Vanadium Oxide Nanozymes with Multiple Enzyme-Mimic Activities for Tumor Catalytic Therapy.

Using tumors containing high concentrations of hydrogen peroxide to design nanozymes is a new and effective strategy, and vanadium-based nanomaterials receive increasing attention. In this paper, four kinds of vanadium oxide nanozymes with different valences of vanadium are synthesized by a simple method to verify the effect of valence on enzyme activity. Vanadium oxide nanozyme-III (Vnps-III) with a low valence of vanadium (V4+) exhibits good peroxidase (POD) and oxidase (OXD) activities, which can effectively produce reactive oxygen species (ROS) in the tumor microenvironment for tumor treatment. In addition, Vnps-III can also consume glutathione (GSH) to reduce ROS consumption. Vanadium oxide nanozyme-I (Vnps-I) containing a high valence of vanadium (V5+) has catalase (CAT) activity, which can catalyze hydrogen peroxide (H2O2) into oxygen (O2), which is beneficial to alleviate the hypoxic environment of solid tumors. Finally, a vanadium oxide nanozyme with both trienzyme simulation activity and GSH consumption ability was screened out by adjusting the ratio of V4+ to V5+ in vanadium oxide nanozymes. In cell and animal experiments, we successfully demonstrate that vanadium oxide nanozymes have excellent antitumor ability and high safety, which may bring great potential for clinical cancer treatment.

pH-Responsive Hyaluronic Acid Nanoparticles for Enhanced Triple Negative Breast Cancer Therapy.

Purpose: This study emphasized that dasatinib (DAS) and olaparib (OLA) have synergistic effects on triple negative breast cancer, by inducing DNA damage and inhibiting DNA damage repair. However, poor water solubility, short half-life of drugs, and low drug concentration in tumor tissue limit the clinical application. Methods: In this research, acid-sensitive ester bonds were used to connect hydrophobic DAS and hydrophilic hyaluronic acid (HA) to form the amphiphilic polymer prodrug HA-DAS, and then OLA was added as the core, the HA-DAS was used as the carrier to form nanomicelles (HDO-NPs) in aqueous. The characterization and drug release of HDO-NPs were studied, and the cytotoxicity, targeting effect, and intracellular transport behavior of HDO-NPs were evaluated in MDA-MB-231. In addition, the pharmacokinetic and therapeutic effect of HDO-NPs were further verified in vivo. Results: In vitro characterizations showed that HDO-NPs were spherical with uniform particle size, good stability and anti-dilution ability, and displayed favorable pH-responsive drug release behavior. In addition, the cell experiments showed that HDO-NPs could be effectively taken up by binding to the overexpressed CD44 proteins of MDA-MB-231 cells, resulting in increased intracellular drug concentration. In vivo experiments showed that HDO-NPs can effectively target tumor tissues, have excellent therapeutic effects on tumor, significantly prolong the circulation time of drugs in vivo, and effectively improved the bioavailability of drugs. Conclusion: DAS and OLA were designed into micelles, the efficacy of HDO-NPs was higher than that of free drugs. Therefore, HDO-NPs have good application prospects in the treatment of triple negative breast cancer.

Construction of pH-sensitive targeted micelle system co-delivery with curcumin and dasatinib and evaluation of anti-liver cancer.

Nanomedicine delivery systems can achieve precise drug delivery and reduce toxic side effects compared with traditional drug delivery methods, but further development is still needed to eliminate obstacles such as multiple drug co-delivery, uncontrolled drug-release, and drug-resistance. Herein, we designed a dual drug-loaded nanosystem (THCD-NPs) that selectively transports and targets tumor cells for the treatment of liver cancer. In this drug delivery system, hyaluronic acid (HA)-conjugated curcumin (Cur) and d-α-tocopherol acid polyethylene glycolsuccinate (TPGS) were used as selective drug-carrying vehicles to deliver dasatinib (DAS) to cancer cells for combined administration. The mean size of the nanoparticles was approximately 66.14 ± 4.02 nm with good in vitro stability. The nanoparticles were pH sensitive and could accelerate drug release at low pH conditions. In vitro experiments showed that THCD-NPs were significantly cytotoxic to HepG2 cells and could be effectively taken up by these cells. Detailed investigations also demonstrated its pro-apoptotic activity. In vivo NIR fluorescence imaging showed that the nanoparticles could accumulate efficiently at the tumor site. Meanwhile, in vivo experiments showed that THCD-NPs significantly inhibited tumor growth and reduced the toxic side effects of free drugs in a mouse solid tumor model. In short, the nanoparticles we prepared provide a new idea for the treatment of liver cancer.

