A generic coordination assembly-enabled nanocoating of individual tumor cells for personalized immunotherapy

A generic and effective tumor cells encapsulation strategy enabled by metal–organic coordination is developed to prepare a vaccine for personalized immunotherapy. Specifically, an epigallocatechin‐3‐gallate (EGCG)‐Al(III) coordination layer is in situ formed onto individual living cells in aqueous phase and the process can be completed within an hour. 98% of proteins in the cells are entrapped within the microparticles, which are endowed with high antigens loading capacity. The microparticles enhance the uptake efficiency of antigens, protect antigens from degradation in vivo, and delay the retention time of antigens in the lymph nodes. Moreover, dendritic cells (DCs) activation is triggered by the microparticles, and simultaneously, the expression of costimulation marker on DCs and the production of Th1‐related cytokines are significantly upregulated. Moreover, six kinds of tumor cells are utilized and successfully coated with the EGCG/Al(III) layer, suggesting the generalization of this strategy. More importantly, the microparticles exhibit a comparative antitumor effect with polyinosinic–polycytidylic acid (PolyI:C) in B16 pulmonary metastasis model. Overall, the encapsulation strategy enabled by metal–organic coordination can be potentially useful for personalized immunotherapy customized to individual patient's tumor cells

A Novel Docetaxel-Loaded Poly (ε-Caprolactone)/Pluronic F68 Nanoparticle Overcoming Multidrug Resistance for Breast Cancer Treatment

Multidrug resistance (MDR) in tumor cells is a significant obstacle to the success of chemotherapy in many cancers. The purpose of this research is to test the possibility of docetaxel-loaded poly (ε-caprolactone)/Pluronic F68 (PCL/Pluronic F68) nanoparticles to overcome MDR in docetaxel-resistance human breast cancer cell line. Docetaxel-loaded nanoparticles were prepared by modified solvent displacement method using commercial PCL and self-synthesized PCL/Pluronic F68, respectively. PCL/Pluronic F68 nanoparticles were found to be of spherical shape with a rough and porous surface. The nanoparticles had an average size of around 200 nm with a narrow size distribution. The in vitro drug release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake of PCL/Pluronic F68 nanoparticles in docetaxel-resistance human breast cancer cell line, MCF-7 TAX30, when compared with PCL nanoparticles. The cytotoxicity of PCL nanoparticles was higher than commercial Taxotere®in the MCF-7 TAX30 cell culture, but the differences were not significant (p > 0.05). However, the PCL/Pluronic F68 nanoparticles achieved significantly higher level of cytotoxicity than both of PCL nanoparticles and Taxotere®(p < 0.05), indicating docetaxel-loaded PCL/Pluronic F68 nanoparticles could overcome multidrug resistance in human breast cancer cells and therefore have considerable potential for treatment of breast cancer

Analysis of the role of vaccine adjuvants in modulating dendritic cell activation and antigen presentation in vitro

We have studied the effects of adjuvant formulations on the activation and antigen-presenting functions of bone marrow-derived dendritic cells (DCs). While LPS could induce high-level expression of MHC Class II and co-stimulator molecules on DCs, it did not enhance antigen presentation to co-stimulation independent DO11.GFP T hybridoma cells. In contrast, alum, NISV and PLGA formulations failed to activate DCs, but NISV and PLGA could enhance antigen-presentation efficiency by 10–100-fold. Irrespective of the previously described antigen release characteristics of each adjuvant, antigen presentation peaked at 6 h and waned thereafter for all formulations. Given the importance of DCs in the activation of naı&#x0308;ve T cell responses, these studies suggest that as yet undefined pathways of DC activation in vivo may underlie the activity of alum, PLGA and NISV adjuvants. Furthermore, as NISV and PLGA do not appear to act as slow-release systems in DCs, the ability of these particulate systems to induce high levels of antigen presentation by DCs probably has a more significant role in their adjuvant activity

Investigation on the Evolution of Nano-Scale Defects of CL-20 Crystals under Thermal Treatment by Wide/Small-Angle X-ray Scattering

Nano-scale crystal defects extremely affect the security and reliability of the explosive charges of weapons. In order to understand the evolution of nano-scale defects of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaaza-isowurtzitane (CL-20) explosive crystals under thermal treatments, the specific surface, volume fraction and size distribution of the nano-scale defects were studied by using Wide Angle X-ray Scattering (WAXS) and Small Angle X-ray Scattering (SAXS) during the temperature range from 30 &deg;C to 200 &deg;C. The results showed that the number and size of the pores in CL-20 powder did not change significantly during the heating process before phase transformation (30&ndash;160 &deg;C). At 170 &deg;C, CL-20 began to convert from &epsilon;- to &gamma;- phase, and the specific surface and volume fraction of the nano-scale defects increased significantly. Further investigation of the pore size distribution showed that the number of pores with a small size (radius 9&ndash;21 nm) changed particularly significantly, resulting from the cracking of the CL-20 crystal powder during phase transition. At 200 &deg;C, the phase transition was completed and &gamma;-CL-20 was created, and the small-sized pores gradually grew into medium-sized (radius 21&ndash;52 nm) pores over time when the temperature was fixed at 200 &deg;C

