Magnetite Nanoparticles and Spheres for Chemo- and Photothermal Therapy of Hepatocellular Carcinoma in vitro.

INTRODUCTION: We present a multimodal nanoplatforms for the treatment of hepatocellular carcinoma (HCC) in vitro. The nanoplatforms are based on polydopamine (PDA)-coated magnetite nanoparticles (NPs) and spheres (sMAG) with PAMAM dendrimers and functionalized with NHS-PEG-Mal (N-hydroxysuccinimide-polyethylene glycol-maleimide) linker, which allows their functionalization with a folic acid derivative. The nanomaterials bearing a folic acid-targeting moiety show high efficiency in killing cancer cells in the dual chemo- and photothermal therapy (CT-PTT) of the liver cancer cells in comparison to modalities performed separately. MATERIALS AND METHODS: All materials are characterized in detail with transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, zeta potential and magnetic measurements. Also, photothermal properties were determined under irradiation of nanoparticles with laser beam of 2 W/cm2. The nontoxicity of nanoparticles with doxorubicin and without was checked by WST and LIVE/DEAD assay. Those tests were also used to evaluate materials bearing folic acid and anticancer drug in combined chemo- and photothermal therapy of HCC. Further, the generation of reactive oxygen species profile was also evaluated using flow cytometry test. RESULTS: Both NPs and sMAG showed high photothermal properties. Nevertheless, the higher photothermal response was found for magnetic spheres. Materials of concentration above 10 µg/mL reveal that their activity was comparable to free doxorubicin. It is worth highlighting that a functionalized magnetic sphere with DOXO more strongly affected the HepG2 cells than smaller functionalized nanoparticles with DOXO in the performed chemotherapy. This can be attributed to the larger size of particles and a different method of drug distribution. In the further stage, both materials were assessed in combined chemo- and photothermal therapy (CT-PTT) which revealed that magnetic spheres were also more effective in this modality than smaller nanoparticles. CONCLUSION: Here, we present two types of nanomaterials (nanoparticles and spheres) based on polydopamine and PAMAM dendrimers g.5.0 functionalized with NHS-PEG-Mal linker terminated with folic acid for in vitro hepatocellular carcinoma treatment. The obtained materials can serve as efficient agents for dual chemo- and photothermal therapy of HCC. We also proved that PDA-coated magnetic spheres were more efficient in therapies based on near-infrared irradiation because determined cell viabilities for those materials are lower than for the same concentrations of nanomaterials based on small magnetic nanoparticles.

UV cross-linked polyvinylpyrrolidone electrospun fibres as antibacterial surfaces.

Many bacteria become progressively more resistant to antibiotics and it remains a challenging task to control their overall levels. Polymers combined with active biomolecules come to the forefront for the design of antibacterial materials that can address this encounter. In this work, we investigated the photo-crosslinking approach of UV-sensitive benzophenone molecule (BP) with polyvinylpyrrolidone (PVP) polymer within electrospun fibres. The BP and PVP solutions allowed fabricating polymer mats that were subsequently functionalised with antibacterial lysozyme. The physical properties of the crosslinked electrospun fibres were investigated by scanning electron microscopy and atomic force microscopy. The average diameter of the obtained fibres decreased from 290 ± 50 nm to 270 ± 70 nm upon the addition of the crosslinking molecules and then to 240 ± 80 nm and 180 ± 90 nm after subsequent crosslinking reaction at an increasing time: 3 and 5 h, respectively. The peak force quantitative nanomechanical mapping (PF-QNM) indicated the increase of DMT modulus of obtained cross-linked fibres from 4.1 ± 0.8 GPa to 7.2 ± 0.5 GPa. Furthermore, the successful crosslinking reaction of PVP and BP solution into hydrogels was investigated in terms of examining photo-crosslinking mechanism and was confirmed by rheology, Raman, Fourier transform infrared and nuclear magnetic resonance. Finally, lysozyme was successfully encapsulated within cross-linked PVP-BP hydrogels and these were successfully electrospun into mats which were found to be as effective antibacterial agents as pure lysozyme molecules. The dissolution rate of photo cross-linked PVP mats was observed to increase in comparison to pure PVP electrospun mats which opened a potential route for their use as antibacterial, on-demand, dissolvable coatings for various biomedical applications.