One of the promising novel methods for radical tumor resection at a single-cell level is magneto-mechanical microsurgery (MMM) with magnetic nano- or microdisks modified with cancer-recognizing molecules. A low-frequency alternating magnetic field (AMF) remotely drives and controls the procedure. Here, we present characterization and application of magnetic nanodisks (MNDs) as a surgical instrument (“smart nanoscalpel”) at a single-cell level. MNDs with a quasi-dipole three-layer structure (Au/Ni/Au) and DNA aptamer AS42 (AS42-MNDs) on the surface converted magnetic moment into mechanical and destroyed tumor cells. The effectiveness of MMM was analyzed on Ehrlich ascites carcinoma (EAC) cells in vitro and in vivo using sine and square-shaped AMF with frequencies from 1 to 50 Hz with 0.1 to 1 duty-cycle parameters. MMM with the “Nanoscalpel” in a sine-shaped 20 Hz AMF, a rectangular-shaped 10 Hz AMF, and a 0.5 duty cycle was the most effective. A sine-shaped field caused apoptosis, whereas a rectangular-shaped field caused necrosis. Four sessions of MMM with AS42-MNDs significantly reduced the number of cells in the tumor. In contrast, ascites tumors continued to grow in groups of mice and mice treated with MNDs with nonspecific oligonucleotide NO-MND. Thus, applying a “smart nanoscalpel” is practical for the microsurgery of malignant neoplasms.
Background: Glioblastoma remains a challenging brain tumor to treat due to its infiltrative nature. Accurately identifying tumor boundaries during surgery is crucial for successful tumor resection. This study introduces an innovative intraoperative visualization method utilizing a surgical fluorescence microscope to precisely locate tumor cells. The focus of the study is on IR-Glint, a novel preparation comprising Cy7.5-labeled aptamers Gli-233nt and Gli-55_3L specific to human glioblastoma. Methods: The aptamers were modified using molecular modeling and quantum chemical techniques. The effectiveness of the preparation was assessed using flow cytometry and microscopy on primary cultures of human glioblastoma. In vivo studies were conducted on mouse and rabbit models, employing orthotopic xenotransplantation of human brain glioblastoma with various imaging techniques, including PET/CT, in vivo fluorescence visualization, confocal laser scanning, and surgical microscopy. Results: The experiments validated the potential of IR-Glint for intraoperative visualization of glioblastoma using infrared imaging. Surface application of the aptamer-based formulation on the brain allowed clear visualization of the tumor, aiding surgeons in tumor resection. This approach also reduces the dosage required and mitigates potential toxic effects on the patient. Conclusions: This study demonstrates the promising potential of using in-frared dye-labeled aptamers for intraoperative visualization of glioblastoma. By improving surgical treatment outcomes in neurosurgery, this novel approach may pave the way for future advancements in the field.
A comprehensive presentation of a variety of biologically sounding properties of genomes is present; chloroplast genomes are used as a biological matter. Triplet frequency composition is the general issue standing behind the properties. Besides, the new alignment-free error-tolerant method of sequences comparison highly efficient for in/del mismatches is present, for transposons search. Triplet frequency dictionaries determined for a genome, or for a part of that latter were studied through various clustering techniques. The interplay between triplet composition and function reveals on tRNA genes unambiguously shows the prevalence of the function encoded in tRNA gene over the phylogeny: the genes gather into the clusters comprising the genes encoding the same amino acid; more exactly, few gene families exhibit fine cluster pattern corresponding the synonymous codons of amino acid. Previously reported symmetry in chloroplast genomes is shown for a set of gymnosperm: that is mirror symmetry, rotational symmetry, and the second Chargaff's parity rule asymmetry. A family of transposons was found in gymnosperm chloroplast genomes. This family is revealed through the novel comparison method based on convolution calculation, for a set of DNA sequences.