Despite the growing technological interest of polydopamine (dopamine melanin)-based coatings for a broad variety of applications, the factors governing particle size, shape, and electronic properties of this bioinspired multifunctional material have remained little understood. Herein, we report a detailed characterization of polydopamine growth, particle morphology, and paramagnetic properties as a function of dopamine concentration and nature of the buffer (pH 8.5). Dynamic Light Scattering data revealed an increase in the hydrodynamic radii (Rh) of melanin particles with increasing dopamine concentration in all buffers examined, especially in phosphate buffer. Conversely, a marked inhibition of particle growth was apparent in Tris buffer, with Rh remaining as low as <100 nm during polymerization of 0.5 mM dopamine. Small angle neutron scattering data suggested formation of bidimensional structures in phosphate or bicarbonate buffers, while apparently three-dimensional fractal objects prevailed in Tris buffer. Finally, electron paramagnetic resonance spectra revealed a broader signal amplitude with a peculiar power saturation decay profile for polydopamine samples prepared in Tris buffer, denoting more homogeneous paramagnetic centers with respect to similar samples obtained in phosphate and bicarbonate buffers. Overall, these results disclose Tris buffer as an efficient modulator of polydopamine buildup and properties for the rational control and fine-tuning of melanin aggregate size, morphology, and free radical behavior.
Looking for new metal-based anticancer treatments, in recent years many ruthenium complexes have been proposed as effective and safe potential drugs. In this context we have recently developed a novel approach for the in vivo delivery of Ru(III) complexes, preparing stable ruthenium-based nucleolipidic nanoaggregates endowed with significant antiproliferative activity. Herein we describe the cellular response to our ruthenium-containing formulations in selected models of human breast cancer. By in vitro bioscreens in the context of preclinical studies, we have focused on their ability to inhibit breast cancer cell proliferation by the activation of the intrinsic apoptotic pathway, possibly via mitochondrial perturbations involving Bcl-2 family members and predisposing to programmed cell death. In addition, the most efficient ruthenium-containing cationic nanoaggregates we have hitherto developed are able to elicit both extrinsic and intrinsic apoptosis, as well as autophagy. To limit chemoresistance and counteract uncontrolled proliferation, multiple cell death pathways activation by metal-based chemotherapeutics is a challenging, yet very promising strategy for targeted therapy development in aggressive cancer diseases, such as triple-negative breast cancer with limited treatment options. These outcomes provide valuable, original knowledge on ruthenium-based candidate drugs and new insights for future optimized cancer treatment protocols.
Aiming for novel tools for anticancer therapies, a ruthenium complex, covalently linked to a cholesterol-contg. nucleolipid and stabilized by co-aggregation with a biocompatible lipid, is here presented. The amphiphilic ruthenium complex, named ToThyCholRu, is intrinsically neg. charged and has been inserted into liposomes formed by the cationic 1,2-dioleyl-3-trimethylammoniumpropane chloride (DOTAP) to hinder the degrdn. kinetics typically obsd. for known ruthenium-based antineoplastic agents. The here described nanovectors contain up to 30% in moles of the ruthenium complex and are stable for several weeks. This drug delivery system has been characterized using dynamic light scattering (DLS), small angle neutron scattering (SANS), neutron reflectivity (NR) and ESR techniques. Fluorescence microscopy, following the incorporation of rhodamine-B within the ruthenium-loaded liposomes, showed fast cellular uptake in human carcinoma cells, with a strong fluorescence accumulation within the cells. The in vitro bioactivity profile revealed an important antiproliferative activity and, most remarkably, the highest ability in ruthenium vectorization measured so far. Cellular morphol. changes and DNA fragmentation provided evidence of an apoptosis-inducing activity, in line with several in vitro studies supporting apoptotic events as the main cause for the anticancer properties of ruthenium derivs. Overall, these data highlighted the crucial role played by the cellular uptake properties in detg. the anticancer efficacy of ruthenium-based drugs, showing DOTAP as a very efficient nanocarrier for their stabilization in aq. media and transport in cells. In vitro bioscreens have shown the high antiproliferative activity of ToThyCholRu-DOTAP liposomes against specific human adenocarcinoma cell types. Furthermore, these formulations have proved to be over 20-fold more effective against MCF-7 and WiDr adenocarcinoma cells with respect to the nude ruthenium complex AziRu we have previously described
Inorganic nanoparticles (NPs) exhibit relevant physical properties for application in biomedicine and specifically for both the diagnosis and therapy (i.e. theranostic) of severe pathologies, such as cancer. The inorganic NP core is often not stable in aqueous suspension and can induce cytotoxic effects. For this reason, over the years, several coating strategies were suggested to improve the NP stability in aqueous solutions as well as the NP biocompatibility. Among the various components which can be used for NP coatings, lipids, and in particular phospholipids emerged as versatile molecular building blocks for the production of NP coatings suitable for biomedical application. The recent synthetic efforts in NP lipid coatings allows today to introduce on the NP surface a large variety of lipid molecules eventually in mixture with amphiphilic or hydrophobic drugs or active molecules for cell targeting. In this review, the most relevant examples of NP lipid-coatings are presented and grouped in two main categories: supported lipid bilayers (SLB) and hybrid lipid bilayers (HLB). The discussed scientific cases take into account the most commonly used inorganic NP for biomedical applications in cancer therapy and diagnosis.
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