"Development of enzyme-activated nano-conjugates for targeted hepatic cancer therapy" - Liver cancer is the fifth most common cancer in the world accounting for approximately one million new cases per year. Surgical resection of tumor tissue is considered a good treatment option, however, only 15% - 30% of hepatic cancer patients are operative candidates and they typically exhibit a 30%-60% recurrence rate. Other treatment options include thermal and chemical ablation, chemoembolization, and regional and systemic chemotherapy. Unfortunately, these treatment strategies are highly invasive with limited specificity towards cancer cells and have failed to improve the survival of hepatic cancer patients, which remains less than 12 months. These statistics clearly indicate the urgent clinical need for innovative drug delivery systems that can shuttle a large dose of chemotherapeutic agents selectively into the cytoplasm of hepatic cancer cells to induce the desired cancer cell death without causing nonspecific toxicity to healthy organs. To address this unmet clinical need, we have designed and synthesized a new family of targeted, water-soluble, nano-conjugates that are efficiently internalized by hepatic cancer cells and selectively release their therapeutic cargo in response to the reductive effect of intracellular enzymes in a tunable fashion. In this seminar, I will discuss the rationale behind the development of these enzyme-activated nano-conjugates, strategies to achieve 'tunable' hepatocyte-specific release of the loaded anticancer drugs, our sugar-mediated targeting approach, and the associated anticancer activity and toxicity compared to conventional approaches.