"1. Polymer nanoparticles with a core-shell structure have been designed and characterized.
I used 3 different polyurethanes to compose the particle core and a mixture of phospholipids to obtain a biocompatible shell.
I demonstrated that these particles can be used to co-encaspulate multiple drugs and imaging agents with high entrapment efficiency and are able to co-deliver them to tumors to a significantly higher extent as compared to free drugs.
This work has been published in Acta Biomaterialia (2018).
the same particle design was exploited in the return phase to encapsulate and release in a controlled fashion microRNA molecules for cell reprogramming
2. Once demonstrated the validity of this nanoparticle approach, I designed and characterized an intracranial drug delivery system for the delivery of a potent proteasome inhibitor. This drug has shown high cytotoxicity in vitro on different GBM cell lines, including GBM stem cells (GSCs).
3. Intracranial retention and distribution of fluorescent nanoparticles loaded with a fluorescent drug surrogate was studied in vivo on tumor-free and tumor-bearing mice. We demonstrated that intracranial injection of nanoparticles or nanoparticles embedded in a commercial polymer hydrogel is feasible and safe for animals. We showed that the hydrogel enhances intra-tumor retention of nanoparticles and drug, by using in vivo imaging system. We also analyzed drug distribution in the brain after 24h, 5days, 10 days and 20 days post-injection, by fluorescence analysis and quantification on at least 20 coronal sections of the brains (4 mice/group). We showed that nanoparticles remain in the tumor, are internalized by cancer cells in vivo, and migrate through the corpus callous, main route of GBM cells invasion.
4. I demonstrated that intra-cranial treatment with nanoparticles significantly extends the survival of GBM bearing mice (injected with a GSCs-derived tumor or U87 tumors). Some preliminary investigations on the reasons for tumor recurrence after intra-cranial treatment have also been performed, to identify possible combination therapies that may further extend survival. Periostin secretion, enhanced vascularization, and enhanced TWIST expression was detected after treatment with drug-loaded nanoparticles. Strategies addressed at the concomitant inhibition of these factors may further improve treatment of these tumors.
The use of the HG only partially extended the survival of mice with respect to free nanoparticles, but not in a significant fashion.
Results have been disseminated at international and national events:
a. IV workshop ""RESEARCH AND NANOMEDICINE"" organized in Pavia (Italy) for Ph.D. students (18/06/2019) - Oral Presentation for master and Ph.D. students (50 participants)
b. Keystone Symposium ""Cancer Metastasis: The Role of Metabolism, Immunity and the Microenvironment"" Florence, March 15 - March 19, 2019 - Poster Presentation (approx. 500 participants)
c.30th EUROPEAN SOCIETY FOR BIOMATERIALS CONFERENCE, 09-13 September 2019 Dresden (Germany) - Poster Presentation and Flash Oral Presentation (approx. 900 participants)
d.Invited lecture for students of the Master Course in Bioengineering and Mechanical Engineering (course of Materials Process and Manufacturing )(University of Newcastle, UK) Feb. 28 2019 Oral Presentation for master students (100 participants) and short lecture for post doctoral fellows (10 participants)
e. Three peer-reviewed publications have been published in high-impact journals. One publication is currently under review in Acta Biomaterialia."
