Despite numerous studies on the contamination of organophosphate triesters (tri-OPEs) in indoor environments, organophosphate diesters (di-OPEs) have rarely been investigated. The present study aimed to investigate whether di-OPEs coexist with tri-OPEs in house dust collected from Guangzhou (n = 30), South China and the city of Carbondale (n = 17) located in the Midwestern United States (U.S.). Median concentrations of bis­(2-butoxyethyl) phosphate (BBOEP), bis­(1-chloro-2-propyl) phosphate (BCIPP), bis­(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis­(2-ethylhexyl) phosphate (BEHP), bis­(2-methylphenyl phosphate) (BMPP), and diphenyl phosphate (DPHP) were determined to be 15.9, < LOQ, 33.6, 654, 9.5, and 605 ng/g in South China house dust, and 1580, 90.6, 234, 867, 4.0, and 6500 ng/g in Midwestern U.S. dust, respectively. The total concentrations of di-OPEs (referred to ΣdiOPEs) constituted an average of 22.9% and 21.3% of the total concentrations of tri-OPEs in dust from these two locations, respectively. Median concentration ratios of DPHP and BEHP to their respective tri-OPEs (i.e., TPHP and TEHP) were determined to be 1.1 and 1.0 in South China dust and 3.7 and 1.4 in Midwestern U.S. dust, respectively, indicating possible commercial applications for these two di-OPEs. Correlative analyses reveal chemical- and region-specific relationships between di-OPEs and their respective tri-OPEs, suggesting that the relative importance of different sources (e.g., direct commercial use, impurity in tri-OPE formulas, and tri-OPE degradation) could vary for different di-OPEs. Our findings demonstrate wide occurrences of di-OPEs in an indoor environment from the studied locations and raise concerns on human exposure to dust associated di-OPEs. Future studies are needed to explore more possible di-OPEs in indoor environments and elucidate their sources, human exposure pathways, and toxicokinetics.

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This study investigated the therapeutic efficiency of monomethoxy polyethylene glycol-poly(lactic-co-glycolic acid) (mPEG-PLGA) co-loaded with syringopicroside and hydroxytyrosol as a drug with effective targeting and loading capacity as well as persistent circulation in vivo. The nanoparticles were prepared using a nanoprecipitation method with mPEG-PLGA as nano-carrier co-loaded with syringopicroside and hydroxytyrosol (SH-NPs). The parameters like in vivo pharmacokinetics, biodistribution in vivo, fluorescence in vivo endomicroscopy, and cellular uptake of SH-NPs were investigated. Results showed that the total encapsulation efficiency was 32.38 ± 2.76 %. Total drug loading was 12.01 ± 0.42 %, particle size was 91.70 ± 2.11 nm, polydispersity index was 0.22 ± 0.01, and zeta potential was -24.5 ± 1.16 mV for the optimized SH-NPs. The nanoparticle morphology was characterized using transmission electron microscopy, which indicated that the particles of SH-NPs were in uniformity within the nanosize range and of spherical core shell morphology. Drug release followed Higuchi kinetics. Compared with syringopicroside and hydroxytyrosol mixture (SH), SH-NPs produced drug concentrations that persisted for a significantly longer time in plasma following second-order kinetics. The nanoparticles moved gradually into the cell, thereby increasing the quantity. ALT, AST, and MDA levels were significantly lower on exposure to SH-NPs than in controls. SH-NPs could inhibit the proliferation of HepG2.2.15 cells and could be taken up by HepG2.2.15 cells. The results confirmed that syringopicroside and hydroxytyrosol can be loaded simultaneously into mPEG-PLGA nanoparticles. Using mPEG-PLGA as nano-carrier, sustained release, high distribution in the liver, and protective effects against hepatic injury were observed in comparison to SH.

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BACKGROUND Norcantharidin (NCTD) is suitable for the treatment of primary liver cancer, especially early and middle primary liver cancer. This compound can reduce tumors and improve immune function. However, the side effects of NCTD have limited its application. There is a marked need to reduce the side effects and increase the efficacy of NCTD. AIM To develop a nanomaterial carrier, NCTD-loaded metal-organic framework IRMOF-3 coated with a temperature-sensitive gel (NCTD-IRMOF-3-Gel), aiming to improve the anticancer activity of NCTD and reduce the drug dose. METHODS NCTD-IRMOF-3-Gel was obtained by a coordination reaction. The apparent characteristics and in vitro release of NCTD-IRMOF-3-Gel were investigated. Cell cytotoxicity assays, flow cytometry, and apoptosis experiments in mouse hepatoma (Hepa1-6) cells were used to determine the anti-liver cancer activity of NCTD-IRMOF-3-Gel in in vitro models. RESULTS The particle size of NCTD-IRMOF-3-Gel was 50-100 nm, and the particle size distribution was uniform. The release curve showed that NCTD-IRMOF-3-Gel had an obvious sustained-release effect. The cytotoxicity assays showed that the free drug NCTD and NCTD-IRMOF-3-Gel treatments markedly inhibited Hepa1-6 cell proliferation, and the inhibition rate increased with increasing drug concentration. By flow cytometry, NCTD-IRMOF-3-Gel was observed to block the Hepa1-6 cell cycle in the S and G2/M phases, and the thermosensitive gel nanoparticles may inhibit cell proliferation by inducing cell cycle arrest. Apoptosis experiments showed that NCTD-IRMOF-3-Gel induced the apoptosis of Hepa1-6 cells. CONCLUSION Our results indicated that the NCTD-IRMOF-3-Gel may be beneficial for liver cancer disease treatment.

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