ERICA QUAGLIARINI

PhD Graduate

PhD program:: XXXIV


supervisor: Anna Capriotti
advisor: Anna Capriotti

Thesis title: Synthesis and development of multifunctional nanosystems as novel strategies for cancer treatment and diagnosis

We have entered into an era of “The smaller the better”, a key concept that laid the foundations for the increasingly performing development of nanotechnology. This discipline has evolved to such an extent to transform the way medical solutions are developed and delivered through the application in the field of treatments, diagnosis, or prevention of disease. Thus, the term ‘nanomedicine’ is used for the research area which exploits the peculiar properties of nanosystems for the widest clinical applications including mostly nano-based therapies and nano-based diagnostics. The development made in nanotechnologies has provided several advantages including bioavailability, efficacy, dose-response, targeting abilities, personalized medicine, and safety factors. Consequently, the advance of increasingly sophisticated multifunctional nanosystems is of fundamental importance to move from basic research to clinical application. In keeping with these considerations, the following Ph.D. thesis project gives an interesting insight into the various perspectives of nanotechnology in the treatment and diagnosis of different diseases. In fact, during my three-year Ph.D., I focused on the investigation of nanomaterials for the design of innovative and promising nano-based platforms adaptable to three distinct and ever-growing fields of research, namely gene therapy, drug delivery, and cancer diagnosis. Therefore, the main thesis’ skeleton revolves around these three main research topics to which the fourth acts as a link, namely the interaction between nanosystems and biological fluids, an aspect of rare importance and which, by now, cannot be ignored if there is an interest in making your own scientific findings flow into clinical applications. In Chapter 1, some general remarks about the most used nanosystems in medicine, their potential as delivery vectors as well as detection systems, and the effects of the biological environment on their features are exposed with a particular focus on the motivations behind the choice of the two-leading nano-based delivery systems exploited, that are Graphene Oxide (GO) and Lipid Nanoparticles (LNPs). Thus, Chapter 3 is centered on the topic of gene therapy and how GO platforms and LNPs can be efficiently used as gene delivery systems (GDSs). More precisely, starting from an introductory framework on the efficient manufacturing methodology that has been employed for both these two systems, namely the microfluidics, I first exposed the experiments resulting in a hybrid multifunctional GO-based gene delivery platform highly efficient in transfecting a cell model system even more than the gold- standard of lipid-based transfection experiments, that is Lipofectamine 3000. Secondly, I reported the results obtained from the synthesis and in vitro validation of an innovative plasmid DNA (pDNA)-loaded LNP platform. In these last two years, RNA-loaded LNPs are in the spotlight as key constructs of anti-COVID19 vaccine. Nevertheless, the possibility to load pDNA into LNPs has never been explored so far. Our results demonstrated that the synthetic parameters, particularly the microfluidic ones, can be adapted for the specific cargo. This is a noteworthy result, since DNA delivery systems are more handling and versatile than the RNA ones, especially in the fields of vaccination and cancer immunotherapy. Passing from gene delivery to drug delivery, in Chapter 4, I reported our investigation towards the use of a GO platform as an efficient system for the delivery of the chemotherapeutic doxorubicin (DOX) towards cancer cell lines. The results obtained, as well as confirming the versatility that distinguishes this nanomaterial, also demonstrated that GO-DOX complexes exhibit higher anticancer efficacy as compared to Liposomal-DOX, a popular anti-cancer chemotherapy drug. In fact, fluorescence lifetime imaging microscopy indicates that GO-DOX may realize its superior performances by producing huge intracellular DOX release upon binding to the cell membrane. Finally, in the first section of Chapter 5, I showed how the interaction with biological fluids, especially human plasma (HP), allows the formation of an artificial biomolecular layer, the protein corona (PC), that alters the physical-chemical properties and consequently the biological behavior of different nano-based GDSs. Firstly, in light of the preliminary knowledge about the efficiency of our hybrid multifunctional GO-based GDSs, we investigated the bio-nano interactions between these systems and HP providing insight into the transfection behavior of the bio-coronated complexes. Briefly, we demonstrated that a PC formed at high HP concentrations (as those present in in vivo studies) promotes a major capture of the bio-coronated complexes within degradative intracellular compartments (e.g., lysosomes). On the other hand, complexes formed at low protein concentrations lead to high transfection with no appreciable cytotoxicity. This proves that pre-coating of such GO-based GDSs may be a feasible strategy to control their transfection behavior in vivo. Moreover, we investigated the role of the artificial PC on a drug delivery system based on liposomal formulations encapsulating temozolomide (TMZ) a chemotherapy drug that has been shown to improve the average survival rate for people with some high-grade brain tumors. We demonstrated that precoating liposomal TMZ with a PC made of HP proteins can increase the drug penetration in a 3D brain cancer model. The thesis project concludes with the last main topic that is cancer diagnosis. In particular, I reported how we exploited the potential of the PC formation on GO flakes as an advanced diagnostic tool for distinguishing healthy donors from donors affected by two different classes of tumors (Pancreatic Ductal Adenocarcinoma (PDAC) and Glioblastoma (GBM)). The possibility to use PC for cancer detection is derived from the novel concept that PC is personalized or rather influenced by the changes in concentration and structure of individual plasma proteins. I reported three distinct studies based on two different techniques (1D-SDS-PAGE and the magnetic levitation (MagLev)) for the analysis of the PC derived from the oncological patients. Our results demonstrated that PC-based technologies are very effective as detection tools in the field of personalized medicine for cancer diagnosis. The last section, Appendix A, it concerns the experiments under development related to the field of gene delivery and cancer detection. In the first paragraph, I reported the results obtained from the synthesis of an LNP library designed for the delivery of a DNA vaccine effective for the treatment of various cancers. In the second, the last experiments concerning the optimization of the protocols used for the detection of cancer through MagLev device.