Characterization of Crystal Microstructure Based on Small Angle X-ray Scattering (SAXS) Technique

Small-angle X-ray scattering (SAXS) is an effective method to obtain microstructural information of materials. However, due to the influence of crystal surface effects, SAXS has a deviation in the characterization of the crystal microstructure. In order to solve the influence of crystal surface effect on the internal defect signal, the microstructure of Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) crystal was characterized by soaking the sample in the matching solution. We found that the absolute scattering intensity, specific surface and volume fraction of the sample in the matching solution are significantly lower than the initial sample, which solves the influence of the crystal surface effect on the test results. Comparing the scattering results of the samples in different electron density matching solutions, it was found that the best result was obtained when using GPL-107 perfluoropolyether (PFPE) matching solution and the same law was obtained by controlling the experiment with 2,4,6,8,10,12-hexanitrohexaazaisowurtzitane (CL-20) crystal. The fitting density was calculated according to the theoretical density and void volume fraction of the sample, and the calculated results are close to the test results of Particle Density Distribution Analyzer (PDDA). Based on this paper, we provide a method to obtain the correct information of crystal microstructure

PNP-Ligated Rare-Earth Metal Catalysts for Efficient Polymerization of Isoprene

The tridentate PNP ligand-supported rare-earth metal complexes, i.e., bis[o-diphenylphosphinophenyl]amido-Re-bis[o-dimethylaminobenzyl], [(Ph2P-o-C6H4)2N]Re[(CH2-o-Me2N(C6H4))2]: (Re = Y, 1; Nd, 2; Gd, 3) were applied to isoprene polymerization. When activated with borate activator ([PhMe2NH][B(C6F5)4] (NH-BARF), catalysts 1 and 3 exhibited excellent catalytic efficiency in aromatic media, produced very-high to ultrahigh molecular weight (Mw over 130 × 104 g/moL) polyisoprene rubber (PIR), and the obtained PIR contained over 98% cis-1,4 head-to-tail repeating unites. In most cases, the borate-activated polymerization reaction proceeded in a quasi-living pattern (PDI = 1.2–1.5) under controlled monomer conversion; whereas, activated with the commercially available modified methylaluminoxane (MMAO3A) in aliphatic hydrocarbon media, complexes 1, 2 and 3 all showed high catalytic efficiency, produced high molecular weight PIR with narrow molecular weight distribution (PDI ≤ 2.0) and high cis-1,4 head-to tail repeating unites in the range of 91–95%. Thus, the catalyst systems that consisted of 1, 2 and 3/MMAO3A, are closely relevant to the current industrial polybutadiene rubber (PBR) and PIR production processes

Micelle or polymersome formation by PCL-PEG-PCL copolymers as drug delivery systems

Poly(8-caprolactone)-b-poly(ethylene glycol)-b-poly(e-caprolactone) (PCL-b-PEG-b-PCL, PCEC) triblock copolymers have been widely investigated in last several decades. Here, by altering the weight ratio of monomers in ring-opening polymerization, a series of PCEC triblock copolymers with varying hydrophobicity were synthesized, which were characterized by FTIR, H-1 NMR, GPC and DSC. When PCEC copolymers with different weight ratios of PCL/PEG were dispersed in different aqueous solutions, they could self-assemble and form two distinctive nanoparticular structures: micelles or polymersomes. We then chose paclitaxel (PTX) as the model drug and encapsulate PTX into PCEC polymeric micelles and polymersomes. The physicochemical characterizations of the nanoparticles such as morphology, the size and distribution, zeta potential, drug loading content, and encapsulation efficiency were also performed. Our results showed that polymeric micelles or polymersomes from PCEC both displayed narrow size distributions and could achieve high drug loading efficiencies. In vitro cellular uptake results suggested that Nile Red loaded polymeric micelles or polymersomes displayed more internalization after 24 h incubation than those after 4h incubation. These findings suggest that polymeric micelles and polymersomes based on PCL-b-PEG-b-PCL copolymers have great potential to effectively delivery hydrophobic drugs. (C) 2017 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved