Search

Functionalized carbon nanotubes (CNTs) have been proposed in the last years as vectors for delivery of biomolecules, proteins and DNA into various cells. In this study, a new multiwalled carbon nanotube β-cyclodextrin platform (MWCNT-CD) modified with branched polyethylenimine (PEI) and doped with Rhodamine (Rhod), MWCNT-CD-PEI-Rhod, was designed and investigated as drug delivery system. The drug binding abilities of MWCNT-CD-PEI-Rhod towards Cidofovir (Cid) and DNA plasmid encoding enhanced green fluorescence protein (pCMS-EGFP) were investigated by complementary spectroscopic techniques. MWCNT-CD-PEI-Rhod showed no significative cytotoxicity and an excellent ability to entrap and delivery Cid. The present study broadens the spectrum of biological evaluation by investigating platform-treatment induced cellular response such as antiviral activity, transfection properties, cellular uptake, internalization mechanisms and cellular localization. The mechanism of cellular uptake was elucidated monitoring the dependence of intracellular red fluorescence from the assembly concentration, time and presence of specific uptake inhibitors. The biological results indicated that MWCNT-CD-PEI-Rhod loaded with Cid and/or pCMS-EGFP crossed the cell membrane via clathrin-dependent pathway and co-localized in lysosomal compartment. However, no green fluorescent protein expression of pCMS-EGFP was detected, whereas the efficient escape of Cid from lysosome and the release close to nuclear region prompted the antiviral activity. [ABSTRACT FROM AUTHOR]

Abstract: The photodynamic activity of a carrier-sensitizer system consisting of heterotopic colloidal nanoparticles (diameter 100–1000nm) of a cationic amphiphilic cyclodextrin, heptakis(2-ω-amino-O-oligo(ethylene oxide)-6-hexylthio)-β-CD (SC6CDNH2) encapsulating the anionic 5,10,15,20-tetrakis(4-sulfonatophenyl)-21H,23H-porphyrin (TPPS) is investigated by an interdisciplinary approach involving the combination of time-resolved absorption and emission techniques with in vitro studies on cultured tumor cells. In a range of TPPS:SC6CDNH2 molar ratios between 1:10 and 1:50 these nanoparticles preserve the photodynamic properties of the entrapped photoactive agent. In fact, the triplet state of TPPS is efficiently populated, very long-lived and, as a consequence, able to produce singlet oxygen (the essential species for the photodynamic action) with quantum yield comparable to the free TPPS. Photodynamic efficacy of the carrier/sensitizer system is proven by in vitro studies on tumor Hela cells treated with TPPS:SC6CDNH2 at different molar ratio, showing significant cells death upon illumination with visible light. [Copyright &y& Elsevier]

The complex trans-bis(dimethylsulfoxide)chloromethylplatinum(II) (1) is fairly soluble in water, where it undergoes multiple equilibria involving the formation of geometrically distinct [Pt(H2O)(DMSO)Cl(CH3)] aqua-species. On reacting an aqueous solution of 1 with monodentate nitrogen donor ligands L, such as pyridines or amines, two well distinct patterns of behavior can be recognized: (i) a single stage fast substitution of one DMSO by the entering ligand, yielding a complex of the type trans(C,N)-[Pt(DMSO)(L)Cl(CH3)] which contains four different groups coordinated to the metal and which undergoes a slow conversion into its cis-isomer, (ii) a double substitution affording cationic complex ions of the type cis-[Pt(L)2(DMSO)(CH3)]+. When this latter reaction is carried out using sterically hindered ligands, slow rotation of the bulk ligand around the Pt–N bond allows for the identification of head-to-head and head-to-tail rotamers in solution, through 1H NMR spectrometry. The addition of chloride anion to 1 leads to the anionic species cis-[Pt(DMSO)Cl2(CH3)]−, where a molecule of DMSO still remains coordinated to the metal center, despite its quite fast rate of ligand exchange (kexch with free DMSO=12±1 s−1). The reaction of complex 1 with bidentate ligands, such as ethylenediamine (en) or simple amino acids, leads to the cationic species [Pt(en)(DMSO)(CH3)]+ or to the neutral [Pt(DMSO)(N–O)(CH3)], (where N–O=GlyO−, AlaO−). [Copyright &y& Elsevier]