A Combined Self-Assembled Drug Delivery for Effective Anti-Breast Cancer Therapy.

AIM: The metastasis of breast cancer is an important cause of tumor recurrence. This study highlights that tyrosine kinase inhibitors dasatinib (DAS) and rosiglitazone (ROZ) inhibit tumor growth and reduce the occurrence of tumor cell metastasis. Due to the poor water solubility, short half-time in the body of DAS and ROZ, which increases the difficulty of tumor treatment, as well as the demand for nano-drug delivery systems for organ-specific therapies. METHODS: Hyaluronic acid (HA) and DAS are bonded by a pH-sensitive ester bond to form an HA-DAS polymer. Then, ROZ was added as the core, D-A-tocopherol polydiethylene glycol isosuccinate (TPGS) and HA-DAS were used as carriers to form HA-DAS and TPGS mixed micelle system loaded with ROZ (THDR-NPs). The size and structure of THDR-NPs were characterized, the drug release, stability and biosafety of THDR-NPs were studied. In vitro, the cytotoxicity, targeting effect and tumor metastasis inhibition of THDR-NPs were evaluated in human breast cancer cell lines. In addition, the selective potency of designed THDR-NPs in depleting was further verified in vivo in the tumor-bearing nude mice model. RESULTS: The designed THDR-NPs have a particle size of less than 100 nm, good stability, biological safety and sustained release, and showed strong therapeutic effects on breast cancer models in vitro and in vivo. Moreover, it has been proved that THDR-NPs have the ability to inhibit tumor metastasis. CONCLUSION: DAS and ROZ were designed into micelles, the efficacy of THDR-NPs was higher than that of free drugs. These results indicate that nanoparticles have a good application prospect in the treatment of tumor metastasis.

Dasatinib self-assembled nanoparticles decorated with hyaluronic acid for targeted treatment of tumors to overcome multidrug resistance.

Multidrug resistance (MDR) and lack of targeting specificity are the main reasons why traditional drug therapies fail and produce toxic side effects in cancer chemotherapy. In order to increase targeting specificity and maximize therapeutic efficacy, new intelligent drug delivery systems are needed. In this study, we prepared the hyaluronic acid (HA) conjugated dasatinib (DAS) and D-α-tocopherol acid polyethylene glycolsuccinate (TPGS) copolymer nanoparticles (THD-NPs). The water solubility of the hydrophobic drug DAS was improved by chemically linking with HA. HA can bind to the over-expressed CD44 protein of tumor cells to increase targeting specificity, TPGS can inhibit the activity of P-glycoprotein (P-gp), and increase the intracellular accumulation of drugs. The prepared drug-loaded nanoparticle has a particle size of 82.23 ± 1.07 nm with good in vitro stability. Our in vitro studies showed that THD-NPs can be released more rapidly in a weakly acidic environment (pH = 5.5) than in a normal physiological environment (pH = 7.4), which can realize the selective release of nanoparticles in tumor cells. Compared to free drugs, THD-NPs showed more efficient cellular uptake, effectively increased the cytotoxic effect of DAS on nasopharyngeal carcinoma HNE1 cells drug resistance HNE1/DDP cells and increased the accumulation of drugs in HNE1/DDP cells, which may be due to the inhibitory effect of TPGS on the efflux function of P-gp. In vivo experiments showed that THD-NPs can effectively inhibit tumor growth without obvious side effects. In conclusion, the targeted and pH-sensitive nanosystem, we designed has great potential to overcome drug resistance and increase therapeutic effects in cancer treatment.

Bird diversity in northern Myanmar and conservation implications.

We conducted four bird biodiversity surveys in the Putao area of northern Myanmar from 2015 to 2017. Combined with anecdotal information collected between 2012 and 2015, we recorded 319 bird species, including two species (Arborophila mandellii and Lanius sphenocercus) previously unrecorded in Myanmar. Bulbuls (Pycnonotidae), babblers (Timaliidae), pigeons and doves (Columbidae), and pheasants and partridges (Phasianidae) were the most abundant groups of birds recorded. Species richness below 1 500 m a. s. l. was higher than species richness at higher elevations. Our results suggest that the current protected areas in this region should be expanded to lower elevations to cover critical conservation gaps.