Mesoporous silica-glycopolymer hybrid nanoparticles for dual targeted chemotherapy and gene therapy to liver cancer cells.

The development of nanocarriers for pharmaceutical applications is a challenging research field as they have to fulfil several requirements, such as suitable physicochemical properties, biocompatibility, loading capacity for therapeutic agents, high stability in the bloodstream, and specific delivery to the target cells. This task becomes even more difficult when trying to transport two different therapeutic agents simultaneously, as is required by most of the current therapeutic strategies. Mesoporous silica nanoparticles (MSN) fulfil most of these requirements, although they partially fail in the last two. However, these weaknesses can be circumvented if they are combined with another type of material such as polymers. In this context, the main goal of this research work was to develop MSN-based nanocarriers capable to co-transport drugs and nucleic acids and to specifically deliver them in liver cancer cells. To this end, we have prepared MSNs coated with lactobionic acid-based copolymers, as lactobionic acid has a high binding affinity to asialoglycoprotein receptors (ASGPR), which are overexpressed in liver cells. The designed hybrid MSN-based nanocarriers exhibited appropriate physicochemical properties, high ASGPR specificity and high biological activity. These MSN-glycopolymer hybrid nanosystems showed a 280-fold higher transfection activity in liver cancer cells than bare MSN particles. Furthermore, we demonstrated the ability of these nanosystems to efficiently mediate a combined antitumor strategy involving HSV-TK/GCV suicide gene therapy and chemotherapy (epirubicin), in liver cancer cells. Overall, the data obtained showed the great potential of this MSN-based nanoplatform to be applied in combined therapeutic strategies for the treatment of liver cancer.