Abstract: The aim of this study was to develop nanoparticles made of the amphiphilic cyclodextrin heptakis (2-O-oligo(ethyleneoxide)-6-hexadecylthio-)-β-CD (SC16OH) entrapping docetaxel (Doc) and establish their in vivo potential. Doc-loaded SC16OH nanoparticles were prepared by the emulsion–solvent evaporation technique and fully characterized for size, zeta potential, amount of entrapped drug, release rate and degradation rate. Spherical vesicular nanoparticles displaying a hydrodynamic radius of about 95nm which did not change upon storage as an aqueous dispersion, a negative zeta potential and entrapment efficiency of Doc very close to 100% were produced. DSC study highlighted the crystalline nature of SC16OH, unloaded and Doc-loaded SC16OH nanoparticles which resulted in their very slow dissolution during release stage and well-modulated release of entrapped Doc for about 8 weeks. Doc-loaded SC16OH nanoparticles were not hemolytic toward red blood cells as compared to a commercial Doc formulation (Taxotere®) which shows a dose-dependent toxicity. After exposure of HEp-2 cells to equivalent doses of free Doc and Doc-loaded SC16OH nanoparticles, superior cell killing and cell damage were observed for nanoparticles. Finally, cell damage was attributed to aberrant mitosis which was found to be significantly higher for HEp-2 cells treated with Doc-loaded SC16OH nanoparticles as compared to free Doc likely due to the ability of nanoparticles to slowly release the drug allowing prolonged cell arrest in mitosis. Taken together, these results highlights a great potential of nanoparticles based on SC16OH in solid tumors therapy. [Copyright &y& Elsevier]

Antibacterial agents play a pivotal role in healthcare to prevent contamination of biomedical devices, which can determine infections in surgical and traumatic wound treatments. Furthermore, the COVID-19 pandemic has amplified the importance of protecting common surfaces to avoid bacterial contamination issues. Phenomena such as bacterial resistance push research to develop innovative antibacterial nanosystems. In this context, various agents showing antibacterial properties have appeared, including drug-releasing polymers, organic/inorganic hybrids, and porphyrin derivatives. The silver-based porphyrin derivatives show antibacterial properties despite having some drawbacks, such as toxicity for humans. On the other hand, water-soluble porphyrins, obtained by functionalization of the porphyrin core with PEG chains that enhance solubility and provide stealth properties, have gained attention because of their biocompatibility, structural stability, and tunability. This study focuses on the synthesis and characterization of a PEGylated silver-porphyrin that shows photo-activated antibacterial properties against Pseudomonas aeruginosa and Staphylococcus aureus, antibiotic-resistant pathogens that often coexist and contribute to biofilm-related problems. The porphyrinic system was characterized through NMR, UV–Vis, and fluorescence spectroscopies. Its in-vitro antibacterial activity was investigated and compared with that of the metal-free counterpart. To elucidate the influence of the complexed silver ion and its free base on the photo-antimicrobial effect, the occurrence of demetallation phenomena under irradiation was investigated. The experimental data suggest that the complexation of the silver ion protects the porphyrin core, allowing the photo-bactericidal activity of the system through photo-demetallation phenomena under light irradiation. [Display omitted] • The 5,10, 15, 20-[ p -(ω-methoxy-polyethyleneoxy) phenyl] Ag(II)-porphyrin was synthesized. • Light triggering demetallation of the porphyrin core occurs during photoirradiation. • Different efficacy of the photobactericidal system against Gram positive and negative bacteria. • Redox pathways in the cytoplasmatic environment could induce the demetallation. • The silver into the porphyrin prevents complexation of other common ions in the biological environment. [ABSTRACT FROM AUTHOR]

We describe a mild, ecofriendly, and straightforward two-step strategy for making core-shell Au@Ag bimetallic nanoparticles (BMNPs) for antibacterial nanomedicine and SERS imaging. The synthesis exploits the unique properties of the cationic polymeric cyclodextrin (PolyCD) as both reducing and stabilizing agent to obtain, monodispersed and stable Au@Ag BMNPs. PolyCD-driven protocol includes the synthesis of PolyCD-coated Au monometallic nanoparticles (MNPs) as a seed material for the subsequent growing of a silver shell. PolyCD was produced by polymerization of the azido modified βCD monomers with epichlorohydrin and subsequent reduction of azido derivative. The amino groups, as hydrochloride salts (one for CD ring), are pivotal for the formation of BMNPs in mild conditions. Nanoantibiotics and SERS-nanoTag were prepared by complexation of Au@Ag BMNPs with Linezolid (Lz) and 4-mercaptophenyl boronic acid, respectively. Au@Ag@Lz complexes showed a good antibacterial activity against all tested microorganisms including the methicillin resistant Staphylococcus aureus (MRSA). [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: In analogy to metal nanocomposites, the investigated hybrid organic–inorganic aggregates induce an enhancement of the scattered light. To explain the observed broadening of the absorption band and the wavelength dependence of the scattering, the systems can be considered as a nanoparticle composite. The scattering enhancement obeys the scaling law with the same optical spectral dimension d 0 =0.3 as that obtained through numerical simulations on cluster–cluster aggregates of purely metal nanoparticle composites. [Copyright &y& Elsevier]

