Stimuli-Responsive Polymeric Nanomaterials for the Delivery of Immunotherapy Moieties: Antigens,Adjuvants and Agonists

Immunotherapy has been investigated for decades, and it has provided promising results in preclinical studies. The most important issue that hinders researchers from advancing to clinical studies is the delivery system for immunotherapy agents, such as antigens, adjuvants and agonists, and the activation of these agents at the tumour site. Polymers are among the most versatile materials for a variety of treatments and diagnostics, and some polymers are reactive to either endogenous or exogenous stimuli. Utilizing this advantage, researchers have been developing novel and effective polymeric nanomaterials that can deliver immunotherapeutic moieties. In this review, we summarized recent works on stimuli-responsive polymeric nanomaterials that deliver antigens, adjuvants and agonists to tumours for immunotherapy purposes.     

The Effect of Oxidative Stress and Memantine-Incorporated Reactive Oxygen Species-Sensitive Nanoparticles on the Expression of N-Methyl-d-aspartate Receptor Subunit 1 in Brain Cancer Cells for Alzheimer’s Disease Application

The aim of this study is to fabricate reactive oxygen species (ROS)-sensitive nanoparticles composed of succinyl β-cyclodextrin (bCDsu), memantine and thioketal linkages for application in Alzheimer’s disease, and to investigate the suppression of N-methyl-d-aspartate (NMDA) receptor 1 (NMDAR1) in cells. Thioketal diamine was attached to the carboxyl group of bCDsu to produce thioketal-decorated bCDsu conjugates (bCDsu-thioketal conjugates) and memantine was conjugated with thioketal dicarboxylic acid (memantine-thioketal carboxylic acid conjugates). Memantine-thioketal carboxylic acid conjugates were attached to bCDsu-thioketal conjugates to produce bCDsu-thioketal-memantine (bCDsuMema) conjugates. SH-SY5Y neuroblastoma cells and U87MG cells were used for NMDAR1 protein expression and cellular oxidative stress. Nanoparticles of bCDsuMema conjugates were prepared by means of a dialysis procedure. Nanoparticles of bCDsuMema conjugates had small particle sizes less than 100 nm and their morphology was found to be spherical in transmission electron microscopy observations (TEM). Nanoparticles of bCDsuMema conjugates responded to H₂O₂ and disintegrated or swelled in aqueous solution. Then, the nanoparticles rapidly released memantine according to the concentration of H₂O₂. In an in vivo animal imaging study, thioketal-decorated nanoparticles labelled with fluorescent dye such as chlorin e6 (Ce6) showed that the fluorescence intensity was stronger in the brain than in other organs, indicating that bCDsuMema nanoparticles can efficiently target the brain. When cells were exposed to H₂O₂, the viability of cells was time-dependently decreased. Memantine or bCDsuMema nanoparticles did not practically affect the viability of the cells. Furthermore, a western blot assay showed that the oxidative stress produced in cells using H₂O₂ increased the expression of NMDAR1 protein in both SH-SY5Y and U87MG cells. Memantine or bCDsuMema nanoparticles efficiently suppressed the NMDAR1 protein, which is deeply associated with Alzheimer’s disease. Fluorescence microscopy also showed that H₂O₂ treatment induced green fluorescence intensity, which represents intracellular ROS levels. Furthermore, H₂O₂ treatment increased the red fluorescence intensity, which represents the NMDAR1 protein, i.e., oxidative stress increases the expression of NMDAR1 protein level in both SH-SY5Y and U87MG cells. When memantine or bCDsuMema nanoparticles were treated in cells, the oxidative stress-mediated expression of NMDAR1 protein in cells was significantly decreased, indicating that bCDsuMema nanoparticles have the capacity to suppress NMDAR1 expression in brain cells, which has relevance in terms of applications in Alzheimer’s disease.     

