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In contrast with common thought, we generated highly hydrophobic anticancer prodrug self-assembled nanoparticles without the aid of surface active substances, based on the conjugation of docetaxel to d -α-tocopherol succinate. The reduction-sensitive prodrug was synthesized with a disulfide bond inserted into the linker and was compared with a control reduction-insensitive prodrug. The morphology and stability of self-assembled nanoparticles were investigated. Cytotoxicity and apoptosis assays showed that the reduction-sensitive nanoparticles had higher anticancer activity than the reduction-insensitive nanoparticles. The reduction-sensitive nanoparticles exhibited favorable in vivo antitumor activity and tolerance compared with docetaxel Tween80-containing formulation and the reduction-insensitive nanoparticles. Taken together, the unique nanomedicine demonstrated a number of advantages: (i) ease and reproducibility of preparation, (ii) high drug payload, (iii) superior stability, (iv) prolonged circulation, and (v) improved therapeutic effect. This highly reproducible molecular assembly strategy should motivate the development of new nanomedicines. [ABSTRACT FROM AUTHOR]

Three 2-phenylpyridine-Pt complexes were synthesized. All these Pt(II) complexes showed rich photophysical properties. 3 displayed high anticancer activity against human gastric cancer cell lines. [Display omitted] • Pt(II) complexes containing phenylpyridine are presented. • Crystal structures of three new Pt(II) complexes are determined. • These Pt(II) complexes display rich photophysical properties. • Some Pt(II) complexes exhibit certain selectivity toward human gastric cancer cell lines. Three luminescent Pt(II) complexes, [Pt(5-NO 2 - ppy)(H -5-NO 2 - ppy)(Cl)] (1), [Pt(2-(2′,4′-dF)- ppy)(H -2-(2′,4′-dF)- ppy)(Cl)] (2), [Pt(2-(3′,5′-dF)- ppy)(H -2-(3′,5′-dF)- ppy)(Cl)] (3) with 2-phenyl-5-nitropyridyl (5-NO 2 - ppy), 2-(2,4-difluorophenyl)pyridine (2-(2′,4′-dF)- ppy) and 2-(3,5-difluorophenyl)pyridine(2-(3′,5′-dF)- ppy) were synthesized. FT-IR spectroscopy, multinuclear NMR spectroscopy and single-crystal X-ray crystallography were used to determine their structures. The UV–vis absorption and photoluminescence (PL) spectra of 1 – 3 were measured. 1 – 3 displayed rich photophysical properties with the maximum emission wavelengths in the range of 403 to 527 nm in the photoluminescence spectra, which demonstrated 1 – 3 have the potential to become the DNA luminescent probes in living cells. The anticancer activities of these complexes were tested in vitro by MTT assay against four tumor cell lines BGC823, MGC803 (human gastric cancer cell lines), HepG2 (human hepatocellular carcinoma), A549 (human non-small-cell lung cancer cell lines), HL-7702(human normal liver cell line). Moreover, 3 displayed highest cytotoxicity against human gastric cancer cell lines with the values of IC 50 in the range of 13.036–26.594 μM. [ABSTRACT FROM AUTHOR]

Artemisinin (ART) drugs showed declining plasma concentrations after repeated oral dosing, known as time-dependent pharmacokinetics (PK). ART and dihydroartemisinin (DHA) were adopted as representatives to evaluate the roles of first-pass effects and systemic metabolism in time-dependent PK by comparison of oral versus intravenous administration and 1 dose versus 5 consecutive doses PK in rats and dogs, respectively. The hepatic extraction ratio (ER h) and the intestinal elimination changes were further investigated in rats to distinguish the roles of hepatic first-pass effect or intestinal first-pass effect. The induction capacities of ARTs to cytochrome P450 (CYP450) in rats and human cells were evaluated as well. For ART, only the oral groups showed time-dependent PK. A fairly high ER h that obtained for ART was not sensitive to multiple oral doses. An increased elimination and CYP450 expression have also been found in the intestine. For DHA, though a significant CYP450 induction was observed, neither time-dependent PK nor changes in the first-pass effects was found. In conclusion, time-dependent PK of ART was mainly caused by the increased intestinal first-pass effect rather than hepatic first-pass effect or systemic metabolism. DHA was not involved in auto-induction elimination, thus showing no time-dependent PK. [ABSTRACT FROM AUTHOR]

