calix(4)arene and Neoplasms

Tumor selectivity is yet a challenge in chemotherapy-based cancer treatment. A series of calixarenes derivatized at the lower rim with 3-phenyl-1H-pyrazole units with variable upper-rim substituent and conformations of macrocyclic core, alkyl chain length between heterocycle and core, as well as phenolic monomer (5-(4-tert-butylphenyloxy)methoxy-3-phenyl-1H-pyrazole) have been synthesized and characterized in a range of therapeutically relevant cellular models (M-HeLa, MCF7, A-549, PC3, Chang liver, and Wi38) from different target organs/systems. Specific cytotoxicity for M-HeLa cells has been observed in tert-butylcalix[4]arene pyrazoles in 1,3-alternate (compound 7b) and partial cone (compound 7c) conformations with low mutagenicity and haemotoxicity and in vivo toxicity in mice. Compounds 7b,c have induced mitochondrial pathway of apoptosis of M-HeLa cells through caspase-9 activation preceded by the cell cycle arrest at G0/G1 phase. A concomitant overexpression of DNA damage markers in pyrazole-treated M-HeLa cells suggests that calixarene pyrazoles target DNA, which was supported by the presence of interactions between calixarenes and ctDNA at the air-water interface.

Topics: Animals; Calixarenes; HeLa Cells; Humans; Mice; Neoplasms; Porifera; Pyrazoles

Photothermal therapy (PTT) is a method of growing attention, owing to its controllable process, high efficiency and minimal side effect. Indocyanine Green (ICG) is as Food and Drug Administration (FDA) approved agent that stands on the frontline of further developments of PTT toward clinics. However, the applicability of ICG-mediated PTT is limited by the rapid in vivo clearance and photo-degradation of ICG. To improve those parameters, nanosized ICG-loaded nanoparticles (ICG-J/CX) were fabricated in this study by co-assembly of anionic ICG J-aggregates (ICG-J) with cationic tetraguanidinium calix[4]arene (CX). This very simple approach produces ICG-J/CX with a well-defined nanometer range size and a close to neutral charge. The nanoparticles demonstrate high photothermal conversion efficiency (PCE) and dramatically improved photostability, as compared with ICG. The in vitro cellular uptake and cytotoxicity studies further demonstrated that the ICG-J/CX nanoparticles enhance uptake and photothermal efficiency in comparison with ICG or non-formulated ICG-J, overall demonstrating that ICG-J/CX mediated photothermal therapy have significant potential for attaining cancer treatment.

Topics: Animals; Biological Transport; Indocyanine Green; Neoplasms; Photothermal Therapy; Porifera; United States

A new bimodal fluorescent cationic calix[4]arene (L

Topics: Calixarenes; Humans; Luminescent Proteins; Neoplasms; Phenols; Plasmids; Red Fluorescent Protein; Transfection; Water

A novel fluorescently labeled folate conjugate in which four folic acid units are covalently conjugated with a 7-nitro-benzofurazan fluorophore by means of a calix[4]arene platform was synthesized by using a Cu-catalyzed azide-alkyne cycloaddition reaction (click chemistry). The synthesized construct (FA-C4-NBD) was characterized by mass spectrometry, NMR and fluorescence spectroscopy. Confocal fluorescence microscopy experiments were carried out to evaluate the cell penetration ability of FA-C4-NBD on normal and cancer cells. The cellular uptake of FA-C4-NBD proceeds via folate receptor-mediated endocytosis. FA-C4-NBD is internalized into HeLa cancer cells which express high levels of folate receptors, whereas the uptake into fibroblast NIH3T3 cells which have very low expression levels of folate receptors is negligible. The involvement of the folate receptor was corroborated by competition tests with free folic acid. Co-localization analysis with different organelle markers indicated that FA-C4-NBD is not eliminated by recycling towards the outside of the cell, but accumulates intracellularly in the endo-lysosomal system.

Topics: Animals; Calixarenes; Cell Line, Tumor; Drug Design; Fluorescent Dyes; Folic Acid; HeLa Cells; Humans; Mice; Molecular Structure; Neoplasms; NIH 3T3 Cells; Phenols

A novel anticancer vaccine candidate built on a nonpeptidic scaffold has been synthesized. Four S-Tn tumor-associated glycomimetic antigens have been clustered onto a calix[4]arene scaffold bearing an immunoadjuvant moiety (P3CS). The immunogenicity of the synthetic construct has been investigated by immunization of mice in vivo. ELISA assay has evidenced that the tetravalent construct stimulates a higher production of anti-Tn antigen IgG antibodies when compared to an analogous monovalent compound. This result is ascribable to an antigen cluster effect and makes the reported vaccine candidate a good mimic of the natural motifs present on the mucine surface.

Topics: Adjuvants, Immunologic; Animals; Antibodies, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Calixarenes; Cancer Vaccines; Chromatography, Thin Layer; Dipeptides; Enzyme-Linked Immunosorbent Assay; Female; Immunoglobulin G; Immunotherapy; Indicators and Reagents; Lipoproteins; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred BALB C; Molecular Mimicry; Neoplasms; Phenols; Spectrometry, Mass, Electrospray Ionization