Research products

11573/1695929 - 2023 - Inflammatory biomarkers and nanotechnology: new insights in pancreatic cancer early detection
Caputo, Damiano; Quagliarini, Erica; Coppola, Alessandro; La Vaccara, Vincenzo; Marmiroli, Benedetta; Sartori, Barbara; Caracciolo, Giulio; Pozzi, Daniela - 01a Articolo in rivista
paper: INTERNATIONAL JOURNAL OF SURGERY (London : Elsevier London : Surgical Associates Current or last publisher) pp. - - issn: 1743-9159 - wos: WOS:001089168200007 (2) - scopus: (0)

11573/1695927 - 2023 - Stratifying risk for pancreatic cancer by multiplexed blood test
Digiacomo, L.; Quagliarini, E.; Pozzi, D.; Coppola, R.; Caracciolo, G.; Caputo, D. - 01a Articolo in rivista
paper: CANCERS (Basel: MDPI) pp. - - issn: 2072-6694 - wos: WOS:001005171700001 (1) - scopus: 2-s2.0-85161355169 (2)

11573/1695934 - 2023 - Investigating the mechanism of action of DNA-loaded PEGylated lipid nanoparticles
Digiacomo, L.; Renzi, S.; Quagliarini, E.; Pozzi, D.; Amenitsch, H.; Ferri, G.; Pesce, L.; De Lorenzi, V.; Matteoli, G.; Cardarelli, F.; Caracciolo, G. - 01a Articolo in rivista
paper: NANOMEDICINE (New York N.Y.: Elsevier) pp. 102697- - issn: 1549-9642 - wos: WOS:001083110000001 (1) - scopus: 2-s2.0-85167834467 (1)

11573/1671029 - 2023 - Reproducibility of biomolecular corona experiments: a primer for reliable results
Giulimondi, F.; Quagliarini, E.; Digiacomo, L.; Renzi, S.; Palmieri, V.; Papi, M.; Pozzi, D.; Caracciolo, G. - 01a Articolo in rivista
paper: PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION () pp. 1-8 - issn: 1521-4117 - wos: WOS:000897736000001 (0) - scopus: 2-s2.0-85144152145 (0)