[Display omitted] Targeting delivery and prolonging action duration of artemisinin drugs are effective strategies for improving antimalarial treatment outcomes. Here, dihydroartemisinin (DHA) loaded poly (lactic- co -glycolic acid) (PLGA) nanoparticles (PDNs) were prepared and further cloaked with red blood cell (RBC) membranes via electrostatic interactions to yield RBC membrane-cloaked PDNs (RPDNs). The prepared RPDNs displayed a notable "core-shell" structure, with a negative surface charge of −29.2 ± 4.19 mV, a relatively uniform size distribution (86.4 ± 2.54 nm, polydispersity index of 0.179 ± 0.011), an average encapsulation efficiency (70.1 ± 0.79%), and a 24-h sustained-release behavior in vitro. Compared with PDNs, RPDNs showed markedly decreased phagocytic activity by RAW 264.7 cells and had prolonged blood circulation duration. The Pearson correlation coefficient of RPDNs distribution in infected red blood cells (iRBCs) was 0.7173, suggesting that RPDNs could effectively target Plasmodium -iRBCs. In Py By265-infected mice, RPDNs showed a higher inhibition ratio (88.39 ± 2.69%) than PDNs (83.13 ± 2.12%) or DHA (58.74 ± 3.78%), at the same dose of 8.8 μmol/kg. The ED 90 of RPDNs (8.13 ± 0.18 μmol/kg) was substantially lower than that of PDNs (14.48 ± 0.23 μmol/kg) and DHA (17.67 ± 3.38 μmol/kg). Furthermore, no apparent abnormalities were detected in routine blood examination, liver function indexes, and pathological analysis of tissue sections of Py By265-infected mice following RPDNs treatment. In conclusion, the prepared RPDNs exhibited enhanced antimalarial efficacy, prolonged circulation, targeted delivery to Plasmodium -iRBCs, and satisfactory biocompatibility. [ABSTRACT FROM AUTHOR]

• DTX-S-S-DHA conjugates were synthesized using two-step reaction and furtherly assembled to nanoparticles (DSDNs). • Reductive sensitive release of the DSDNs. • Nanoconjugates enhanced synergistic effect on tumor cells. • Nanoconjugates protected healthy tissues from drugs toxicity. Co-delivery of anti-tumor agents with outstanding stimulus-triggered drug release in tumor cells, especially with the aid of nanotechnology, provided the possibility to enhance delivery efficiency for targeting tumor cells and antitumor efficacy. In this paper, docetaxel-dihydroartemisinin nanoconjugates linked by disulfide bond were designed to increase co-delivery and anti-tumor efficacy. Docetaxel and dihydroartemisinin were synthesized using two-step reaction and furtherly assembled to nanoconjugates. Nanoprescription was optimized to evaluate its physicochemical properties. In vitro anti-tumor activities of nanoformulation were assessed by MTT. The flow cytometry was adopted to analyze cell apoptosis and cell cycle arrest. The wound healing assay was used to evaluate antimigratory-property. In vivo pharmacokinetic and pharmacodynamic studies were investigated in rats and 4T1 bearing Balb/c mice model after intravenous injection, respectively. The chemical structure of conjugate was confirmed. The prepared nanoparticles possessed uniform size distribution (172.10 ± 1.70 nm, PDI 0.05 ± 0.01), was stable during storage period, sustained release profiles and sensitive reduction responsiveness. MTT assay indicated that the toxicity of nanoconjugates was slightly weak. Flow cytometry studies showed that nanoconjugates could promote early apoptosis significantly and mainly arose from G 0 /G 1 phase. The wound healing assay provided an obvious antimetastatic potential of nanoparticles in 4T1 cells. The result of pharmacokinetic study suggested that nanoconjugates exhibited higher exposure levels. In vivo pharmacodynamic research showed that mice treated with docetaxel-dihydroartemisinin nanoconjugates had lower systemic toxicity and higher survival ratio than those of control groups. This potential of nanoconjugates was developed as a novel nanoplateform to treat tumor. [ABSTRACT FROM AUTHOR]