Nanoggregates of nonionic amphiphilic cyclodextrin (ACyD) modified with hydrophobic chains of intermediate length [(2-oligo-ethyleneoxide-6-hexylthio)-β-CyD, SC6OH] were prepared by emulsification–diffusion method. They are able to entrap an isoflavone, genistein (Gen), and the complexed species are studied at different host/guest molar ratio. The increased isoflavone solubility in the presence of the aggregates of SC6OH is investigated by UV–Vis spectroscopy, whereas size, charge, and structure of aggregates and their complexes with Gen are measured by means of static and quasi-elastic light scattering, and electrophoretic mobility measurements. On the other hand, preparing samples by the conventional method used for liposomes (hydration of an organic film of SC6OH and sonication) gives rise to aggregates with different sizes and lower colloidal stability. It is shown that the improved stability in water of ACyD aggregates both in the absence and in the presence of Gen, obtained by emulsification–diffusion is due to the existence of nanodomains of organic solvent (RH ≅ 120 nm) which cannot be completely removed by evaporation and freeze-drying and in which host/guest complexes are contained. This result shows that residues of organic solvent from preparation step favor the colloidal stability of the aggregate, but their presence must be taken into account in designing systems for drug delivery. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3141–3149, 2010 [ABSTRACT FROM AUTHOR]

• Development of nanoassemblies based on trade Sulfobutylether-β-cyclodextrin and a cationic porphyrin. • Interaction studies of cyclodextrin and photosensitiser by spectroscopy and optical microscopy. • Elucidation of photodynamic properties of cyclodextrin/photosentiser nanoassemblies. • Sustained release of photosensitiser optimizing antimicrobial photodynamic inactivation of opportunistic bacteria. Nowadays, novel less-expensive nanoformulations for in situ-controlled and safe delivery of photosensitisers (PSs) against opportunistic pathogens in body-infections areas need to be developed. Antimicrobial photodynamic therapy (aPDT) is a promising approach to treat bacterial infections that are recalcitrant to antibiotics. In this paper, we propose the design and characterization of a novel nanophototherapeutic based on the trade cyclodextrin CAPTISOL® (sulfobutylether-beta-cyclodextrin, SBE-βCD) and 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphine tetrakis(p-toluenesulfonate) (TMPyP) to fabricate efficient biocompatible systems for aPDT. Spherical nanoassemblies of about 360 nm based on CAPTISOL®/TMPyP supramolecular complexes with 1:1 stoichiometry and apparent equilibrium binding constant (K b ≅ 1.32 × 105 M−1) were prepared with entrapment efficiency of ≅ 100% by simple mixing in aqueous media and freeze-drying. These systems have been characterized by complementary spectroscopy and microscopy techniques. Time resolved fluorescence pointed out the strong interaction of porphyrin monomer within nanoassemblies (τ 2 ≅ 11 ns with an amount of ca 90%) and scarce self-aggregation of porphyrins have been observed. Singlet oxygen comparative determination (ϕ Δ CAPTISOL ® /TMPyP = 0.58) assessed their photodynamic potential. Release and photostability studies have been carried out under physiological conditions pointing out the role of CAPTISOL® to sustain porphyrin release for more than 2 weeks and to protect PS from photodegradation. Finally, photoantimicrobial activity of nanoassemblies vs free porphyrin have been investigated against Gram-negative P. aeruginosa , E. coli and Gram-positive S. aureus. The proposed nanosystems were able to photokill both Gram-positive and -negative bacterial cells similarly to TMPyP at MBC 90 = 6 µM of TMPyP and at 42 J/cm2 light dose. However, with respect to the less selective free TMPyP in biological sites, nanoassemblies exhibit sustained release properties and a higher photostability thus optimizing the PDT effect at the site of action. These results can open routes for in vivo translational studies on nano(photo)drugs and nanotheranostics based on less expensive formulations of CD and PS. [ABSTRACT FROM AUTHOR]