Hepatitis B virus (HBV) chronically infects more than 250 million individuals worldwide and is responsible for more than 800,000 deaths per year by promoting end-stage liver diseases, among which decompensated cirrhosis and hepatocellular carcinoma (HCC) (WHO, July 2020) are prominent. Studies performed in chimpanzees or in animalversion of HBV (woodchuck HBV: WHBV) highlighted the lack of immune responses against the virus upon primary infection.

Antibiotics can treat the acute phase of a disease, but often do not completely clear the etiologic agent, allowing the pathogen to establish persistent infection that can revive the disease in a frustrating recurrence of infection. The mechanisms that control chronic bacterial infections are complex and involve pathogen adaptations that favor survival from both host immune responses and antibiotic bactericidal activity.

Since the discovery of the hepatitis B virus (HBV) by Blumberg et al., great progress has been made in understanding the pathogenesis of the virus and its role in hepatocellular carcinoma (HCC). It is estimated that hepatitis B is responsible for about 50% of the HCC cases worldwide. Because of geographic variations in HBV incidence, the burden of HBV-related HCC (HBV-HCC) is highest in endemic areas such as Asian-Pacific and sub- Saharan Africa and lowest in the United States and the West.

Tenofovir, alias (R)-PMPA, was first divulged as an anti- HIV agent in 1993 [1]. That it would in 2012, become the first antiretroviral agent, approved by the US FDA (Food and Drug Administration) to prevent HIV infection, could have been predicted from the findings of Tsai et al.

Encapsulation of therapeutic molecules (e.g., small molecule inhibitors, mRNA, siRNA, aptamers, etc.) into nanomaterials can improve the solubility and blood circulation of the drugs, alter their biodistribution, decrease their toxicities, overcome drug resistance, and facilitate their entry into target cells. The development of anti-cancer nanodrugs has been the focus of intense study for decades. Several anti-cancer nanodrugs have been approved for clinical use all over the world.