Innovative approaches for cancer treatment: current perspectives and new challenges Carlotta Pucci1a, Chiara Martinelli1b and Gianni Ciofani1,2c

Cancer accounts for millions of deaths every year and, due to the increase and aging of the world population, the number of new diagnosed cases is continuously rising. Although many progresses in early diagnosis and innovative therapeutic protocols have been already set in clinical practice, still a lot of critical aspects need to be addressed in order to efficiently treat cancer and to reduce several drawbacks caused by conventional therapies. Nanomedicine has emerged as a very promising approach to support both early diagnosis and effective therapy of tumors, and a plethora of different inorganic and organic multifunctional nanomaterials have been ad hoc designed to meet the constant demand for new solutions in cancer treatment. Given their unique features and extreme versatility, nanocarriers represent an innovative and easily adaptable tool both for imaging and targeted therapy purposes, in order to improve the specific delivery of drugs administered to cancer patients. The current review reports an in-depth analysis of the most recent research studies aiming at developing both inorganic and organic materials for nanomedical applications in cancer diagnosis and therapy. A detailed overview of different approaches currently undergoing clinical trials or already approved in clinical practice is provided.

Accumulation of reactive oxygen species in cells leads to oxidative stress, with consequent damage for cellular components and activation of cell-death mechanisms. Oxidative stress is often associated with age-related conditions, as well as with several neurodegenerative diseases. For this reason, antioxidant molecules have attracted a lot of attention, especially those derived from natural sources─like polyphenols and tannins. The main issue related to the use of antioxidants is their inherent tendency to be oxidized, their quick enzymatic degradation in biological fluids, and their poor bioavailability. Nanomedicine, in this sense, has helped in finding new solutions to deliver and protect antioxidants; however, the concentration of the encapsulated molecule in conventional nanosystems could be very low and, therefore, less effective. We propose to exploit the properties of tannic acid, a known plant-derived antioxidant, to chelate iron ions, forming hydrophobic complexes that can be coated with a biocompatible and biodegradable phospholipid to improve stability in biological media. By combining nanoprecipitation and hot sonication procedures, we obtained three-dimensional networks composed of tannic acid–iron with a hydrodynamic diameter of ≈200 nm. These nanostructures show antioxidant properties and scavenging activity in cells after induction of an acute chemical pro-oxidant insult; moreover, they also demonstrated to counteract damage induced by oxidative stress both in vitro and on an in vivo model organism (planarians).

We describe the rapid isolation of single-domain recombinant antibodies in VHH format from a pre-immune llama library created in our laboratory. Such naïve library has demonstrated to be a versatile tool and enabled the isolation of several different antibodies for any of the six proteins panned in parallel. The binders specific for human fibroblast growth factor receptor 1 (FGFR1) were successively analyzed in more detail and resulted suitable for both western blot and immunofluorescence analyses. Several milligrams per liter of antibodies were purified by affinity chromatography and used for kinetic and thermodynamic characterization. Their K_D was in the nanomolar range and they apparently bound a FGF receptor 1 domain not overlapping the region recognized by its physiological ligand FGF. Altogether, the collected data indicate that the new library can enable the recovery of binders of high affinity, specificity and functionality in the conventional immunological tests, avoiding the necessity of further maturation steps. Such results confirmed recent reports of high affinity pre-immune IgNARs and supported the choice of using large single-domain recombinant antibody naïve libraries as an alternative to the preparation of immune libraries for selecting monoclonal antibodies, at convenient cost and time conditions.