Abstract
In this work, we developed a novel technique to prepare pH-responsive charge reversal nanospheres based on softwood kraft lignin (SKL) through two steps modification and high efficient self-assembly. SKL was first grafted with imidazole groups by Mannich reaction and further fabricated into acetylated histidine-modified lignin (Ace-SKL-HIS) via acetylation reaction. Ace-SKL-HIS nanospheres (Ace-SKL-HIS NPs) were prepared by fast vacuum evaporation method, their effective diameters (ED) were around 100 nm, exhibited low Polydispersity Index(PDI, <0.2) and good shape. Ace-SKL-HIS NPs demostrated excellent pH response performance with charge reversal under acidic environment. Then, curcumin was applied as a model drug to prepare drug-loaded nanospheres (Ace-SKL-HIS@CUR). The drug loading degree (DL%) and encapsulation efficiency (EE%) were 22.34 % and 70.76 %, respectively. The in vitro release behavior of curcumin exhibited excellent pH dependent release property, 76.82 % release at pH 5.7 while only 12.92 % at pH 7.4 in 120 h. Furthermore, in vitro cytotoxicity studies showed that Ace-SKL-HIS@CUR had potent anti-tumor effect, with IC50 of 28.16 μg/ mL. This study constructed a promising nanocarrier platform for cancer drug delivery, which paved a new way to the high value-added application of lignin.
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