Breast cancer stem cells (BCSCs) are pan-resistant to different anticancer agents and responsible for cancer relapse. Disulfiram (DS), an antialcoholism drug, targets CSCs and reverses pan-chemoresistance. The anticancer application of DS is limited by its very short half-life in the bloodstream. This prompted us to develop a liposome-encapsulated DS (Lipo-DS) and examine its anticancer effect and mechanisms in vitro and in vivo.The relationship between hypoxia and CSCs was examined by in vitro comparison of BC cells cultured in spheroid and hypoxic conditions. To determine the importance of NFκB activation in bridging hypoxia and CSC-related pan-resistance, the CSC characters and drug sensitivity in BC cell lines were observed in NFκB p65 transfected cell lines. The effect of Lipo-DS on the NFκB pathway, CSCs and chemosensitivity was investigated in vitro and in vivo.The spheroid cultured BC cells manifested CSC characteristics and pan-resistance to anticancer drugs. This was related to the hypoxic condition in the spheres. Hypoxia induced activation of NFκB and chemoresistance. Transfection of BC cells with NFκB p65 also induced CSC characters and pan-resistance. Lipo-DS blocked NFκB activation and specifically targeted CSCs in vitro. Lipo-DS also targeted the CSC population in vivo and showed very strong anticancer efficacy. Mice tolerated the treatment very well and no significant in vivo nonspecific toxicity was observed.Hypoxia induced NFκB activation is responsible for stemness and chemoresistance in BCSCs. Lipo-DS targets NFκB pathway and CSCs. Further study may translate DS into cancer therapeutics.

Albumin nanoparticles (NP) were proved to be effective and safe carriers for delivering anticytomegaloviral compounds in the vitreous. NP improved the antiviral activity of both ganciclovir and the phosphodiester oligonucleotide analog to formivirsen. NP appeared to be fusogenic carriers able to target the nucleus of cells. In addition, these drug carriers were well tolerated when administered by the intravitreal route and did not induce autoimmune reactions.

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Legumin (storage protein from Pisum sativum L.) nanoparticles of about 250 nm were prepared by means of a pH-coacervation method and chemical cross-linking with glutaraldehyde. This preparative method enabled to avoid the use of organic solvents but only yielded about 27% of protein added as nanoparticles. No significant differences in size, percentage yieM, and surface charge were obtained between legumin nanoparticles cross-linked with different glutaraldehyde concentrations. Legumin nanoparticles were quite stable in phosphate-buffered saline (PBS). They follow a zero-order degradation, and by increasing gluraraldehyde concentration, a longer half-life (t5,,) was obtained. The amount of methylene blue (MB), used as a model of hydrophilic drug, loaded was about 6.2% of the initial dye. Its release from the nanoparticles consisted of a rapid initial phase followed by a slower second period. The rates in this second phase were inversely related to the degree of cross-linking. 841

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