Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

Preparation and Characterization of Nanocrystalline CeO_2 by Precipitation Method

CeO 2 nanocrystalline particulates with different sizes were prepared by precipitation method using ethanol as dispersive and protective reagent. XRD spectra show that the synthesized CeO 2 has cubic crystalline structure of space group O 5 H-F M3M, when calcination temperature is in the range of 250～800 ℃. TEM images reveal that CeO 2 particles are spherical in shape. The average size of the particles increases with the increase of calcination temperature. Thermogravimetric analysis indicates that the weight loss of precursor mainly depends on the calcination temperature, and little depends on the calcination time. Measurements of CeO 2 relative density show that the relative density of CeO 2 nanocrystalline powders increases with increasing CeO 2 particle size.

Preparation of gold nanoparticles supported on Nb_2O_5 by deposition precipitation and deposition reduction methods and their catalytic activity for CO oxidation

Nanoparticulate gold catalysts supported on niobium oxides （Nb2O5） were prepared by different deposition methods. The deposition precipitation （DP） method, DP method with urea, deposition reduction （DR） method and one‐pot method were used to prepare a 1 wt%Au/Nb2O5 catalyst. Lay‐ered‐type Nb2O5 synthesized by a hydrothermal method （Nb2O5（HT）） was the most suitable as a support among various types of Nb2O5 including commercially available Nb2O5 samples. It appeared that the large BET surface area of Nb2O5（HT） enabled the dispersion of gold as nanoparticles （NPs）. Gold NPs with a mean diameter of about 5 nm were deposited by both the DP method and DR method on Nb2O5（HT） under an optimized condition. The temperature for 50%CO conversion for Au/Nb2O5（HT） prepared by the DR method was 73 ＆#176;C. Without deposition of gold, Nb2O5（HT） showed no catalytic activity for CO oxidation even at 250 ＆#176;C. Therefore, the enhancement of the activity by deposition of gold was remarkable. This simple Au/Nb2O5 catalyst will expand the types of gold catalysts to acidic supports, giving rise to new applications.

In situ apolipoprotein E-enriched corona guides dihydroartemisinin-decorating nanoparticles towards LDLr-mediated tumor-homing chemotherapy

The therapeutic efficiency of active targeting nanoparticulate drug delivery systems(nano-DDS)is highly compromised by the plasma proteins adsorption on nanoparticles(NPs)surface,which significantly hinders cell membrane receptors to recognize the designed ligands,and provokes the off-target toxicity and rapid clearance of NPs in vivo.Herein,we report a novel dihydroartemisinin(DHA)-decorating nano-DDS that in situ specifically recruits endogenous apolipoprotein E(apoE)on the NPs surface.The apoE-anchored corona is able to prolong PLGA-PEG2000-DHA(PPD)NPs circulation capability in blood,facilitate NPs accumulating in tumor cells by the passive enhanced permeability and retention(EPR)effect and low-density lipoprotein receptor(LDLr)-mediated target transport,and ultimately improve the in vivo antitumor activity.Our findings demonstrate that the strategy of in situ regulated apoE-enriched corona ensures NPs an efficient LDLr-mediated tumor-homing chemotherapy.

Effects of rapid solidification on the microstructure and microhardness of a lead-free Sn-3.5Ag solder

A lead-free Sn-3.5Ag solder was prepared by rapid solidification technology. The high solidification rate, obtained by rapid cooling, promotes nucleation, and suppresses the growth of Ag3Sn intermetallic compounds （IMCs） in Ag-rich zone, yielding fine Ag3Sn nanoparticulates with spherical morphology in the matrix of the solder. The large amount of tough homogeneously-dispersed IMCs helps to improve the surface area per unit volume and obstructs the dislocation lines passing through the solder, which fits with the dispersion-strengthening theory. Hence, the rapidly-solidified Sn-3.5Ag solder exhibits a higher rnicrohardness when compared with a slowly-solidified Sn-3.5Ag solder.

Preparation of Nanocrystalline ZrO_2 by Reverse Precipitation Method

Nanncrystalline ZrO2 particulates with different sizes were prepared by precipitation method using ethanol as dispersive and protective reagent. XRD patterns show that the synthesized ZrO2 is monnclinic in structure with space group P21/a when calcination temperature is in the range of 400- 1000 ℃ . It is found that the smaller the particle, the bigger the crystal lattice distortion, the worse the costal growth, and the lower the diffrnction intensity. TEM images reveal that ZrO2 particles are spherical in shape, and the particle size distribution is in narrow range. The mean sizes of the particles increase with the increase of calcination temperatures . It is first to observe tbe streaks of different crystallographic planes. Thermogravimetric analysis indicates that the crystallization temperature of ZrO2 is 461.32 ℃ . Measurement of ZrO2 relative density shows that the relative density of nanocrystalline ZrO2 powders increases witb the increasing of ZrO2 particle sizes.

