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Article ; Online: The Transformative Potential of Lipid Nanoparticle-Protein Corona for Next-Generation Vaccines and Therapeutics.

Amici, Augusto / Pozzi, Daniela / Marchini, Cristina / Caracciolo, Giulio

2023 Volume 20, Issue 11, Page(s) 5247–5253

Abstract: The integration of the lipid nanoparticle (LNP)-protein corona as a pioneering approach for the development of vaccines against the present and future SARS-CoV-2 variants of concern marks a significant shift in the field. This concept holds great promise, ...

Abstract	The integration of the lipid nanoparticle (LNP)-protein corona as a pioneering approach for the development of vaccines against the present and future SARS-CoV-2 variants of concern marks a significant shift in the field. This concept holds great promise, offering a universal platform that can be adaptable to combat future pandemics caused by unknown viruses. Understanding the complex interactions among the protein corona, LNPs, and receptors is crucial for harnessing its potential. This knowledge will allow optimal vaccine formulations and improve their effectiveness. Safety assessments are essential to ensure suitability for human use, compliance with regulatory standards, and rigorous quality control in manufacturing. This transformative workflow requires collaborative efforts, expanding our foundational knowledge and translating advancements from the laboratory to clinical reality. The LNP-protein corona approach represents a paradigmatic shift with far-reaching implications. Its principles and insights can be leveraged beyond specific applications against SARS-CoV-2, enabling a universal platform for addressing viral threats, cancer, and genetic diseases.
MeSH term(s)	Humans ; Protein Corona ; Liposomes ; Pandemics/prevention & control ; Vaccines
Chemical Substances	Lipid Nanoparticles ; Protein Corona ; Liposomes ; Vaccines
Language	English
Publishing date	2023-10-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2138405-8
ISSN	1543-8392 ; 1543-8384
ISSN (online)	1543-8392
ISSN	1543-8384
DOI	10.1021/acs.molpharmaceut.3c00479
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Article ; Online: Insights into the effect of polyethylene terephthalate (PET) microplastics on HER2 signaling pathways.

Cui, Lishan / Digiacomo, Luca / Xiao, Siyao / Wang, Junbiao / Amici, Augusto / Pozzi, Daniela / Caracciolo, Giulio / Marchini, Cristina

Toxicology in vitro : an international journal published in association with BIBRA

2023 Volume 91, Page(s) 105632

Abstract: Plastic pollution poses a significant threat to both ecosystems and human health, as fragments of microscale size are daily inhaled and ingested. Such tiny specks are defined as microplastics (MPs), and although their presence as environmental ... ...

Abstract	Plastic pollution poses a significant threat to both ecosystems and human health, as fragments of microscale size are daily inhaled and ingested. Such tiny specks are defined as microplastics (MPs), and although their presence as environmental contaminants is ubiquitous in the world, their possible effects at biological and physiological levels are still not clear. To explore the potential impacts of MP exposure, we produced and characterized polyethylene terephthalate (PET) micro-fragments, then administered them to living cells. PET is widely employed in the production of plastic bottles, and thus represents a potential source of environmental MPs. However, its potential effects on public health are hardly investigated, as the current bio-medical research on MPs mainly utilizes different models, such as polystyrene particles. This study employed cell viability assays and Western blot analysis to demonstrate cell-dependent and dose-dependent cytotoxic effects of PET MPs, as well as a significant impact on HER-2-driven signaling pathways. Our findings provide insight into the biological effects of MP exposure, particularly for a widely used but poorly investigated material such as PET.
MeSH term(s)	Humans ; Microplastics/toxicity ; Plastics/toxicity ; Polyethylene Terephthalates/toxicity ; Ecosystem ; Polystyrenes/toxicity ; Water Pollutants, Chemical/toxicity ; Environmental Monitoring
Chemical Substances	Microplastics ; Plastics ; Polyethylene Terephthalates ; Polystyrenes ; Water Pollutants, Chemical
Language	English
Publishing date	2023-06-15
Publishing country	England
Document type	Journal Article
ZDB-ID	639064-x
ISSN	1879-3177 ; 0887-2333
ISSN (online)	1879-3177
ISSN	0887-2333
DOI	10.1016/j.tiv.2023.105632
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Article ; Online: Breast Cancer Treatment: The Case of Gold(I)-Based Compounds as a Promising Class of Bioactive Molecules.

Galassi, Rossana / Luciani, Lorenzo / Wang, Junbiao / Vincenzetti, Silvia / Cui, Lishan / Amici, Augusto / Pucciarelli, Stefania / Marchini, Cristina

Biomolecules

2022 Volume 12, Issue 1

Abstract: Breast cancers (BCs) may present dramatic diagnoses, both for ineffective therapies and for the limited outcomes in terms of lifespan. For these types of tumors, the search for new drugs is a primary necessity. It is widely recognized that gold compounds ...

