GRAPHY

Materials confined to the nanoscale have received a boom for application in cancer therapy due to their ability to passively accumulate in the malignant site. In this way, nanomaterials hold a great potential for enhancing the efficacy and safety of anticancer treatments. Among the different types of nanomaterials, reduced graphene oxide (rGO) has a tremendous potential for anticancer applications due to its near infrared absorption and drug loading capacity. We demonstrated that, upon interaction with near infrared light, rGO produces a temperature increase that can per se induce cancer cells’ death and may trigger the release of the encapsulated drugs. Due to the near infrared light properties, the photothermal heating mediated by rGO is confined to the tumor, eliciting minimal side effects. In the last 5 years, our team uncovered novel rGO synthesis/functionalization routes with the intent to push its translation. Recently, our team optimized a novel environmentally friendly protocol to synthesize rGO by using dopamine (termed as DOPA-rGO henceforward). The DOPA-rGO has potential to be a next-generation nanomaterial for cancer therapy due to its: i) excellent biocompatibility, ii) great photothermal capacity, iii) catechol-based surface chemistry, and iv) native colloidal stability. Our team also unveiled that the nanomaterials’ photothermal heating can induce the release of Tumor-associated antigens from cancer cells. This game-changer event can unlock immune responses towards distant cancer cells (metastases). Moreover, DOPA-rGO can also be loaded with Immunostimulants that can potentially escalate this photothermally-enhanced immune response.  Despite rGO potential, its clinical translation has not yet been achieved. Since 2010 only 3 anti-cancer nanomedicines were approved by EMA. Systemically administered nanostructures rely on the Enhanced Permeability and Retention effect to achieve tumor uptake. However, the pre-clinical cancer models present an overexaggerated Enhanced Permeability and Retention effect, which is not ubiquitously present on human solid tumors. In fact, only 0.7% of the intravenously injected nanomaterial dose reaches the tumor, which explains nanomedicines’ poor translation. In order to apply DOPA-rGO incorporating Immunostimulants in cancer immuno-photothermal therapy, it is crucial to surpass the nanomaterials’ systemic administration problems. Our team noticed that thiol-ene click injectable in situ forming hydrogels are a novel technology that can be used to perform the local delivery of DOPA-rGO/Immunostimulants directly into the tumor site.  This project aims to engineer a novel class of thiol-ene click injectable in situ forming hydrogels incorporating DOPA-rGO/Immunostimulants, and perform the in vitro validation of their potential for cancer immuno-photothermal therapy. This project will comprise 4 tasks performed in close collaboration by the CICS, ITQB, and UNICAM teams, which have established experience in these subjects. Overall, the envisioned thiol-ene click injectable in situ forming hydrogels are a scalable, environmentally friendly and beyond state-of-the-art technology that may unravel a new i) local administration approach for nanomaterials and ii) strategy for metastatic breast cancer treatment. By addressing these critical state-of-the-art problems, this project will impact the scientific community, industry, society and economy.