Publications by authors named "Marta Canta"

9 Publications

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The investigation of the parameters affecting the ZnO nanoparticle cytotoxicity behaviour: a tutorial review.

Biomater Sci 2020 Nov 20;8(22):6157-6174. Epub 2020 Oct 20.

Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin, Italy.

In the last 30 years the research about zinc oxide nanoparticles (ZnO NPs) and their related toxicity has shown a boom. ZnO NPs show cytotoxicity for both prokaryotic and eukaryotic cells and many studies demonstrated their selective toxicity towards cancer cells. However, with the increasing number of publications, it is observed an increase in the discrepancies obtained between the various results. Soon the scientific community understood that the ZnO NC toxicity behaviour is affected by many factors, related not only to the ZnO NPs themselves, but also to the experimental conditions used. Many recent reviews discussed these parameters by reporting experimental evidence and tried to assess the general statements about the ZnO NP cytotoxicity. This information is extremely useful for the evaluation of which type of ZnO NPs is more or less suitable for a specific study or application. However, despite that, a deep comprehension of the ZnO NP behaviour in relation to the different experimental conditions is still lacking. Actually, a full understanding of the reasons behind the NP behaviour is essential to better assess their biological activity and in particular their therapeutic application, avoiding undesired effects both in the experimental and clinical contexts. This tutorial review aims to be an experimental and practical guide for scientists that faced with the use of ZnO NPs for biomedical applications and, in particular, for their therapeutic purposes. The driving idea is to not simply summarize the results reported in the literature, but to provide instruments for a deep comprehension of the mechanisms affecting the ZnO NP cytotoxicity and behavior. This review also aims to point out the critical experimental parameters to be considered when working with these NPs, as well as the main related risks and limitations that scientists have to face.
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http://dx.doi.org/10.1039/d0bm01086cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610635PMC
November 2020

EVs and Bioengineering: From Cellular Products to Engineered Nanomachines.

Int J Mol Sci 2020 Aug 22;21(17). Epub 2020 Aug 22.

Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin, Italy.

Extracellular vesicles (EVs) are natural carriers produced by many different cell types that have a plethora of functions and roles that are still under discovery. This review aims to be a compendium on the current advancement in terms of EV modifications and re-engineering, as well as their potential use in nanomedicine. In particular, the latest advancements on artificial EVs are discussed, with these being the frontier of nanomedicine-based therapeutics. The first part of this review gives an overview of the EVs naturally produced by cells and their extraction methods, focusing on the possibility to use them to carry desired cargo. The main issues for the production of the EV-based carriers are addressed, and several examples of the techniques used to upload the cargo are provided. The second part focuses on the engineered EVs, obtained through surface modification, both using direct and indirect methods, i.e., engineering of the parental cells. Several examples of the current literature are proposed to show the broad variety of engineered EVs produced thus far. In particular, we also report the possibility to engineer the parental cells to produce cargo-loaded EVs or EVs displaying specific surface markers. The third and last part focuses on the most recent advancements based on synthetic and chimeric EVs and the methods for their production. Both top-down or bottom-up techniques are analyzed, with many examples of applications.
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http://dx.doi.org/10.3390/ijms21176048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504061PMC
August 2020

Zinc Oxide Nanocrystals and High-Energy Shock Waves: A New Synergy for the Treatment of Cancer Cells.

Front Bioeng Biotechnol 2020 5;8:577. Epub 2020 Jun 5.

Department of Applied Science and Technology, Politecnico di Torino, Turin, Italy.

In the last years, different nanotools have been developed to fight cancer cells. They could be administered alone, exploiting their intrinsic toxicity, or remotely activated to achieve cell death. In the latter case, ultrasound (US) has been recently proposed to stimulate some nanomaterials because of the US outstanding property of deep tissue penetration and the possibility of focusing. In this study, for the first time, we report on the highly efficient killing capability of amino-propyl functionalized ZnO nanocrystals (ZnO NCs) in synergy with high-energy ultrasound shock waves (SW) for the treatment of cancer cells. The cytotoxicity and internalization of ZnO NCs were evaluated in cervical adenocarcinoma KB cells, as well as the safety of the SW treatment alone. Then, the remarkably high cytotoxic combination of ZnO NCs and SW was demonstrated, comparing the effect of multiple (3 times/day) SW treatments toward a single one, highlighting that multiple treatments are necessary to achieve efficient cell death. At last, preliminary tests to understand the mechanism of the observed synergistic effect were carried out, correlating the nanomaterial surface chemistry to the specific type of stimulus used. The obtained results can thus pave the way for a novel nanomedicine treatment, based on the synergistic effect of nanocrystals combined with highly intense mechanical pressure waves, offering high efficiency, deep and focused tissue penetration, and a reduction of side effects on healthy cells.
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http://dx.doi.org/10.3389/fbioe.2020.00577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289924PMC
June 2020

ZnO nanocrystals shuttled by extracellular vesicles as effective Trojan nano-horses against cancer cells.

