Dongmei Sun

pH-sensitive strontium carbonate nanoparticles as new anticancer vehicles for controlled etoposide release

Strontium carbonate nanoparticles (SCNs), a novel biodegradable nanosystem for the pH-sensitive release of anticancer drugs, were developed via a facile mixed solvent method aimed at creating smart drug delivery in acidic conditions, particularly in tumor environments. Structural characterization of SCNs revealed that the engineered nanocarriers were uniform in size and presented a dumbbell-shaped morphology with a dense mass of a scale-like spine coating, which could serve as the storage structure for hydrophobic drugs. Chosen as a model anticancer agent, etoposide was effectively loaded into SCNs based on a simultaneous process that allowed for the formation of the nanocarriers and for drug storage to be accomplished in a single step. The etoposide-loaded SCNs (ESCNs) possess both a high loading capacity and efficient encapsulation. It was found that the cumulative release of etoposide from ESCNs is acid-dependent, and that the release rate is slow at a pH of 7.4; this rate increases significantly at low pH levels (5.8, 3.0). Meanwhile, it was also found that the blank SCNs were almost nontoxic to normal cells, and ESCN systems were evidently more potent in antitumor activity compared with free etoposide, as confirmed by a cytotoxicity test using an MTT assay and an apoptosis test with fluorescence-activated cell sorter (FACS) analysis. These findings suggest that SCNs hold tremendous promise in the areas of controlled drug delivery and targeted cancer therapy.

Preparation of hierarchical mesoporous CaCO3 by a facile binary solvent approach as anticancer drug carrier for etoposide.

To develop a nontoxic system for targeting therapy, a new highly ordered hierarchical mesoporous calcium carbonate nanospheres (CCNSs) as small drug carriers has been synthesized by a mild and facile binary solvent approach under the normal temperature and pressure. The hierarchical structure by multistage self-assembled strategy was confirmed by TEM and SEM, and a possible formation process was proposed. Due to the large fraction of voids inside the nanospheres which provides space for physical absorption, the CCNSs can stably encapsulate the anticancer drug etoposide with the drug loading efficiency as high as 39.7 wt.%, and etoposide-loaded CCNS (ECCNS) nanoparticles can dispersed well in the cell culture. Besides, the drug release behavior investigated at three different pH values showed that the release of etoposide from CCNSs was pH-sensitive. MTT assay showed that compared with free etoposide, ECCNSs exhibited a higher cell inhibition ratio against SGC-7901 cells and also decreased the toxicity of etoposide to HEK 293 T cells. The CLSM image showed that ECCNSs exhibited a high efficiency of intracellular delivery, especially in nuclear invasion. The apoptosis test revealed that etoposide entrapped in CCNSs could enhance the delivery efficiencies of drug to achieve an improved inhibition effect on cell growth. These results clearly implied that the CCNSs are a promising drug delivery system for etoposide in cancer therapy.

High-energy pulse-electron-beam-induced molecular and cellular damage in Saccharomyces cerevisiae

The high-energy pulse electron beam (HEPE) is a new method for mutation breeding. Previously, we demonstrated that HEPE radiation improved thermotolerance and ethanol production of Saccharomyces cerevisiae. To investigate the influence of HEPE on yeast molecular and cellular damage, cells were separately treated with HEPE radiation at different doses (0, 200, 400, 600, 800, 1000, 1200 and 1400 Gy). Based on results obtained, protein leakage and diffusion of intracellular nucleotide and propidium iodide (PI) uptake assays showed that HEPE clearly enhanced the cell membrane permeability of yeast depending on the dose of exposure. Yeast cells treated with HEPE radiation had significantly elevated levels of DNA instability, as detected by the chromosome spreading assay. These results correlated well with the measurement of increased levels of chromosomal aberrations and apoptosis. Intracellular reactive oxygen species (ROS) and caspase 3 activity were also measured in HEPE-applied yeast cells. Caspase 3 appeared to be involved in HEPE-induced apoptosis. Use of dihydroethidium staining and confocal laser scanning microscopy (CLSM) showed increased levels of intracellular ROS as a consequence of augmented pulsing. Moreover, yeast cells retained some photoreactivation capacity when the dose of HEPE exposure was less than 600 Gy. Thereafter, the level of damage was too serious to repair. Thus, photoreactivation had a repair effect upon HEPE radiation-induced damage. The results of our studies provide a possible explanation for the molecular and cellular effects of HEPE radiation upon S. cerevisiae.

