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Site-specific drug delivery is an effective approach to decreasing drug toxicity and enhancing therapeutic effects. In this study, zein was decorated with folic acid (FA) for targeted delivery of 10-hydroxycamptothecin (HCPT). The reaction process was monitored using an online ATR-UV spectrophotometer, and the conjugation degree was quantified using a UV–vis spectrophotometer. Successful conjugation was evidenced using FT-IR and 1H NMR. The influence of FA conjugation on the self-assembly of zein molecules and cellular uptake was investigated in detail. FA conjugation facilitates the formation of small nanoparticles with good dispersity and stability and improves the cellular uptake in folate receptor positive cells. HCPT nanocrystals (NC) were prepared and incorporated into FA-zein. The drug release behavior of HCPT NC/FA-zein nanoparticles is more consistent with a diffusion mechanism than a matrix swelling/erosion mechanism of HCPT NC/zein particles; and HCPT NC/FA-zein nanoparticles induce higher antitumor activity in folate receptor positive cells at low HCPT-equivalent concentration. These results suggest that FA-zein is a potential carrier material for sustained and targeted delivery of anticancer drugs.

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