Nanomedicine (Lond) 2019 11 21;14(21):2815-2833. Epub 2019 Nov 21.

Department of Applied Science & Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin, Italy.

The effective application of nanoparticles in cancer theranostics is jeopardized by their aggregation in biological media, rapid degradation and clearance. The design of biomimetic nanoconstructs with enhanced colloidal stability and non-immunogenicity is therefore essential. We propose naturally stable cell-derived extracellular vesicles to encapsulate zinc oxide (ZnO) nanocrystals as efficacious nanodrugs, to obtain highly biomimetic and stable Trojan nano-horses (TNHs). Coupling efficiency, biostability, cellular cytotoxicity and internalization were tested. studies showed a high internalization of TNHs into cancer cells and efficient cytotoxic activity thanks to ZnO intracellular release. TNHs represent an efficient biomimetic platform for future nanotheranostic applications, with biomimetic extracellular vesicle-lipid envelope, facilitated ZnO cellular uptake and potential therapeutic implications.
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http://dx.doi.org/10.2217/nnm-2019-0231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610546PMC
November 2019

Improving dispersal of therapeutic nanoparticles in the human body.

Nanomedicine (Lond) 2019 04 21;14(7):797-801. Epub 2019 Mar 21.

Department of Applied Science & Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, Torino 10129, Italy.

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http://dx.doi.org/10.2217/nnm-2019-0070DOI Listing
April 2019

Nanoparticle-assisted ultrasound: A special focus on sonodynamic therapy against cancer.

Chem Eng J 2018 May;340:155-172

Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin, Italy.

At present, ultrasound radiation is broadly employed in medicine for both diagnostic and therapeutic purposes at various frequencies and intensities. In this review article, we focus on therapeutically-active nanoparticles (NPs) when stimulated by ultrasound. We first introduce the different ultrasound-based therapies with special attention to the techniques involved in the oncological field, then we summarize the different NPs used, ranging from soft materials, like liposomes or micro/nano-bubbles, to metal and metal oxide NPs. We therefore focus on the sonodynamic therapy and on the possible working mechanisms under debate of NPs-assisted sonodynamic treatments. We support the idea that various, complex and synergistics physical-chemical processes take place during acoustic cavitation and NP activation. Different mechanisms are therefore responsible for the final cancer cell death and strongly depends not only on the type and structure of NPs or nanocarriers, but also on the way they interact with the ultrasonic pressure waves. We conclude with a brief overview of the clinical applications of the various ultrasound therapies and the related use of NPs-assisted ultrasound in clinics, showing that this very innovative and promising approach is however still at its infancy in the clinical cancer treatment.
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http://dx.doi.org/10.1016/j.cej.2018.01.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420022PMC
May 2018

A Microwave-Assisted Synthesis of Zinc Oxide Nanocrystals Finely Tuned for Biological Applications.

Nanomaterials (Basel) 2019 Feb 6;9(2). Epub 2019 Feb 6.

Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin, Italy.

Herein we report a novel, easy, fast and reliable microwave-assisted synthesis procedure for the preparation of colloidal zinc oxide nanocrystals (ZnO NCs) optimized for biological applications. ZnO NCs are also prepared by a conventional solvo-thermal approach and the properties of the two families of NCs are compared and discussed. All of the NCs are fully characterized in terms of morphological analysis, crystalline structure, chemical composition and optical properties, both as pristine nanomaterials or after amino-propyl group functionalization. Compared to the conventional approach, the novel microwave-derived ZnO NCs demonstrate outstanding colloidal stability in ethanol and water with long shelf-life. Furthermore, together with their more uniform size, shape and chemical surface properties, this long-term colloidal stability also contributes to the highly reproducible data in terms of biocompatibility. Actually, a significantly different biological behavior of the microwave-synthesized ZnO NCs is reported with respect to NCs prepared by the conventional synthesis procedure. In particular, consistent cytotoxicity and highly reproducible cell uptake toward KB cancer cells are measured with the use of microwave-synthesized ZnO NCs, in contrast to the non-reproducible and scattered data obtained with the conventionally-synthesized ones. Thus, we demonstrate how the synthetic route and, as a consequence, the control over all the nanomaterial properties are prominent points to be considered when dealing with the biological world for the achievement of reproducible and reliable results, and how the use of commercially-available and under-characterized nanomaterials should be discouraged in this view.
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http://dx.doi.org/10.3390/nano9020212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410313PMC
February 2019

PARP1 expression drives the synergistic antitumor activity of trabectedin and PARP1 inhibitors in sarcoma preclinical models.