Abstract	Breast cancers (BCs) may present dramatic diagnoses, both for ineffective therapies and for the limited outcomes in terms of lifespan. For these types of tumors, the search for new drugs is a primary necessity. It is widely recognized that gold compounds are highly active and extremely potent as anticancer agents against many cancer cell lines. The presence of the metal plays an essential role in the activation of the cytotoxicity of these coordination compounds, whose activity, if restricted to the ligands alone, would be non-existent. On the other hand, gold exhibits a complex biochemistry, substantially variable depending on the chemical environments around the central metal. In this review, the scientific findings of the last 6-7 years on two classes of gold(I) compounds, containing phosphane or carbene ligands, are reviewed. In addition to this class of Au(I) compounds, the recent developments in the application of Auranofin in regards to BCs are reported. Auranofin is a triethylphosphine-thiosugar compound that, being a drug approved by the FDA-therefore extensively studied-is an interesting lead gold compound and a good comparison to understand the activities of structurally related Au(I) compounds.
MeSH term(s)	Antineoplastic Agents/chemistry ; Antineoplastic Agents/therapeutic use ; Auranofin/chemistry ; Auranofin/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Female ; Gold/chemistry ; Gold/therapeutic use ; Humans ; Structure-Activity Relationship
Chemical Substances	Antineoplastic Agents ; Auranofin (3H04W2810V) ; Gold (7440-57-5)
Language	English
Publishing date	2022-01-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12010080
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Article ; Online: SIRT6 promotes metastasis and relapse in HER2-positive breast cancer.

Andreani, Cristina / Bartolacci, Caterina / Persico, Giuseppe / Casciaro, Francesca / Amatori, Stefano / Fanelli, Mirco / Giorgio, Marco / Galié, Mirco / Tomassoni, Daniele / Wang, Junbiao / Zhang, Xiaoting / Bick, Gregory / Coppari, Roberto / Marchini, Cristina / Amici, Augusto

Scientific reports

2023 Volume 13, Issue 1, Page(s) 22000

Abstract: The histone deacetylase sirtuin 6 (SIRT6) has been endowed with anti-cancer capabilities in many tumor types. Here, we investigate the impact of SIRT6-overexpression (SIRT6-OE) in Delta16HER2 mice, which are a bona fide model of HER2-positive breast ... ...

Abstract	The histone deacetylase sirtuin 6 (SIRT6) has been endowed with anti-cancer capabilities in many tumor types. Here, we investigate the impact of SIRT6-overexpression (SIRT6-OE) in Delta16HER2 mice, which are a bona fide model of HER2-positive breast cancer. After an initial delay in the tumor onset, SIRT6-OE induces a more aggressive phenotype of Delta16HER2 tumors promoting the formation of higher number of tumor foci and metastases than controls. This phenotype of SIRT6-OE tumors is associated with cancer stem cell (CSC)-like features and tumor dormancy, and low senescence and oxidative DNA damage. Accordingly, a sub-set of HER2-positive breast cancer patients with concurrent SIRT6-OE has a significant poorer relapse-free survival (RFS) probability than patients with low expression of SIRT6. ChIP-seq, RNA-seq and RT-PCR experiments indicate that SIRT6-OE represses the expression of the T-box transcription factor 3 (Tbx3) by deacetylation of H3K9ac. Accordingly, loss-of-function mutations of TBX3 or low TBX3 expression levels are predictive of poor prognosis in HER2-positive breast cancer patients. Our work indicates that high levels of SIRT6 are indicative of poor prognosis and high risk of metastasis in HER2-positive breast cancer and suggests further investigation of TBX3 as a downstream target of SIRT6 and co-marker of poor-prognosis. Our results point to a breast cancer subtype-specific effect of SIRT6 and warrant future studies dissecting the mechanisms of SIRT6 regulation in different breast cancer subtypes.
MeSH term(s)	Humans ; Animals ; Mice ; Female ; Breast Neoplasms/pathology ; Neoplasm Recurrence, Local ; Sirtuins/metabolism ; Chronic Disease
Chemical Substances	Sirtuins (EC 3.5.1.-) ; SIRT6 protein, human (EC 3.5.1.-)
Language	English
Publishing date	2023-12-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-49199-7
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Article ; Online: Walking a Tightrope: A Perspective of Resveratrol Effects on Breast Cancer.

Bartolacci, Caterina / Andreani, Cristina / Amici, Augusto / Marchini, Cristina

Current protein & peptide science

2017

Abstract: It is an acknowledged fact that health benefits are derived from fruit- and vegetables-enriched diets. In particular, polyphenols, compounds bearing one or more hydroxyl groups attached to an aromatic ring, are ascribed for most of such beneficial ... ...