11573/1695936 - 2023 - Coupling magnetic levitation of graphene oxide–protein complexes with blood levels of glucose for early detection of pancreatic adenocarcinoma
Quagliarini, E.; Caputo, D.; Cammarata, R.; Caracciolo, G.; Pozzi, D. - 01a Articolo in rivista
paper: CANCER NANOTECHNOLOGY (Wien; New York: Springer) pp. - - issn: 1868-6958 - wos: WOS:000940154100001 (3) - scopus: 2-s2.0-85149249119 (4)

11573/1695931 - 2023 - The influence of protein corona on Graphene Oxide: implications for biomedical theranostics
Quagliarini, E.; Pozzi, D.; Cardarelli, F.; Caracciolo, G. - 01a Articolo in rivista
paper: JOURNAL OF NANOBIOTECHNOLOGY (London : BioMed Central.) pp. 267- - issn: 1477-3155 - wos: WOS:001049202100002 (0) - scopus: 2-s2.0-85167754167 (1)

11573/1659100 - 2022 - Multiplexed detection of pancreatic cancer by combining a nanoparticle-enabled blood test and plasma levels of Acute-Phase Proteins
Caputo, D.; Coppola, A.; Quagliarini, E.; Di Santo, R.; Capriotti, A. L.; Cammarata, R.; Lagana, A.; Papi, M.; Digiacomo, L.; Coppola, R.; Pozzi, D.; Caracciolo, G. - 01a Articolo in rivista
paper: CANCERS (Basel: MDPI) pp. - - issn: 2072-6694 - wos: WOS:000866838700001 (4) - scopus: 2-s2.0-85139835752 (6)

11573/1659049 - 2022 - Nanotechnology Meets Oncology: A Perspective on the Role of the Personalized Nanoparticle-Protein Corona in the Development of Technologies for Pancreatic Cancer Detection
Caputo, D.; Quagliarini, E.; Pozzi, D.; Caracciolo, G. - 01a Articolo in rivista
paper: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. 10591- - issn: 1422-0067 - wos: WOS:000858298300001 (5) - scopus: 2-s2.0-85138703305 (5)

11573/1659101 - 2022 - Efficient delivery of DNA using lipid nanoparticles
Cui, L.; Renzi, S.; Quagliarini, E.; Digiacomo, L.; Amenitsch, H.; Masuelli, L.; Bei, R.; Ferri, G.; Cardarelli, F.; Wang, J.; Amici, A.; Pozzi, D.; Marchini, C.; Caracciolo, G. - 01a Articolo in rivista
paper: PHARMACEUTICS (Basel: MDPI, 2009-) pp. 1-14 - issn: 1999-4923 - wos: WOS:000845673600001 (9) - scopus: 2-s2.0-85137411448 (9)

11573/1659102 - 2022 - 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 - 01a Articolo in rivista
paper: NANOSCALE ADVANCES (Cambridge: Royal Society of Chemistry) pp. 4009-4015 - issn: 2516-0230 - wos: WOS:000847456500001 (6) - scopus: 2-s2.0-85138120150 (6)

11573/1675298 - 2022 - Magnetic Levitation Patterns of Microfluidic-Generated Nanoparticle–Protein Complexes
Digiacomo, L.; Quagliarini, E.; Marmiroli, B.; Sartori, B.; Perini, G.; Papi, M.; Capriotti, A. L.; Montone, C. M.; Cerrato, A.; Caracciolo, G.; Pozzi, D. - 01a Articolo in rivista
paper: NANOMATERIALS (Basel : MDPI) pp. 2376- - issn: 2079-4991 - wos: WOS:000833221300001 (6) - scopus: 2-s2.0-85137371404 (6)

11573/1637729 - 2022 - Magnetic Levitation of Personalized Nanoparticle–Protein Corona as an Effective Tool for Cancer Detection
Quagliarini, E.; Digiacomo, L.; Caputo, D.; Coppola, A.; Amenitsch, H.; Caracciolo, G.; Pozzi, D. - 01a Articolo in rivista
paper: NANOMATERIALS (Basel : MDPI) pp. - - issn: 2079-4991 - wos: WOS:000794837900001 (7) - scopus: 2-s2.0-85128774689 (7)

