Bovine serum albumin nanoparticles modified with multilayers and aptamers for pH-responsive and targeted anti-cancer drug delivery

Abstract

The widely used bovine serum albumin (BSA) nanoparticles (NPs) were modified with poly(allylamine hydrochloride) (PAH)/sodium poly(4-styrene sulfonate) (PSS) multilayers and aptamers to improve their suspension stability and targeting ability. For this to occur, a PAH-g-poly(ethylene glycol) (PAH-g-PEG–COOH) layer was further adsorbed onto the (PAH/PSS)2 multilayer-coated BSA NPs and used to covalently bond the aptamer AS1411, which is known to specifically bind the over-expressed nucleolin on cancer cell membranes. The PEGylated multilayer-coated BSA NPs showed good suspension stability in diverse media, in particular in a serum containing medium. By a mechanism of spontaneous deposition, doxorubicin (DOX) was effectively loaded into the pre-formed BSA NPs with both good encapsulation efficiency (98.6%) and loading percentage (9%). The loaded drug showed a pH-dependent release behaviour, i.e. faster at pH 5.5 than at pH 7.4. The multilayer coating did not significantly influence either both drug loading or release. In vitro cell culture demonstrated that the as-prepared BSA NPs could be specifically delivered to liver cancer cells, leading to higher cellular uptake and cytotoxicity.