Shape regulated anticancer activities and systematic toxicities of drug nanocrystals in vivo

Zhou, Mengjiao; Zhang, Shun; Yu, Caitong; Nan, Xueyan; Chen, Xianfeng

doi:10.1016/j.nano.2015.09.006

Cited by 37 publications

(19 citation statements)

References 26 publications

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“…Aside from the effects of crystal size and phase on cell injury 6 , 7 , crystal shape also exerts different effects on cell injury. Previous studies about the effect of crystal shape on cytotoxicity mainly focused on spherical or rod-shaped particles 9 , 19 . Crystal planes do not differ in spherical particles, but most crystals formed in vivo are polyhedron structures.…”

Section: Discussionmentioning

confidence: 99%

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Shape-dependent cellular toxicity on renal epithelial cells and stone risk of calcium oxalate dihydrate crystals

Sun

Ouyang

2017

Sci Rep

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Renal epithelial cell injury causes crystal retention and leads to renal stone formation. However, the effects of crystal shape on cell injury and stone risk remain unclear. This study compared the cytotoxicity degrees of calcium oxalate dihydrate (COD) crystals having different shapes toward human kidney proximal tubular epithelial (HK-2) cells to reveal the effect of crystal shape on cell injury and to elucidate the pathological mechanism of calcium oxalate kidney stones. The effects of exposure to cross-shaped (COD-CS), flower-like (COD-FL), bipyramid (COD-BD), and elongated–bipyramid (COD-EBD) COD crystals on HK-2 cells were investigated by examining the cell viability, cell membrane integrity, cell morphology change, intracellular reactive oxygen species, mitochondrial membrane potential (Δψm), and apoptotic and/or necrotic rate. Crystals with large (100) faces (COD-EBD) and sharp edges (COD-CS) showed higher toxicity than COD-BD and COD-FL, respectively. COD crystal exposure caused cell membrane rupture, upregulated intracellular reactive oxygen, and decreased Δψm. This series of phenomena ultimately led to a high apoptotic rate and a low necrotic rate. Crystals with large active faces have a large contact area with epithelial cell surface, and crystals with sharp edges can easily scratch epithelial cells; these factors could promote crystal adhesion and aggregation, thus increasing stone risk.

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Section: Discussionmentioning

confidence: 99%

“…The shape of exogenous particles is an important parameter influencing their biological safety and application 9 – 12 . For instance, a study conducted on zebrafish embryos found that 30, 60, and 100 nm spherical nickel nanoparticles are less toxic than 60 nm dendritic clusters.…”

Section: Introductionmentioning

confidence: 99%

Shape-dependent cellular toxicity on renal epithelial cells and stone risk of calcium oxalate dihydrate crystals

Sun

Ouyang

2017

Sci Rep

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“…At present, research about paclitaxel dosage forms include liposomes, 4,5 polymeric micelles or nanoparticles, 6,7 nanocrystallines, [8][9][10][11] mesoporous materials inclusion, [12][13][14] and so on. The use of paclitaxel nanoparticles as a potential dosage form has attracted the attention of researchers.…”

Section: Introductionmentioning

confidence: 99%

Pure paclitaxel nanoparticles: preparation, characterization, and antitumor effect for human liver cancer SMMC-7721 cells

Gao

Liu

et al. 2018

IJN

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IntroductionPure paclitaxel nanoparticles (PPN), consisting entirely of drug molecules, were prepared by the electrostatic spraying method as promising candidates for antitumor application. Compared with the traditional preparation method, the advantage of the electrostatic spraying method included high production rates, relatively small particle sizes, and ease of preparation.Materials and methodsPaclitaxel was used to prepared PPN by electrostatic spray. The electrostatic spray device included a constant speed pump with a syringe, a high-voltage power supply, and a metal foil receiver was used to prepare and evaluate PPN. The syringe drew off a certain amount of paclitaxel chloroform solution (150 μg/mL) and was placed on the constant speed injection pump. The dissolution behavior of PPN was evaluated by dissolution test and the presence of paclitaxel in PPN was detected by X-Ray powder diffraction and differential scanning calorimetry. Effect of PPN on SMMC-7721 cells were studied by cell uptake, cell apoptosis and antitumor study.ResultsThe results of X-ray powder diffraction and differential scanning calorimetry characterization showed that the PPN were in an amorphous state. A dissolution study indicated that PPN have a significantly enhanced dissolution rate of paclitaxel. Moreover, SMMC-7721 tumor cells treated with PPN exhibited a distinctly high uptake rate that promoted cell apoptosis. An in vivo antitumor study demonstrated that PPN had significant antitumor efficacy.ConclusionAll conclusions verified that electrostatic spraying is a potential technology for developing PPN, and PPN can be regarded as a promising treatment for cancer.

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“…Table 1, Gal(oct)-C-MEs administration brought about a significant increase in white blood cells and platelets, offering a feasibility of combination therapy with chemotherapeutics. 17,32,33 As for the influence on the immune function, the concentrations of cytokines were also detected. As shown in Table 2, treatment with microemulsion did not reduce the serum concentration of tumor necrosis factor-α and interleukin-6 significantly.…”

Section: Safety Evaluationmentioning

confidence: 99%

Octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components to enhance tumor targeting and hepatoma therapy

Qu¹,

Liu²,

Huang³

et al. 2017

IJN

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A nanosized drug delivery platform with a combination of rational components and tumor targeting is significant for enhancement of anticancer therapy and reduction of side effects. In this study, we developed a octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components (Gal(oct)-C-MEs), which improved the tumor accumulation through asialoglycoprotein receptor-mediated endocytosis and promoted the antitumor efficacy through multicomponent-mediated synergistic effect. Octanoyl galactose ester (Gal(oct)) with a yield of 82.3% was synthesized through a green enzymatic reaction and multidimensional characterization. Gal(oct)-C-MEs with a spherical shape had a small and uniform particle size (58.49±1.03 nm), narrow polydispersity index (0.09±0.01) and neutral surface charge (−5.82±0.57 mV). In the cellular uptake studies, the internalized Gal(oct)-C-ME was 2.28-fold higher relative to that of coix seed component-based microemulsions (C-MEs). The half-maximal inhibitory concentration of Gal(oct)-C-MEs against HepG2 cells was 46.5±2.4 μg/mL, which was notably higher than that of C-MEs. Importantly, the intratumor fluorescence of HepG2 xenograft-bearing nude mice treated with Cy5/Gal(oct)-C-MEs was 1.9-fold higher relative to treatment with Cy5/C-MEs. In the study of antitumor efficacy in vivo, HepG2 xenograft-bearing nude mice intragastrically administered Gal(oct)-C-MEs for 14 days exhibited the strongest inhibition of tumor growth and the lowest toxicity against liver and kidney among all the treatments. In summary, Gal(oct)-C-ME, as a highly effective and safe anticancer drug delivery system, showed promising potential for hepatoma therapy.

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Shape regulated anticancer activities and systematic toxicities of drug nanocrystals in vivo

Cited by 37 publications

References 26 publications

Shape-dependent cellular toxicity on renal epithelial cells and stone risk of calcium oxalate dihydrate crystals

Shape-dependent cellular toxicity on renal epithelial cells and stone risk of calcium oxalate dihydrate crystals

Pure paclitaxel nanoparticles: preparation, characterization, and antitumor effect for human liver cancer SMMC-7721 cells

Octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components to enhance tumor targeting and hepatoma therapy

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