Ricerc@Sapienza

Since around 50 years ago, the academic world is developing knowledge and technology to understand and to control matter at the nanoscale in order to exploit the peculiar mechanical, electrical, optical and magnetic properties emerging when a discrete number of atoms is assembled in structures which must be described according to the weird rules of quantum mechanics.

Supramolecular architectures involving DNA bases can have a strong impact in several fields such as nanomedicine and nanodevice manufacturing. To date, in addition to the four canonical nucleobases (adenine, thymine, guanine and cytosine), four other forms of cytosine modified at the 5 position have been identified in DNA. Among these four new cytosine derivatives, 5-carboxylcytosine has been recently discovered in mammalian stem cell DNA, and proposed as the final product of the oxidative epigenetic demethylation pathway on the 5 position of cytosine.

In the last decade, many innovative nanodrugs have been developed, as well as many nanoradiocompounds that show amazing features in nuclear imaging and/or radiometabolic therapy. Their potential uses offer a wide range of possibilities. It can be possible to develop nondimensional systems of existing radiopharmaceuticals or build engineered systems that combine a nanoparticle with the radiopharmaceutical, a tracer, and a target molecule, and still develop selective nanodetection systems.

Although the term “epithelial to mesenchymal transformation” was used for the first time by Betty Hay in 1968, the earliest description of the EMT process probably dates back to drawings made by the Nobel Prize Santiago Ramòn y Cajal around 1890 (López-Novoa and Nieto, 2009).

More than 20 years after its approval by the Food and Drug Administration (FDA), liposomal doxorubicin (DOX) is still the drug of choice for the treatment of breast cancer and other conditions such as ovarian cancer and multiple myeloma. Yet, despite the efforts, liposomal DOX did not satisfy expectations at the clinical level. When liposomal drugs enter a physiological environment, their surface gets coated by a dynamic biomolecular corona (BC).

Temozolomide (TMZ) is the current first-line chemotherapy for treatment of glioblastoma multiforme (GBM). However, similar to other brain therapeutic compounds, access of TMZ to brain tumors is impaired by the blood-brain barrier (BBB) leading to poor response for GBM patients. To overcome this major hurdle, we have synthesized a set of TMZ-encapsulating nanomedicines made of four cationic liposome (CL) formulations with systematic changes in lipid composition and physical-chemical properties.

Nowadays, liposomes are the most successful drug delivery systems with a dozen drug products available in the clinic. Grafting poly-(ethylene glycol) (PEG) onto the liposome surface prevents protein binding thus prolonging blood circulation, while synthetic modification of the terminal PEG molecule with ligands (e.g. monoclonal antibodies and peptides) should promote selective accumulation in the tumor region with respect to healthy tissues. However, despite big efforts, advances have not outgrown the development stage and just a few targeted liposomal drugs are commercially available.

Today, early disease detection (EDD) is a matter of more importance than ever in medicine. Upon interaction with human plasma, nanoparticles are covered by proteins leading to formation of a biomolecular corona (BC). As the protein patterns of patients with conditions differ from those of healthy subjects, current research into technologies based on the exploitation of personalized BC patterns could be a turning point for early disease detection. Here, we present a framework based on principal component analysis of large personalized BC datasets.

Once embedded in a physiological environment, the surface of nanoparticles (NPs) gets covered with a biomolecular corona (BC) that alters their synthetic characteristics and subsequently gives them a peculiar biological identity. Despite recent studies having clarified the role of NP composition, surface chemistry and biological source (e.g., human/animal serum or plasma) in the formation of the BC, little is known about the possible impact of molecular crowding.