Dual-modified albumin-polymer nanocomplexes with enhanced in vivo stability for hepatocellular carcinoma therapy

Etoposide (ETO) is a semi-synthetic derivative of podophyllotoxin with a definite antitumour effect, but its use is hampered by poor solubility and numerous side-effects. In this work, we developed a hyaluronic acid and ethylenediamine dual-modified albumin-polymer nanocomplex for tumour targeted delivery of ETO. The ETO loaded dual-modified albumin-polymer nanocomplexes (E-HEAP NCs) was composed of a hyaluronic acid decorated cationic albumin shell and a stable poly (butyl cyanoacrylate) core. E-HEAP NCs exhibited a high encapsulation efficiency, great stability in vivo. Furthermore, blank HEAP NCs carrier showed excellent biocompatibility in vitro cell cytotoxicity assay. While, E-HEAP NCs represented superior inhibitory effect on HepG2 cells than free ETO. Additionally, E-HEAP NCs exhibited an excellent tumour-targeting effect, due to the enhanced targeting efficacy of hyaluronic acid and albumin-mediated transcytosis. Moreover, E-HEAP NCs displayed an enhanced antitumour effect and extended the survival period in tumour bearing mice. In summary, the developed novel protein-polymer nanocomplex can potentially serve as a drug delivery system for improved cancer therapy.