Epigenetic inhibition assisted chemotherapeutic treatment of lung cancer based on artificial exosomes.

ABSTRACT

We adopted a novel strategy by combining histone deacetylase (HDAC) inhibitors with traditional chemotherapeutics to treat solid tumors. However, chemotherapeutics often have a narrow therapeutic index and need multiple administrations with undesired side effects that lead to the intolerance. To reduce the non-specificity of chemotherapeutics, targeted therapy was introduced to restrict such agents in the tumor with minimum effects on other tissues. We developed bioinspired artificial exosomes (AE), which enabled to deliver chemotherapeutics to the tumors effectively after systemic administration. AE were produced by incorporating membrane proteins from cancer cells into phospholipid liposomes that mimicked the plasma membrane. The synthesized AE were used for the delivery of broad-spectrum chemotherapeutic doxorubicin (DOX) and vorinostat (SAHA), an epigenetic inhibitor. The combination of DOX and SAHA showed synergistic effects on suppressing non-small cell lung cancer cells and xenograft tumors without apparent adverse effects. AE facilitated the delivery of drugs to tumor tissue and extended the retention time of drugs within tumors. Taken together, these studies suggest that the bioengineered artificial exosomes may serve as novel delivery strategy for chemotherapeutics to treat non-small cell lung cancer.