11573/1659103 - 2022 - A decade of the liposome-protein corona: lessons learned and future breakthroughs in theranostics
Quagliarini, E.; Digiacomo, L.; Renzi, S.; Pozzi, D.; Caracciolo, G. - 01g Articolo di rassegna (Review)
paper: NANO TODAY (Oxford : Elsevier, 2006-) pp. 1-14 - issn: 1748-0132 - wos: WOS:000906892900003 (7) - scopus: 2-s2.0-85140302002 (8)

11573/1671031 - 2022 - Mechanistic insights into the superior DNA delivery efficiency of multicomponent lipid nanoparticles: an in vitro and in vivo study
Quagliarini, E.; Wang, J.; Renzi, S.; Cui, L.; Digiacomo, L.; Ferri, G.; Pesce, L.; De Lorenzi, V.; Matteoli, G.; Amenitsch, H.; Masuelli, L.; Bei, R.; Pozzi, D.; Amici, A.; Cardarelli, F.; Marchini, C.; Caracciolo, G. - 01a Articolo in rivista
paper: ACS APPLIED MATERIALS & INTERFACES (Washington, DC : American Chemical Society) pp. 56666-56677 - issn: 1944-8252 - wos: WOS:000903316900001 (6) - scopus: 2-s2.0-85144461406 (6)

11573/1551429 - 2021 - Protein corona profile of graphene oxide allows detection of glioblastoma multiforme using a simple one-dimensional gel electrophoresis technique. A proof-of-concept study
Di Santo, Riccardo; Quagliarini, Erica; Digiacomo, Luca; Pozzi, Daniela; Di Carlo, Angelina; Caputo, Damiano; Cerrato, Andrea; Montone, Carmela Maria; Mahmoudi, Morteza; Caracciolo, Giulio - 01a Articolo in rivista
paper: BIOMATERIALS SCIENCE (Cambridge : Royal Society of Chemistry, 2013-) pp. 4671-4678 - issn: 2047-4830 - wos: WOS:000652629600001 (7) - scopus: 2-s2.0-85109073960 (11)

11573/1607739 - 2021 - Detection of pancreatic ductal adenocarcinoma by ex vivo magnetic levitation of plasma protein‐coated nanoparticles
Digiacomo, L.; Quagliarini, E.; La Vaccara, V.; Coppola, A.; Coppola, R.; Caputo, D.; Amenitsch, H.; Sartori, B.; Caracciolo, G.; Pozzi, D. - 01a Articolo in rivista
paper: CANCERS (Basel: MDPI) pp. - - issn: 2072-6694 - wos: WOS:000716367300001 (9) - scopus: 2-s2.0-85116990517 (9)

11573/1543148 - 2021 - Inhibiting the growth of 3D brain cancer models with bio-coronated liposomal temozolomide
Perini, Giordano; Giulimondi, Francesca; Palmieri, Valentina; Augello, Alberto; Digiacomo, Luca; Quagliarini, Erica; Pozzi, Daniela; Papi, Massimiliano; Caracciolo, Giulio - 01a Articolo in rivista
paper: PHARMACEUTICS (Basel: MDPI, 2009-) pp. - - issn: 1999-4923 - wos: WOS:000634074300001 (11) - scopus: 2-s2.0-85103125916 (11)

11573/1616584 - 2021 - Microfluidic formulation of DNA-loaded multicomponent lipid nanoparticles for gene delivery
Quagliarini, Erica; Renzi, Serena; Digiacomo, Luca; Giulimondi, Francesca; Sartori, Barbara; Amenitsch, Heinz; Tassinari, Valentina; Masuelli, Laura; Bei, Roberto; Cui, Lishan; Wang, Junbiao; Amici, Augusto; Marchini, Cristina; Pozzi, Daniela; Caracciolo, Giulio - 01a Articolo in rivista
paper: PHARMACEUTICS (Basel: MDPI, 2009-) pp. 1-12 - issn: 1999-4923 - wos: WOS:000689815200001 (23) - scopus: 2-s2.0-85113477946 (21)