Abstract	It is an acknowledged fact that health benefits are derived from fruit- and vegetables-enriched diets. In particular, polyphenols, compounds bearing one or more hydroxyl groups attached to an aromatic ring, are ascribed for most of such beneficial effects. Among them, resveratrol, a phytoalexin found in numerous plant species, and more notably in grapes, has widely piqued the interest of the scientific community by virtue of its anti-aging, anti-inflammatory and anti-oxidant properties. Moreover, evidence claiming resveratrol ability to hinder processes underlying all the three steps of carcinogenesis (tumor initiation, progression and metastasization) has propelled an incredibly massive number of studies aimed at enquiring its eventual clinical potential in the fight against cancer. However, despite a large body of data pointing to the advantages of dietary resveratrol intake in respect of certain disease conditions, and cancer inter alia, its real position still remains quite ambiguous. In this uncertain scenario, the present review focuses its attention on the highly entangled relationship between resveratrol and breast cancer, attempting to shape the plethora of controversial results stemming from studies carried out on several in vitro and in vivo breast cancer models. Coping with such a tricky matter, there are so many variabilities concerning both resveratrol itself (dosage, administration, bioavailabilty, among others) and the unique molecular traits of each specific breast cancer subtype that must be taken into account when facing the dilemma: "might resveratrol be protective against breast cancer or does it rather fuel it?"
Language	English
Publishing date	2017-01-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2045662-1
ISSN	1875-5550 ; 1389-2037
ISSN (online)	1875-5550
ISSN	1389-2037
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Article: Multi-Targeted Anticancer Activity of Imidazolate Phosphane Gold(I) Compounds by Inhibition of DHFR and TrxR in Breast Cancer Cells.

Galassi, Rossana / Luciani, Lorenzo / Gambini, Valentina / Vincenzetti, Silvia / Lupidi, Giulio / Amici, Augusto / Marchini, Cristina / Wang, Junbiao / Pucciarelli, Stefania

Frontiers in chemistry

2021 Volume 8, Page(s) 602845

Abstract: A class of phosphane gold(I) compounds, made of azoles and phosphane ligands, was evaluated for a screening on the regards of Breast Cancer cell panels (BC). The compounds possess N-Au-P or Cl-Au-P bonds around the central metal, and they differ for the ... ...

Abstract	A class of phosphane gold(I) compounds, made of azoles and phosphane ligands, was evaluated for a screening on the regards of Breast Cancer cell panels (BC). The compounds possess N-Au-P or Cl-Au-P bonds around the central metal, and they differ for the presence of aprotic or protic polar groups in the azoles and/or the phosphane moieties to tune their hydrophilicity. Among the six candidates, only the compounds having the P-Au-N environment and not displaying neither the hydroxyl nor carboxyl groups in the ligands were found active. The compounds were screened by MTT tests in SKBR3, A17, and MDA-MB231 cancer cells, and two compounds (namely the 4,5-dicyano-imidazolate-1yl-gold(I)-(triphenylphosphane, 5, and 4,5-dichloro-imidazolate-1yl-gold(I)-triphenylphosphane, 6) were found very cytotoxic, with the most active with an IC
Language	English
Publishing date	2021-01-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711776-5
ISSN	2296-2646
ISSN	2296-2646
DOI	10.3389/fchem.2020.602845
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Article: Subcellular Targeting of the

Candelori, Annalisa / Yamamoto, Takaharu G / Iwamoto, Masaaki / Montani, Maura / Amici, Augusto / Vallesi, Adriana

Frontiers in cell and developmental biology

2019 Volume 7, Page(s) 244

Abstract: ... In the ... ...

Abstract	In the ciliate
Language	English
Publishing date	2019-10-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2019.00244
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Article: Efficient Delivery of DNA Using Lipid Nanoparticles.

Cui, Lishan / Renzi, Serena / Quagliarini, Erica / Digiacomo, Luca / Amenitsch, Heinz / Masuelli, Laura / Bei, Roberto / Ferri, Gianmarco / Cardarelli, Francesco / Wang, Junbiao / Amici, Augusto / Pozzi, Daniela / Marchini, Cristina / Caracciolo, Giulio

Pharmaceutics

2022 Volume 14, Issue 8

Abstract: DNA vaccination has been extensively studied as a promising strategy for tumor treatment. Despite the efforts, the therapeutic efficacy of DNA vaccines has been limited by their intrinsic poor cellular internalization. Electroporation, which is based on ... ...

