Antonella Grigoletto
 | Department of Pharmaceutical and Pharmacological Sciences, University of Padova |
Short CV
Antonella Grigoletto received a master degree in Pharmaceutical Chemistry and Technology in 2011 at the University of Padova and obtained her PhD in Pharmaceutical Sciences at the Doctoral School of Molecular Sciences at the University of Padova in 2015 (Supervisor: Prof. G. Pasut). In 2014 she moved, as exchange PhD student, to the Drexel University College of Medicine in Philadelphia (USA) at the Department of Biochemistry and Molecular Biology in the research lab of Prof. Irwin Chaiken. From 2015 to 2021 she was a Post Doc researcher at the University of Padova where she gained a multidisciplinary technical and scientific experience, team supervision and coordination of 9 master students. Since 2022 she is a Researcher and Assistant Professor of Pharmaceutical Technology (SSD CHIM09). Since 2022 she is a Researcher and Assistant Professor of Pharmaceutical Technology and Galenic Formulation (SSD CHIM/09) at the Department of Pharmaceutical and Pharmacological Sciences, University of Padova.
Teaching
Office hours
Please, fix an appointment by email.
Availability for Thesis Projects
The ongoing research projects are:
- Formulation of stealth cationic liposomes for gene theraphy.
Due to its intrinsic characteristics, the negatively charged genetic material cannot cross cell membranes. Furthermore, it is rapidly degraded by nucleases or in lysosomes. Cationic liposomes provide an effective delivery system for transporting and protecting plasmid DNA or RNA to the site of action. - Actin-resistant acidic DNase for the treatment of Cystic Fibrosis pulmonary symptoms.
Recombinant human deoxyribonuclease (rhDNase) is the most widely used mucolytic agent in the treatment of CF, but it has several limitations. We are investigating a new human DNase isoform, DNase1L2, with promising therapeutic potential for CF. - Conjugation of hyaluronic acid to proteins for the development of protein-based vaccines.
We are exploiting hyaluronic acid as a natural and effective immunological adjuvant for protein-based vaccines. - Development of a Drug Delivery Module (DDM) composed of PEG-CROMOC-drug.
This platform facilitates the efficient cellular uptake of cargo, enabling the transport of small drugs as well as biomolecules with high molecular mass. CROMOC is profiled in several forms of cancer, including liver and lung cancer.
The projects are only briefly introduced. For more information please come to visit the lab and meet in person after fixing an appointment by email.
Students will learn to use several instruments: HPLC and FPLC, NanoAssemblr® (liposome formulation), UV-Vis spectrophotometer (colorimetric assays, activity assays), Circular Dichroism, DLS (size and zeta-potential measurements), NMR (polymers modification), ESI-TOF, MALDI-TOF, freeze dryer. Students will apply different chromatographic (Reverse Phase, Size Exclusion and Ion Exchange Chromatography, TLC) and electrophoretic techniques (SDS-PAGE and Agarose gel electrophoresis).
Research
Scientific Activities
My research interest is focused on protein, drug and gene delivery. The delivery of therapeutic agents to the appropriate site of action, a concept summed up in the “magic bullet” model proposed by Ehrlich over 100 years ago, is one of the critical points of pharmaceutical research. An efficient and targeted delivery of the bioactive molecules can really change the outcomes of the therapies in terms of increased exposure of the active drugs, reduction of the side effects, improvement of patient compliance. Over the years, a deeper understanding of physiopathological conditions of disease has amplified the possibility of designing tailored drug delivery platforms that carry drugs, several copies of the same drug, or different drugs in combination, preferentially to the appropriate site of action. The design rationale to develop a successful delivery system will provide new and improved means to treat many intractable diseases and disorders. Polymer conjugation of protein and drugs, and delivery platforms like liposomes for the delivery of genetic materials are my specific research topics.
Technical expertise
Extensive experience in:
- polymer conjugation, using chemical and enzymatic methods, of therapeutic proteins and drugs;
- liposomes formulation by microfluidics or by thin layer evaporation (TLE) and extrusion;
- active targeting of liposomes with proteins and peptides;
- polymer modification and characterization;
- protein modification with drugs and dyes;
- protein characterization;
- pharmacokinteic and pharmacodynamic studies on mice and rats
Others competences:
- Protein expression in microbial cultures and purification (IMAC, IEX, SEC);
- Microwave-assisted solid-phase peptide synthesis.
