RESUMO
Triple-negative breast cancer (TNBC) remains a clinical challenge due to molecular, metabolic, and genetic heterogeneity as well as the lack of validated drug targets. Thus, therapies or delivery paradigms are needed. Gold-derived compounds including the FDA-approved drug, auranofin have shown promise as effective anticancer agents against several tumors. To improve the solubility and bioavailability of auranofin, we hypothesized that the nanodelivery of auranofin using biodegradable chitosan modified polyethylene glycol (PEG) nanoparticles (NPs) will enhance anticancer activity against TNBC by comparing the best nanoformulation with the free drug. The selection of the nanoformulation was based on synthesis of various chitosan PEG copolymers via formaldehyde-mediated engraftment of PEG onto chitosan to form [chitosan-g-PEG] copolymer. Furthermore, altered physiochemical properties of the copolymer was based on the formaldehyde ratio towards nanoparticles (CP 1-4 NPs). Following the recruitment of PEG onto the chitosan polymer surface, we explored how this process influenced the stiffness of the nanoparticle using atomic force microscopy (AFM), a factor crucial for in vitro and in vivo studies. Our objective was to ensure the full functionality and inherent properties of chitosan as the parent polymer was maintained without allowing PEG to overshadow chitosan's unique cationic properties while improving solubility in neutral pH. Hence, CP 2 NP was chosen. To demonstrate the efficacy of CP 2 NP as a good delivery carrier for auranofin, we administered a dose of 3 mg/kg of auranofin, in contrast to free auranofin, which was given at 5 mg/kg. In vivo studies revealed the potency of encapsulated auranofin against TNBC cells with a severe necrotic effect following treatment superior to that of free auranofin. In conclusion, chitosan-g-PEG nanoparticles have the potential to be an excellent delivery system for auranofin, increasing its effectiveness and potentially reducing its clinical limitations.
Assuntos
Quitosana , Nanopartículas , Neoplasias de Mama Triplo Negativas , Humanos , Quitosana/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Auranofina/farmacologia , Auranofina/uso terapêutico , Polímeros/química , Polietilenoglicóis/química , Nanopartículas/química , Formaldeído/uso terapêuticoRESUMO
Phosphorene nanoribbons (PNRs) have inspired strong research interests to explore their exciting properties that are associated with the unique two-dimensional (2D) structure of phosphorene as well as the additional quantum confinement of the nanoribbon morphology, providing new materials strategy for electronic and optoelectronic applications. Despite several important properties of PNRs, the production of these structures with narrow widths is still a great challenge. Here, a facile and straightforward approach to synthesize PNRs via an electrochemical process that utilize the anisotropic Na+ diffusion barrier in black phosphorus (BP) along the [001] zigzag direction against the [100] armchair direction, is reported. The produced PNRs display widths of good uniformity (10.3 ± 3.8 nm) observed by high-resolution transmission electron microscopy, and the suppressed B2g vibrational mode from Raman spectroscopy results. More interestingly, when used in field-effect transistors, synthesized bundles exhibit the n-type behavior, which is dramatically different from bulk BP flakes which are p-type. This work provides insights into a new synthesis approach of PNRs with confined widths, paving the way toward the development of phosphorene and other highly anisotropic nanoribbon materials for high-quality electronic applications.