Abstract	DNA vaccination has been extensively studied as a promising strategy for tumor treatment. Despite the efforts, the therapeutic efficacy of DNA vaccines has been limited by their intrinsic poor cellular internalization. Electroporation, which is based on the application of a controlled electric field to enhance DNA penetration into cells, has been the method of choice to produce acceptable levels of gene transfer in vivo. However, this method may cause cell damage or rupture, non-specific targeting, and even degradation of pDNA. Skin irritation, muscle contractions, pain, alterations in skin structure, and irreversible cell damage have been frequently reported. To overcome these limitations, in this work, we use a microfluidic platform to generate DNA-loaded lipid nanoparticles (LNPs) which are then characterized by a combination of dynamic light scattering (DLS), synchrotron small-angle X-ray scattering (SAXS), and transmission electron microscopy (TEM). Despite the clinical successes obtained by LNPs for mRNA and siRNA delivery, little is known about LNPs encapsulating bulkier DNA molecules, the clinical application of which remains challenging. For in vitro screening, LNPs were administered to human embryonic kidney 293 (HEK-293) and Chinese hamster ovary (CHO) cell lines and ranked for their transfection efficiency (TE) and cytotoxicity. The LNP formulation exhibiting the highest TE and the lowest cytotoxicity was then tested for the delivery of the DNA vaccine pVAX-hECTM targeting the human neoantigen HER2, an oncoprotein overexpressed in several cancer types. Using fluorescence-activated cell sorting (FACS), immunofluorescence assays and fluorescence confocal microscopy (FCS), we proved that pVAX-hECTM-loaded LNPs produce massive expression of the HER2 antigen on the cell membrane of HEK-293 cells. Our results provide new insights into the structure-activity relationship of DNA-loaded LNPs and pave the way for the access of this gene delivery technology to preclinical studies.
Language	English
Publishing date	2022-08-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics14081698
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Article ; Online: The protein corona reduces the anticancer effect of graphene oxide in HER-2-positive cancer cells.

Cui, Lishan / Quagliarini, Erica / Xiao, Siyao / Giulimondi, Francesca / Renzi, Serena / Digiacomo, Luca / Caracciolo, Giulio / Wang, Junbiao / Amici, Augusto / Marchini, Cristina / Pozzi, Daniela

Nanoscale advances

2022 Volume 4, Issue 18, Page(s) 4009–4015

Abstract: In the last decade, graphene oxide (GO)-based nanomaterials have attracted much attention for their potential anti-cancer properties against various cancer cell types. However, ... ...

Abstract	In the last decade, graphene oxide (GO)-based nanomaterials have attracted much attention for their potential anti-cancer properties against various cancer cell types. However, while
Language	English
Publishing date	2022-08-24
Publishing country	England
Document type	Journal Article
ISSN	2516-0230
ISSN (online)	2516-0230
DOI	10.1039/d2na00308b
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Article ; Online: Cationic lipid/DNA complexes manufactured by microfluidics and bulk self-assembly exhibit different transfection behavior.

Digiacomo, Luca / Palchetti, Sara / Pozzi, Daniela / Amici, Augusto / Caracciolo, Giulio / Marchini, Cristina

Biochemical and biophysical research communications

2018 Volume 503, Issue 2, Page(s) 508–512

Abstract: Recent advances in biochemical and biophysical research have been achieved through the employment of microfluidic devices. Microfluidic mixing of therapeutic agents with biomaterials yields systems with finely tuned physical-chemical properties for ... ...

Abstract	Recent advances in biochemical and biophysical research have been achieved through the employment of microfluidic devices. Microfluidic mixing of therapeutic agents with biomaterials yields systems with finely tuned physical-chemical properties for applications in drug and gene delivery. Here, we investigate the role of preparation technology (microfluidic mixing vs. bulk self-assembly) on the transfection efficiency (TE) and cytotoxicity of multicomponent cationic liposome/DNA complexes (lipoplexes) in live Chinese hamster ovarian (CHO) cells. Decoupling TE and cytotoxicity allowed us to combine them in a unique coherent vision. While bulk self-assembly produces highly efficient and highly toxic MC lipoplexes, microfluidics manufacture leads to less efficient, but less cytotoxic complexes. This discrepancy is ascribed to two main factors controlling lipid-mediated cell transfection, i.e. the lipoplex concentration at the cell surface and the lipoplex arrangement at the nanoscale. Further research is required to optimize microfluidic manufacturing of lipoplexes to obtain highly efficient and not cytotoxic gene delivery systems.
MeSH term(s)	Animals ; CHO Cells ; Cations/chemistry ; Cricetulus ; DNA/administration & dosage ; DNA/chemistry ; DNA/genetics ; Equipment Design ; Lab-On-A-Chip Devices ; Lipids/chemistry ; Liposomes/chemistry ; Transfection/methods
Chemical Substances	Cations ; Lipids ; Liposomes ; DNA (9007-49-2)
Language	English
Publishing date	2018-06-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2018.05.016
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