Analytical techniques:
- RP-, SEC-, HIC, IEX-HPLC,
- UPLC,
- FPLC,
- TLC,
- UV-Vis, Fluorescence and Circular Dichroism spectroscopy,
- Dynamic Light Scattering (DLS),
- 1H-NMR and DOSY 1H-NMR spectroscopy,
- Mass spectrometry (ESI-TOF, MALDI-TOF),
- SDS-PAGE, Western Blot, Agarose gel electrophoresis,
- ELISA,
- Peptide mass fingerprint,
- Analytical Rheology,
- Surface Plasmon Resonance (SPR)
Publications Grigoletto
MAIN PUBLICATIONS
- Tedeschini T, Campara B, Grigoletto A, Bellini M, Salvalaio M, Matsuno Y, Suzuki A, Yoshioka H, Pasut G. Polyethylene glycol-based linkers as hydrophilicity reservoir for antibody-drug conjugates. J Control Release. 2021 Sep 10;337:431-447. doi: 10.1016/j.jconrel.2021.07.041.
- Grigoletto A, Martinez G, Gabbia D, Tedeschini T, Scaffidi M, Martin S, Pasut G. Folic Acid-Targeted Paclitaxel-Polymer Conjugates Exert Selective Cytotoxicity and Modulate Invasiveness of Colon Cancer Cells. Pharmaceutics. 2021 Jun 23;13(7):929. doi: 10.3390/pharmaceutics13070929.
- Dalla Pietà A, Carpanese D, Grigoletto A, Tosi A, Dalla Santa S, Pedersen GK, Christensen D, Meléndez-Alafort L, Barbieri V, De Benedictis P, Pasut G, Montagner IM, Rosato A. Hyaluronan is a natural and effective immunological adjuvant for protein-based vaccines. Cell Mol Immunol. 2021 May;18(5):1197-1210. doi: 10.1038/s41423-021-00667-y.
- Delfino D, Mori G, Rivetti C, Grigoletto A, Bizzotto G, Cavozzi C, Malatesta M, Cavazzini D, Pasut G, Percudani R. Actin-Resistant DNase1L2 as a Potential Therapeutics for CF Lung Disease. Biomolecules. 2021 Mar 10;11(3):410. doi: 10.3390/biom11030410.
- Grigoletto, A., Tedeschini, T., Canato, E., Pasut, G. The evolution of polymer conjugation and drug targeting for the delivery of proteins and bioactive molecules. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2020 Dec 14:e1689. doi: 10.1002/wnan.1689.
- Maso K, Grigoletto A, Raccagni L, Bellini M, Marigo I, Ingangi V, Suzuki A, Hirai M, Kamiya M, Yoshioka H, Pasut G. Poly(L-glutamic acid)-co-poly(ethylene glycol) block copolymers for protein conjugation. J Control Release. 2020 Aug 10;324:228-237. doi: 10.1016/j.jconrel.2020.05.015.
- Grigoletto, A., Maso K., Pasut, G. Enzymatic approaches to new protein conjugates. Polymer-Protein Conjugates 2020; 271-295. doi.org/10.1016/B978-0-444-64081-9.00013-9.
- Aneja R, Grigoletto A, Nangarlia A, Rashad AA, Wrenn S, Jacobson JM, Pasut G, Chaiken I. Pharmacokinetic stability of macrocyclic peptide triazole HIV-1 inactivators alone and in liposomes. J Pept Sci. 2019;25(4):e3155. doi: 10.1002/psc.3155.
- Maso K, Grigoletto A, Vicent MJ, Pasut G. Molecular platforms for targeted drug delivery. Int Rev Cell Mol Biol. 2019;346:1-50. doi: 10.1016/bs.ircmb.2019.03.001.
- Grigoletto A, Mero A, Yoshioka H, Schiavon O, Pasut G. Covalent immobilisation of transglutaminase: stability and applications in protein PEGylation. J Drug Target. 2017; 13:1-9.
- Mero A, Grigoletto A, Martinez G, Pasut G. (2016). Recent Developments in Hyaluronic Acid-Based Nanomedicine. In: Qun Zhou. Recent Advances in Biotechnology. vol. 3, p. 102-128, Bentham Science, ISBN: 978-1-68108-392-6, doi: 10.2174/97816810839261160301.
- Grigoletto A, Mero A, Zanusso I, Schiavon O, Pasut G. Chemical and Enzymatic Site Specific PEGylation of hGH: The Stability and in vivo Activity of PEG-N-Terminal-hGH and PEG-Gln141-hGH Conjugates. Macromol Biosci. 2016 Jan;16(1):50-6. doi: 10.1002/mabi.201500282.
