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Bexarotene (BEX), a high-affinity agonist for retinoid X receptors (RXRs), shows apparent biological activities and distinct inhibitive efficacy in both cancer therapy and prevention. This study exploited a folatedecorated delivery of bexarotene-loaded bovine serum albumin nanoparticles, which could solubilize the poorly water-soluble drug and overcome the nonspecific targeting disadvantage. Bexarotene-loaded bovine serum albumin nanoparticles (BEX-BSANPs) were optimized by a desolvation technique, subsequently conjugated with folate by carbodiimide reaction. The resultant folate-modified bexarotene-loaded bovine serum albumin nanoparticles (FA-BEX-BSANPs) showed a spherical shape, with a diameter of 195.3 AE 5.6 nm, a zeta potential of À33.64 AE 1.97 mV, and 71.28 AE 1.93 mg folate was coupled per mg BSA. Differential scanning calorimetry and X-ray diffraction analysis confirmed the amorphous state of bexarotene in the folate-conjugates. The in vitro drug release of bexarotene presented a controlled and sustained release pattern. The in vitro cytotoxicity, cell apoptosis and cellular uptake experiments of the nanoparticles were performed by MTT assay, propidium iodide staining, fluorescence microscopy and flow cytometric analysis on A549 and MCF-7 cancer cells. Both the BEX-BSANPs and FA-BEX-BSANPs induced an enhanced cancer cell apoptotic effect in contrast to BEX solution. The cells showed an excellent binding for folate-modified nanoparticles. Especially, the interference effect on the cellular internalization process by an excess folic acid was relatively dramatic for the FR-positive MCF-7 cells in comparison to the modest change seen in the FR-negative A549 cell lines, indicating that the uptake was mediated by the folate receptors. Together these data suggested that the folate-modified bexarotene-loaded delivery system, which demonstrated better biocompatibility and potential superiority, could be an appropriate cancer therapy in targeting tumors in the future. † Electronic supplementary information (ESI) available: The cell culture, MTT assay, propidium iodide staining process, cellular uptake, ow cytometric analysis, inuence of the molar ratio of FA to BSA and reaction time on the folate content conjugating to BSA, cell viabilities of blank nanoparticles, uorescence microscopy images, preparation of BEX-BSANPs, conjugate conditions and results of FA-BSANPs and the value of uorescence intensity. See

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