A review of research on nanoparticulate flow undergoing coagulation

Nanoparticulate flows occur in a wide range of natural phenomena and engineering applications and, hence, have attracted much attention. The purpose of the present paper is to provide a review of the research conducted over the last decade. The research covered relates to the Brownian coagulation of monodisperse and polydisperse particles, the Taylor-series expansion method of moment, and nanoparticle distributions due to coagulation in pipe and channel flow, jet flow, and the mixing layer and in the process of flame synthesis and deposition.

Leukocyte-derived biomimetic nanoparticulate drug delivery systems for cancer therapy

Precise drug delivery to tumors with low system toxicity is one of the most important and challenging tasks for pharmaceutical researchers. Despite progress in the field of nanotherapeutics, the use of artificially synthesized nanocarriers still faces several challenges, including rapid clearance from blood circulation and limited capability of overcoming multiple physiological barriers, which hamper the clinical application of nanoparticle-based therapies. Since leukocytes(including monocytes/macrophages,neutrophils, dendritic cells and lymphocytes) target tumors and can migrate across physiological barriers,leukocytes are increasing utilized as carriers to transfer nanoparticles to tumors. In this review we specifically focus on the molecular and cellular mechanisms of leukocytes that can be exploited as a vehicle to deliver nanoparticles to tumors and summarize the latest research on how leukocytes can be harnessed to improve therapeutic end-points. We also discuss the challenges and opportunities of this leukocyte-derived nanoparticle drug delivery system.

One-pot Synthesis of PEGylated Gd-based Nanoparticles as High-performance and Biocompatibility Contrast Agents for T1-Weighted Magnetic Resonance Imaging In vivo

Polyethylene glycol modified(PEGylated) NaGdF4(PEG-NaGdF4) nanoparticles as a novel T1-weighted magnetic resonance imaging(MRI) contrast agent was successfully constructed by a one-pot hydrothermal synthesis method. Because of the functionalization of PEG, the nanoprobes had excellent dispersity, excellent stability and high biocompatibility. More importantly, the as-prepared PEG-NaGdF4 nanoprobes revealed the high longitudinal relaxivity value and prominent -weighted MRI contrast performance, which was superior to the commercial MRI contrast agents. With the facile synthesis, excellent dispersity, outstanding stability, remarkable contrast performance and high biocompatibility, the PEGylated NaGdF4 nanoparticles brought more opportunities to the new generation of nanoparticulate-based T1-weighted MRI contrast agents in clinic.

Polyurethane scaffold-based 3D lung cancer model recapitulates in vivo tumor biological behavior for nanoparticulate drug screening

Lung cancer is the leading cause of cancer mortality worldwide.Preclinical studies in lung cancer hold the promise of screening for effective antitumor agents,but mechanistic studies and drug discovery based on 2D cell models have a high failure rate in getting to the clinic.Thus,there is an urgent need to explore more reliable and effective in vitro lung cancer models.Here,we prepared a series of three-dimensional(3D)waterborne biodegradable polyurethane(WBPU)scaffolds as substrates to establish biomimetic tumor models in vitro.These 3D WBPU scaffolds were porous and could absorb large amounts of free water,facilitating the exchange of substances(nutrients and metabolic waste)and cell growth.The scaffolds at wet state could simulate the mechanics(elastic modulus∼1.9 kPa)and morphology(porous structures)of lung tissue and exhibit good biocompatibility.A549 lung cancer cells showed adherent growth pattern and rapidly formed 3D spheroids on WBPU scaffolds.Our results showed that the scaffold-based 3D lung cancer model promoted the expression of anti-apoptotic and epithelial-mesenchymal transition-related genes,giving it a more moderate growth and adhesion pattern compared to 2D cells.In addition,WBPU scaffold-established 3D lung cancer model revealed a closer expression of proteins to in vivo tumor,including tumor stem cell markers,cell proliferation,apoptosis,invasion and tumor resistance proteins.Based on these features,we further demonstrated that the 3D lung cancer model established by the WBPU scaffold was very similar to the in vivo tumor in terms of both resistance and tolerance to nanoparticulate drugs.Taken together,WBPU scaffold-based lung cancer model could better mimic the growth,microenvironment and drug response of tumor in vivo.This emerging 3D culture system holds promise to shorten the formulation cycle of individualized treatments and reduce the use of animals while providing valid research data for clinical trials.

On the nanoparticulate flow

Nanoparticulate flows occur in a wide range of natural and engineering applications hence have received much attention. The purpose of the present paper is to provide a brief review on the research on the nanoparticulate flow in some aspects which consist of the method of moment for solving the particle population balance equation, penetration efficiency, pressure drop and heat transfer in the turbulent nanoparticulate pipe flow, fluctuating-lattice Boltzrnann model for Brownian motion of nanoparticles.