Synthesis and biological activities of endo-3,6-epoxy-1,2,3,6-tetrahydrophthalimide and its polymers

Photocopolymerizations of endo-3,6-epoxy-1,2,3,6-tetrahydrophthalimide (ETPI) with acrylic acid (AA), vinyl acetate (VAc), and maleic anhydride (MAH) were carried out in a mixed solvent of 2-butanone and acetone using 2,2-dimethoxy-2-phenylacetophenone as an initiator at 25°C. Synthesized ETPI, poly(ETPI), poly(ETPI-co-AA), poly(ETPI-co-VAc), and poly(ETPI-co-MAH) were characterized by IR and ¹H-NMR spectroscopies, elemental analysis, and gel permeation chromatography. The synthesized polymers have a number-average molecular weight (M_n) in the range of 3500-27,400. The in vitro cytotoxicities of poly(ETPI), poly(ETPI-co-AA), poly(ETPI-co-VAc), and poly(ETPI-co-MAH) against fibroblast and K-562 human leukemia cells were lower than that of monomeric ETPI at a low concentration (0.02 mg/mL). The in vivo antitumor activities of the polymers were evaluated by the survival time with sarcoma 180 tumor-bearing mice. The polymers showed higher antitumor activity and lower toxicity than both monomeric ETPI and 5-fluorouracil at all doses tested. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 64: 2605–2612, 1997     

A study on the laser curing of acrylic resin for the application in screen printing

For the development of an economic, automated, and computer-aided manufacturing process of screen for textile printing, photocuring of acrylic resin by an argon ion laser was studied. A commercially available polyurethane–acrylate resin was selected as a test resin for the representative study on laser curing behavior. The photoreaction by laser was observed by infrared spectroscopic analysis of vinyl group. With 1-W input power, the degree of curing increased linearly with exposure time, which reached, however, a plateau with exposure time of more than 4 μs. The curing reaction could be characterized in an S-shaped curve due to the combined effect of oxygen inhibition at lower power and photon saturation at higher power. The viscosity of acrylic resin could be controlled by addition of water as diluent without any significant drawback in curing speed. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 73: 515–520, 1999     

Synthesis and characterization of novel aromatic-aliphatic poly(amide-imide-imide)s (PAII)

Novel poly(amide-imide-imide)s (PAII) were prepared by polycondensation of a new monomer synthesized from trimellitic anhydride and glutamic acid, followed by reflux condensing with thionyl chloride and several diamines. Polymers and monomers were characterized by ¹H NMR and FT-IR spectroscopy, elemental analysis and mass spectrometry. Inherent viscosities of the resulting polymers were in the range of 17–26 mL g^–1 (M_w 13 400–29 160, polydispersity (M_w/M_n) ca. 1.3–1.7), representing rather low molecular weights. The glass transition temperatures of the polymers were in the range of 210–285°C depending on the structure of diamines, and the thermal stability of the polymers was up to 400°C, comparable with that of polyimides and poly(amide imide)s. All the polymers synthesized are well soluble in aprotic polar solvents such as dimethylformamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone and dimethylacetamide. Particularly, polymers containing oxydianiline and 4,4′-diaminodiphenyl sulfone were quite soluble in m-cresol, pyridine, nitrobenzene and tetrahydrofuran.     

Survey on blockchain-based non-fungible tokens: History,technologies, standards,and open challenges

This paper presents a survey of non-fungible tokens (NFTs), including its history, technologies, standards, and challenges in their development. An NFT is a unique digital entity that is created and maintained using blockchain technology. Each NFT is identified using a unique smart contract and a token ID, so the whole history of the NFT can be globally identified by its address and token ID. The blockchain information indelibly identifies the current owner of any asset, previous owners, and original creator. NFTs are used to manage ownership of digital and physical assets and cryptocurrencies. The prices of popular NFTs have become very high, and the market for them has overheated in recent years. NFT technology and its ecosystem have evolved since Quantum, the first NFT, was stored in the Namecoin blockchain. Ethereum has become the main platform for NFT projects because it provides support for smart contracts. Currently, almost all NFT projects are launched on the Ethereum blockchain. NFT has two major standards called ERC-721 and ERC-1155, which have had important functions in the development of NFT. Starting with these two standards, other standards for NFT continue to emerge; they expand the functionality of NFT such as by adding utility. However, NFT is a very early technology, and it has not been long after the NFT concept was created and used. So there are several challenges for further improving NFT technology, in terms of usability, interoperability, and evolution. This paper presents a survey of NFT, including its history, technologies, standards, and challenges of NFT.     

Effects of different types of salts on the growth of lactic acid bacteria and yeasts during kimchi fermentation

Food Science and Biotechnology - Kimchi was prepared with different types of salts: purified salt (PS), solar salt aged for 1 year (SS1), aged for 3 years (SS3), and bamboo salt...