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Targeting canine mammary tumours via gold nanoparticles functionalized with promising Co(II) and Zn(II) compounds

Publication . Raposo, L. R.; Roma-Rodrigues, C.; Jesus, J.; Martins, Luisa; Pombeiro, Armando; Baptista, P. V.; Fernandes, A. R.

Background: Despite continuous efforts, the treatment of canine cancer has still to deliver effective strategies. For example, traditional chemotherapy with doxorubicin and/or docetaxel does not significantly increase survival in dogs with canine mammary tumors (CMTs). Aims: Evaluate the efficiency of two metal compounds [Zn(DION)2]Cl (TS262, DION = 1,10- phenanthroline-5,6-dione) and [CoCl(H2O)(DION)2][BF4] (TS265) and novel nanovectorizations designed to improve the anti-cancer efficacy of these compounds in a new CMT derived cell line (FR37-CMT). Materials and methods: FR37-CMT cells were exposed to different concentrations of TS262 and TS265 and two new nanoparticle systems and cellular viability was determined. These nanosystems are composed of polyethylene-glycol, bovine-serum-albumin and TS262 or TS265 (NanoTS262 or NanoTS265, respectively). Results: In FR37-CMT, TS262 and TS265 displayed IC50 values well below those displayed by doxorubicin and cisplatin. The nanovectorizations further decreased the IC50 values. Discussion: TS262 and TS265 proved to be effective against FR37-CMT cells and more effective than of doxorubicin and cisplatin. The Nanosystems efficiently delivered the cytotoxic cargo inducing a significant reduction of cell viability in FR37-CMT cell line when compared to the free compounds. Conclusions: TS262 and TS265 are compounds with potential in the treatment of CMTs. NanoTS262 and NanoTS265 demonstrate that such simple nanovectorization via gold nanoparticles shows tremendous potential as anti-cancer formulations, which may easily be expanded to suit other cargo.

2017-12Journal article

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Multifunctional gold-nanoparticles: A nanovectorization tool for the targeted delivery of novel chemotherapeutic agentes

Publication . Fernandes, Alexandra; Jesus, João; Martins, Pedro; Figueiredo, Sara; Rosa, Daniela; Martins, Luisa; Corvo, M. Luísa; Carvalheiro, Manuela; Costa, Pedro M.; Baptista, Pedro

Due to their small size and unique properties, multifunctional nanoparticles arise as versatile delivery systems easily grafted with a vast array of functional moieties, such as anticancer cytotoxic chemotherapeutics and targeting agents. Here, we formulated a multifunctional gold-nanoparticle (AuNP) system composed of a monoclonal antibody against epidermal growth factor receptor (EGFR) (anti-EGFR D-11) for active targeting and a Co(II) coordination compound [CoCl(H2O)(phendione)2][BF4] (phendione = 1,10-phenanthroline-5,6-dione) (TS265) with proven antiproliferative activity towards cancer cells (designated as TargetNanoTS265). The efficacy of this nanoformulation, and the non-targeted counterpart (NanoTS265), were evaluated in vitro using cancer cell models and in vivo using mice xenografts. Compared to the free compound, both nanoformulations (TargetNanoTS265 and NanoTS265) efficiently delivered the cytotoxic cargo in a controlled selective manner due to the active targeting, boosting tumor cytotoxicity. Treatment of HCT116-derived xenografts tumors with TargetNanoTS265 led to 93% tumor reduction. This simple conceptual nanoformulation demonstrates the potential of nanovectorization of chemotherapeutics via simple assembly onto AuNPs of BSA/HAS-drug conjugates that may easily be expanded to suit other cargo of novel compounds that require optimized controlled delivery to cancer target.

2017-01-10Journal article

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Combination of chemotherapy and Au-nanoparticle photothermy in the visible light to tackle doxorubicin resistance in cancer cells

Publication . Pedrosa, Pedro; Mendes, Rita; Cabral, Rita; Martins, Luisa; Baptista, Pedro; Fernandes, Alexandra

Despite great advances in the fight against cancer, traditional chemotherapy has been hindered by the dose dependent adverse side effects that reduce the usable doses for effective therapy. This has been associated to drug resistance in tumor cells that often cause relapse and therapy failure. These drawbacks have been tackled by combining different therapeutic regiments that prevent drug resistance while decreasing the chemotherapy dose required for efficacious ablation of cancer. In fact, new metallic compounds have been in a continuous development to extend the existing chemotherapy arsenal for these combined regimens. Here, we demonstrate that combination of a metallic compound (TS265), previously characterized by our group, with photothermy circumvents cells resistant to Doxorubicin (DOX). We first engendered a colorectal carcinoma cell line (HCT116) highly resistant to DOX, whose viability was diminished after administration of TS265. Cancer cell death was potentiated by challenging these cells with 14 nm spherical gold nanoparticles followed by laser irradiation at 532 nm. The combination of TS265 with photothermy lead to 65% cell death of the DOX resistant cells without impacting healthy cells. These results support the use of combined chemotherapy and photothermy in the visible spectrum as an efficient tool for drug resistant tumors.

2018-07-30Journal article

Open access

Evaluation of cell toxicity and DNA and protein binding of green synthesized silver nanoparticles

Publication . Da Costa Ribeiro, Ana Paula; Anbu, S; Alegria, Elisabete; Fernandes, Alexandra; Baptista, Pedro; Mendes, Rita; Matias, A. S.; Mendes, M.; Guedes Da Silva, M. Fátima C.; Pombeiro, Armando

Silver nanoparticles (AgNPs) were prepared by GREEN chemistry relying on the reduction of AgNO3 by phytochemicals present in black tea extract. AgNPs were fully characterized by transmission electron microscopy (TEM), ultraviolet-visible spectroscopy ((UV-vis)), X-ray diffraction (XRD) and energy dispersive absorption spectroscopy (EDS). The synthesized AgNPs induced a decrease of the cell viability in a dose-dependent manner with a low IC50 (0.5 +/- 0.1 mu M) for an ovarian carcinoma cell line (A2780) compared to primary human fibroblasts (IC50 5.0 +/- 0.1 mu M). The DNA binding capability of CT (calf thymus) DNA was investigated using electronic absorption and fluorescence spectroscopies, circular dichroism and viscosity titration methods. Additionally, the AgNPs strongly quench the intrinsic fluorescence of BSA, as determined by synchronous fluorescence spectra.

2018-05Journal article

Open access

Motility and cell shape roles in the rheology of growing bacteria cultures

Publication . Portela, Raquel; Almeida, Pedro L.; Sobral, Rita; R. Leal, Catarina

Cell shape, size and self-motility appear as determinant intrinsic cell factors in the rheological behavior of living bacterial cultures during the growth process. In this work three different species were considered due to their differences on these intrinsic characteristics: two different strains of Staphylococcus aureus – strain COL and its isogenic cell wall autolysis mutant, RUSAL9 – both non-motile and Escherichia coli and Bacillus subtilis – both presenting intrinsic motility. In situ real-time rheology, was used to characterize the activity of growing bacteria, under steady-shear conditions, in particular the viscosity growth curve was measured, for a constant shear flow rate, presenting for all studied cultures, different and rich flow curves. These complex rheological behaviors are a consequence of two coupled effects: the cell density continuous increase and its changing interacting properties, where cell size and shape and intrinsic motility are major players.

2019-03-01Journal article

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