11573/1706147 - 2020 - Synergistic analysis of protein corona and haemoglobin levels detects pancreatic cancer
Caputo, D.; Digiacomo, L.; Cascone, C.; Pozzi, D.; Palchetti, S.; Di Santo, R.; Quagliarini, E.; Coppola, R.; Mahmoudi, M.; Caracciolo, G. - 01a Articolo in rivista
paper: CANCERS (Basel: MDPI) pp. 1-11 - issn: 2072-6694 - wos: WOS:000605883600001 (18) - scopus: 2-s2.0-85098883921 (19)

11573/1416248 - 2020 - Personalized graphene oxide-protein corona in the human plasma of pancreatic cancer patients
Di Santo, Riccardo; Digiacomo, Luca; Quagliarini, Erica; Capriotti, Anna Laura; Laganà, Aldo; Zenezini Chiozzi, Riccardo; Caputo, Damiano; Cascone, Chiara; Coppola, Roberto; Pozzi, Daniela; Caracciolo, Giulio - 01a Articolo in rivista
paper: FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY (Lausanne : Frontiers Editorial Office, 2013-) pp. - - issn: 2296-4185 - wos: WOS:000540503800001 (38) - scopus: 2-s2.0-85091417341 (42)

11573/1347196 - 2020 - A comprehensive analysis of liposomal biomolecular corona upon human plasma incubation: the evolution towards the lipid corona
La Barbera, Giorgia; Capriotti, Anna Laura; Caracciolo, Giulio; Cavaliere, Chiara; Cerrato, Andrea; Montone, Carmela Maria; Piovesana, Susy; Pozzi, Daniela; Quagliarini, Erica; Laganà, Aldo - 01a Articolo in rivista
paper: TALANTA (-Oxford, United Kingdom: Elsevier Science Limited Oxford: Pergamon, 1958-) pp. - - issn: 0039-9140 - wos: WOS:000509632900017 (20) - scopus: 2-s2.0-85074463532 (21)

11573/1416238 - 2020 - Effect of protein corona on the transfection efficiency of lipid-coated graphene oxide-based cell transfection reagents
Quagliarini, E.; Di Santo, R.; Palchetti, S.; Ferri, G.; Cardarelli, F.; Pozzi, D.; Caracciolo, G. - 01a Articolo in rivista
paper: PHARMACEUTICS (Basel: MDPI, 2009-) pp. - - issn: 1999-4923 - wos: WOS:000519268500083 (16) - scopus: 2-s2.0-85079032252 (16)

11573/1706151 - 2020 - Protein corona-enabled serological tests for early stage cancer detection
Quagliarini, E.; Di Santo, R.; Pozzi, D.; Caracciolo, G. - 01a Articolo in rivista
paper: SENSORS INTERNATIONAL (Beijing: Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.) pp. - - issn: 2666-3511 - wos: (0) - scopus: 2-s2.0-85098606391 (14)

11573/1466693 - 2020 - Mechanistic insights into the release of doxorubicin from graphene oxide in cancer cells
Quagliarini, E.; Di Santo, R.; Pozzi, D.; Tentori, P.; Cardarelli, F.; Caracciolo, G. - 01a Articolo in rivista
paper: NANOMATERIALS (Basel : MDPI) pp. - - issn: 2079-4991 - wos: WOS:000567663200001 (17) - scopus: 2-s2.0-85090649973 (21)

11573/1416233 - 2019 - Microfluidic-generated lipid-graphene oxide nanoparticles for gene delivery
Di Santo, R.; Quagliarini, E.; Palchetti, S.; Pozzi, D.; Palmieri, V.; Perini, G.; Papi, M.; Capriotti, A. L.; Lagana, A.; Caracciolo, G. - 01a Articolo in rivista
paper: APPLIED PHYSICS LETTERS (New York: American Institute of Physics) pp. 233701- - issn: 0003-6951 - wos: WOS:000471696100043 (14) - scopus: 2-s2.0-85067237550 (22)

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