Transcription activator, hyaluronic acid and tocopheryl succinate multi-functionalized novel lipid carriers encapsulating etoposide for lymphoma therapy

Delivery of chemotherapeutic drugs using nanocarriers is emerging as a promising approach for the treatment of cancer. The aim of this research was to develop a dual targeted d-α-tocopheryl succinate (TOS) functionalized nanostructured lipid carriers (NLCs), using etoposide (ETP) as a model drug to prove their in vitro and in vivo anti-tumor effects. Novel ETP loaded NLCs were constructed (ETP-NLCs). Hyaluronic acid (HA) and cell-penetrating peptide transcription activator (TAT) was applied for the surface decoration of ETP NLCs (HATOS/TATTOS-ETP-NLCs). The antitumor efficiency of HATOS/TATTOS-ETP-NLCs was evaluated in tumor bearing animal models. HATOS/TATTOS-ETP-NLCs displayed significantly higher transfection efficiency and better antitumor ability than undecorated ETP-NLCs in lymphoma cells bearing mice model. The newly constructed NLCs could successfully load drug and gene; and TAT could function as excellent targeting ligands to improve the cell targeting ability of the gene loaded nanocarriers. The resulting dual ligands decorated vectors could be a promising targeted gene delivery system for the lymphoma treatment.