Mol Cancer 2017 04 28;16(1):86. Epub 2017 Apr 28.

Sarcoma Unit, Medical Oncology, Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Torino, Italy.

Background: Enhancing the antitumor activity of the DNA-damaging drugs is an attractive strategy to improve current treatment options. Trabectedin is an isoquinoline alkylating agent with a peculiar mechanism of action. It binds to minor groove of DNA inducing single- and double-strand-breaks. These kinds of damage lead to the activation of PARP1, a first-line enzyme in DNA-damage response pathways. We hypothesized that PARP1 targeting could perpetuate trabectedin-induced DNA damage in tumor cells leading finally to cell death.

Methods: We investigated trabectedin and PARP1 inhibitor synergism in several tumor histotypes both in vitro and in vivo (subcutaneous and orthotopic tumor xenografts in mice). We searched for key determinants of drug synergism by comparative genomic hybridization (aCGH) and gene expression profiling (GEP) and validated their functional role.

Results: Trabectedin activated PARP1 enzyme and the combination with PARP1 inhibitors potentiated DNA damage, cell cycle arrest at G2/M checkpoint and apoptosis, if compared to single agents. Olaparib was the most active PARP1 inhibitor to combine with trabectedin and we confirmed the antitumor and antimetastatic activity of trabectedin/olaparib combination in mice models. However, we observed different degree of trabectedin/olaparib synergism among different cell lines. Namely, in DMR leiomyosarcoma models the combination was significantly more active than single agents, while in SJSA-1 osteosarcoma models no further advantage was obtained if compared to trabectedin alone. aCGH and GEP revealed that key components of DNA-repair pathways were involved in trabectedin/olaparib synergism. In particular, PARP1 expression dictated the degree of the synergism. Indeed, trabectedin/olaparib synergism was increased after PARP1 overexpression and reduced after PARP1 silencing.

Conclusions: PARP1 inhibition potentiated trabectedin activity in a PARP1-dependent manner and PARP1 expression in tumor cells might be a useful predictive biomarker that deserves clinical evaluation.
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http://dx.doi.org/10.1186/s12943-017-0652-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410089PMC
April 2017

The combination of sorafenib and everolimus shows antitumor activity in preclinical models of malignant pleural mesothelioma.

BMC Cancer 2015 May 8;15:374. Epub 2015 May 8.

Department of Molecular Medicine, - Section of Pneumology, Laboratory of Biochemistry & Genetics, University and Fondazione IRCCS Policlinico San Matteo, Pavia, 27100, Italy.

Background: Malignant Pleural Mesothelioma (MPM) is an aggressive tumor arising from mesothelial cells lining the pleural cavities characterized by resistance to standard therapies. Most of the molecular steps responsible for pleural transformation remain unclear; however, several growth factor signaling cascades are known to be altered during MPM onset and progression. Transducers of these pathways, such as PIK3CA-mTOR-AKT, MAPK, and ezrin/radixin/moesin (ERM) could therefore be exploited as possible targets for pharmacological intervention. This study aimed to identify 'druggable' pathways in MPM and to formulate a targeted approach based on the use of commercially available molecules, such as the multikinase inhibitor sorafenib and the mTOR inhibitor everolimus.

Methods: We planned a triple approach based on: i) analysis of immunophenotypes and mutational profiles in a cohort of thoracoscopic MPM samples, ii) in vitro pharmacological assays, ii) in vivo therapeutic approaches on MPM xenografts. No mutations were found in 'hot spot' regions of the mTOR upstream genes (e.g. EGFR, KRAS and PIK3CA).

Results: Phosphorylated mTOR and ERM were specifically overexpressed in the analyzed MPM samples. Sorafenib and everolimus combination was effective in mTOR and ERM blockade; exerted synergistic effects on the inhibition of MPM cell proliferation; triggered ROS production and consequent AMPK-p38 mediated-apoptosis. The antitumor activity was displayed when orally administered to MPM-bearing NOD/SCID mice.

Conclusions: ERM and mTOR pathways are activated in MPM and 'druggable' by a combination of sorafenib and everolimus. Combination therapy is a promising therapeutic strategy against MPM.
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http://dx.doi.org/10.1186/s12885-015-1363-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429519PMC
May 2015