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Abstract: Treatment of biologically complex diseases, such as cancer, can significantly benefit from combination therapies. These powerful therapies are able to simultaneously target different biological targets, thereby overcoming or reducing drug resistance, decreasing dose-related toxicity, and potentially exhibiting synergistic effects. Herein, we combine the effects of nitric oxide (NO) gas therapy and an anticancer drug Doxorubicin (Dox) using a porous organic polymer (POP) as a delivery vehicle for both. SH-POP, synthesized by a facile, room-temperature method, is rich in both thiol (-SH) and secondary amine (R-NH-R’) functional groups, which can be post-synthetically nitrosylated in a room-temperature reaction that uses water as a solvent, yielding SNO-POP. Fourier-transform infrared (FT-IR) and Raman spectroscopy confirm that both types of functional groups are nitrosylated. Upon white light irradiation, SNO-POP releases up to ~60 µmol of NO per g, and exhibits reversible switch on – switch off NO release behavior triggered by simple light irradiation for at least 20 cycles. Unlike many conventional systems, where a known small-molecule NO donor is incorporated into the pores, here, the porous polymer itself serves as a NO donor, so the pores remain available for the encapsulation of another therapeutic, i.e. Dox. The release of Dox from the Dox@SNO-POP system is pH-sensitive and occurs preferentially in a slightly acidic environment (pH = 5.4). HeLa cancer cell viability studies confirm an enhancement in toxicity that can be ascribed to the synergistic effects of light-triggered NO release and pH-triggered Dox release. Confocal microscopy imaging reveals the presence of both species inside cells. This study is expected to stimulate the development of porous polymers as potent vehicles for combination therapies in cancer treatment and beyond.
Keywords: porous organic polymer, nitric oxide, combination therapy, synergistic therapy, chemotherapy
Published in RUNG: 05.07.2024; Views: 770; Downloads: 2
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Keywords: calixarene, nanosheets, covalent polymer, iodine adsorption
Published in RUNG: 02.09.2020; Views: 4139; Downloads: 0
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Abstract: The study of an electrochemical synthesis of polymethylsilane from trifunctional trichloro- methylsilane monomers identified a single polymerization pathway involving reduction of the monomer to silyl anions and their addition to the growing polymer. The sizes of the synthesized macromolecules, measured with dynamic light scattering, are much larger than the theoretical size estimated for an ideal dendrimer. The reason for this, found by NMR analysis, is in a large number of branching irregularities (defects) contained in the molecular structure, which can be described as a hyperbranched dendritic polymer. Theoretical estimates of sizes for an ideal dendrimer were corrected assuming a branching defect is a cavity with the volume of one monomer. Appropriateness of the theoretical and experimental models was confirmed with a good quantitative agreement between the experimental densities and the theoretically calculated values.
Keywords: Polymethylsilane Dendritic polymer Electropolymerization
Published in RUNG: 20.03.2017; Views: 5186; Downloads: 19
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Abstract: The design of new strong and selective binders is a key step towards the development of new sensing devices and effective drugs. Both affinity and selectivity can be increased through chelation and here we theoretically explore the possibility of coupling two binders through a flexible linker. We prove the enhanced ability of double binders of keeping their target with a simple model where a polymer composed by hard spheres interacts with a spherical macromolecule, such as a protein, through two sticky spots. By Monte Carlo simulations and thermodynamic integration we show the chelating effect to hold for coupling polymers whose radius of gyration is comparable to size of the chelated particle. We show the binding free energy of flexible double binders to be higher than that of two single binders and to be maximized when the binding sites are at distances comparable to the mean free polymer end-to-end distance. The affinity of two coupled binders is therefore predicted to increase non linearly and in turn, by targeting two non-equivalent binding sites, this will lead to higher selectivity.
Keywords: chelation, polymer, multivalency, bidentate, free energy, thermodynamic integration, Monte Carlo
Published in RUNG: 11.10.2016; Views: 4787; Downloads: 155
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