luminometers. Herein we describe integration of disposable microfluidic chips for bioluminescent enzyme-inhibition based assay with a handheld luminometer, which detection system is based on a thermally stabilized silicon photomultiplier (SiPM). Microfluidic chips were made of poly(methyl methacrylate) by micro-milling method and sealed using a solvent bonding technique. The composition of the bioluminescent system in microfluidic chip was optimized to achieve higher luminescence intensity and storage time. Results indicate that developed device provided comparable sensitivity with bench-scale PMT-based commercial luminometers. Limit of detection for copper (II) sulfate reached 2.5 mg/L for developed biosensor. Hereby we proved the concept of handheld enzymatic optical biosensors with disposable chips for bioassay. The proposed biosensor can be used as an early warning field-deployable system for rapid detection of heavy metals salts and other toxic chemicals, which affect bioluminescent signal of enzymatic reaction.
Nanotechnologies involving physical methods of tumor destruction using functional oligonucleotides are promising for targeted cancer therapy. Our study presents magnetodynamic therapy for selective elimination of tumor cells in vivo using DNA aptamer-functionalized magnetic nanoparticles exposed to a low frequency alternating magnetic field. We developed an enhanced targeting approach of cancer cells with aptamers and arabinogalactan. Aptamers to fibronectin (AS-14) and heat shock cognate 71 kDa protein (AS-42) facilitated the delivery of the nanoparticles to Ehrlich carcinoma cells, and arabinogalactan (AG) promoted internalization through asialoglycoprotein receptors. Specific delivery of the aptamer-modified FeAG nanoparticles to the tumor site was confirmed by magnetic resonance imaging (MRI). After the following treatment with a low frequency alternating magnetic field, AS-FeAG caused cancer cell death in vitro and tumor reduction in vivo. Histological analyses showed mechanical disruption of tumor tissues, total necrosis, cell lysis, and disruption of the extracellular matrix. The enhanced targeted magnetic theranostics with the aptamer conjugated superparamagnetic ferroarabinogalactans opens up a new venue for making biocompatible contrasting agents for MRI imaging and performing non-invasive anti-cancer therapies with a deep penetrated magnetic field.
Magnetomechanical therapy is one of the most perspective directions in tumor microsurgery. According to the analysis of recent publications, it can be concluded that a nanoscalpel could become an instrument sufficient for cancer microsurgery. It should possess the following properties: (1) nano- or microsized; (2) affinity and specificity to the targets on tumor cells; (3) remote control. This nano- or microscalpel should include at least two components: (1) a physical nanostructure (particle, disc, plates) with the ability to transform the magnetic moment to mechanical torque; (2) a ligand—a molecule (antibody, aptamer, etc.) allowing the scalpel precisely target tumor cells. Literature analysis revealed that the most suitable nanoscalpel structures are anisotropic, magnetic micro- or nanodiscs with high-saturation magnetization and the absence of remanence, facilitating scalpel remote control via the magnetic field. Additionally, anisotropy enhances the transmigration of the discs to the tumor. To date, four types of magnetic microdiscs have been used for tumor destruction: synthetic antiferromagnetic P-SAF (perpendicular) and SAF (in-plane), vortex Py, and three-layer non-magnetic–ferromagnet–non-magnetic systems with flat quasi-dipole magnetic structures. In the current review, we discuss the biological effects of magnetic discs, the mechanisms of action, and the toxicity in alternating or rotating magnetic fields in vitro and in vivo. Based on the experimental data presented in the literature, we conclude that the targeted and remotely controlled magnetic field nanoscalpel is an effective and safe instrument for cancer therapy or theranostics.
21 October 2021 in Molecular Therapy Nucleic Acids
Identification of primary tumors and metastasis sites is an essential step in cancer diagnostics and the following treatment. Positron emission tomography-computed tomography (PET/CT) is one of the most reliable methods for scanning the whole organism for malignancies. In this work, we synthesized an 11C-labeled oligonucleotide primer and hybridized it to an anti-cancer DNA aptamer. The 11C-aptamer was applied for in vivo imaging of Ehrlich ascites carcinoma and its metastases in mice using PET/CT. The imaging experiments with the 11C-aptamer determined very small primary and secondary tumors of 3 mm2 and less. We also compared 11C imaging with the standard radiotracer, 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG), and found better selectivity of the 11C-aptamer to metastatic lesions in the metabolically active organs than 18F-FDG. 11C radionuclide with an ultra-short (20.38 min) half-life is considered safest for PET/CT imaging and does not cause false-positive results in heart imaging. Its combination with aptamers gives us high-specificity and high-contrast imaging of cancer cells and can be applied for PET/CT-guided drug delivery in cancer therapies.