Sorafenib encapsulated in nanocarrier functionalized with glypican-3 specific peptide for targeted therapy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world with increasing incidence. Chemotherapy is required for HCC patients after receiving surgical resection. Serious off-target induced side effects and systemic toxicity limit the clinical utility of drugs. Targeting therapeutic nanomedicine is an innovative strategy for enhancing drug delivery efficiency and reducing side effects. Here, we successfully formulated nanocarriers to encapsulate sorafenib, an FDA approved drug for treatment of HCC. Sorafenib is encapsulated with an entrapment efficiency >80% over 20 days. The effective aqueous solubility is improved over 1900-fold. The release ratio in vitro is characterized by a half-life of T1/2 = 22.7 h. The peak target-to-background ratio for nanocarrier uptake by tumor occurs at 24 h post-injection, and is significantly greater for the target peptide versus controls. Ex vivo biodistribution confirms the in vivo results. Tumor regression is significantly greater for the target peptide versus controls after 21 days of therapy. No acute toxicity is found by blood chemistry or necropsy. In summary, a peptide specific for GPC3 has been identified, and used to modify the surface of a nanocarrier that encapsulates sorafenib with high entrapment efficiency. Regression of HCC xenograft tumors showed promise for targeted drug delivery.