Synthesis of CaCO3 Nanobelts for Drug Delivery in Cancer Therapy

Nanobelt carriers have demonstrated some advantages such as good biocompatibility, biodegradability, and strain-accommodating properties. We prepared an optimized nanobelt carrier formulation for drug (etoposide) as an oral delivery system and estimated the potential of calcium carbonate (CaCO3) nanobelts. The nanobelts were prepared by the method of binary solvent approach and were characterized by transmission electron microscope (TEM), scanning electron microscopy (SEM), and ultraviolet–visible (UV–vis) spectra. MTT (3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide) assay test exhibited that etoposide-loaded calcium carbonate nanobelts (ECCNBs) showed a higher cell kill ratio against SGC-7901 cells compared with free drug. The apoptosis test and cell cycle test analysis revealed that etoposide entrapped in calcium carbonate nanobelts (CCNBs) could enhance the delivery efficiencies of drug and improved inhibition effect. The present findings demonstrated that ECCNBs might induce cell cycle arrest at G2/M phase and cell apoptosis in a p53-related manner. It can be foreseen that CCNBs are a promising drug carrier to store the anti-cancer drug for cancer therapy and drug delivery.

Photoionization of Oxidized Coenzyme Q in Microemulsion: Laser Flash Photolysis Study in Biomembrane‐like System

Photoexcitation to generate triplet state has been proved to be the main photoreaction in homogeneous system for many benzoquinone derivatives, including oxidized coenzyme Q (CoQ) and its analogs. In the present study, microemulsion of CoQ, a heterogeneous system, is employed to mimic the distribution of CoQ in biomembrane. The photochemistry of CoQ10 in microemulsion and cyclohexane is investigated and compared using laser flash photolysis and results show that CoQ10 undergoes photoionization via a monophotonic process to generate radical cation of CoQ10 in microemulsion and photoexcitation to generate excited triplet state in cyclohexane. Meanwhile, photoreactions of duroquinone (DQ) and CoQ0 in microemulsion are also investigated to analyze the influence of molecular structure on the photochemistry of benzoquinone derivatives in microemulsion. Results suggest that photoexcitation, which is followed by excited state‐involved hydrogen‐abstraction reaction, is the main photoreaction for DQ and CoQ0 in microemulsion. However, photoexcited CoQ0 also leads to the formation of hydrated electrons. The isoprenoid side chain‐involved high resonance stabilization is proposed to explain the difference in photoreactions of CoQ0 and CoQ10 in microemulsion. Considering that microemulsion is close to biomembrane system, its photoionization in microemulsion may be helpful to understand the real photochemistry of biological quinones in biomembrane system.

Interaction of Retinoic Acid Radical Cation with Lysozyme and Antioxidants: Laser Flash Photolysis Study in Microemulsion

All‐trans retinoic acid (ATRA) plays essential roles in the normal biological processes and the treatment of cancer and skin diseases. Considering its photosensitive property, many studies have been focused on the photochemistry of ATRA. In this study, we investigated the transient phenomena in the laser flash photolysis (LFP) of ATRA in microemulsion to further understand the photochemistry of ATRA. Results show that 355 nm LFP of ATRA in both acidic and alkaline conditions leads to the generation of retinoic acid cation radicals (ATRA•+) via biphotonic processes. The employment of microemulsion system allows us to investigate the reaction of hydrophobic ATRA•+ with molecules of different polarity. Therefore, we studied the reaction activity of ATRA•+ to many hydrophobic and hydrophilic molecules. Results show that ATRA•+ can efficiently interact with lysozyme, tyrosine, tryptophan and many antioxidants, such as curcumin (Cur), vitamin C (VC) and gallic acid (GA). The apparent rate constants of these reactions were measured and compared. These findings suggest that ATRA•+ is a reactive transient product which may pose damage to lysozyme, and antioxidants, such as Cur, VC and GA, may inactivate ATRA•+ by efficient quenching reactions.