Cationic Polymers for Coating Living Cells

홍대화,양성호 한국고분자학회 2018 Macromolecular Research Vol.26 No.13

Cytocompatible coating of living cells have been reported as useful methods for enhancing stability of inner cells under in vitro conditions, providing chemical functionality on cell surfaces, and controlling kinetics of cell proliferations. These chemically driven events are often utilized for the development of cell based sensor, tissue engineering, and cell therapy, as well as for understanding single-cell behavior. Because most of the cell surface is negatively charged, selection and control of cationic polymers are significant for enhancing electrostatic interactions between the cell surface and the polymer, and for reducing toxicity of the cationic polymers. In this review, cationic polymers used for coating living cells are highlighted as a single layered coat, as a component of layer-by-layer (LbL) film with anionic polymer species, or as a catalytic template inducing inorganic materials of interest. Cationic biopolymers and synthetic polymers compatible to the target cell are covered in this review.

A self-assembled polymeric micellar immunomodulator for cancer treatment based on cationic amphiphilic polymers

Yim, H.,Park, W.,Kim, D.,Fahmy, T.M.,Na, K. IPC Science and Technology Press 2014 Biomaterials Vol.35 No.37

Here, we report a self-assembled polymeric micellar immunomodulator (SPI) for enhanced cancer treatment based on cationic amphiphilic polymers. To obtain the cationic amphiphilic polymer, the hydrophobic all-trans-retinoic acid (ATRA) was conjugated with a hydrophilic low-molecular-weight PEI (<SUB>Low</SUB>PEI, M<SUB>n</SUB> = 1.8 kDa). The ATRA-<SUB>Low</SUB>PEI conjugates could self-assemble in aqueous media, forming micelles with a strong positive charge (~+40 mV) and particle sizes of ~70 nm. Compared to conventional therapeutic agents (e.g., cisplatin), the SPI exhibited enhanced anti-cancer activity regardless of drug resistance. After mechanistic in vitro cell death studies, we revealed that the mechanical disruptive force generated by the cationic charge of SPI primarily induced necrotic cell death. Furthermore, the organelle fragments induced by the necrotic cell death triggered antitumoral immune responses. Therefore, SPI induced synergistic effects of the cationic charge-induced necrosis and antitumoral immune responses could produce an effective cancer treatment. In addition, the SPI was shielded by hyaluronic acid (HA/SPI complex) to enhance its tumor selectivity in vivo. Finally, the HA/SPI complex accumulated selectively into tumor sites after systemic administration into tumor-bearing mice, exhibiting effective antitumoral effects without systemic toxicity. Therefore, this technology holds great potential for translation into a clinical cancer treatment.

A Weakly Cationic Temperature Tolerant and Salt Resistant Polymer: Synthesis and Properties

Bo Deng,Xueqin Luo,Feng Jiang,Wei Liu,Jianwei Gu,Chao Liu,Yanan Song 한국고분자학회 2022 Macromolecular Research Vol.30 No.8

In the petroleum industry, water-soluble polymers can be used as oil displacement agents. However, the use of water-soluble polymers is limited because of poor temperature and salt resistance. To improve temperature and salt resistance, a weakly cationic polymer with large side groups (PAM/AMPS/VI) was prepared by copolymerizing acrylamide (AM) with 2-acrylamido-2-methylpropane sulfonic acid (AMPS) and 1-vinylimidazole (VI). The viscosity of PAM/AMPS/VI water solutions can be increased more than 20 mPa·s compared with PAM/AMPS. In addition, the viscosity of the solution increased continuously after aging at 80℃, showing good temperature and salt stability. The protonated tertiary amine in the imidazole ring electrostatically interacts with the sulfonic group, increasing the viscosity and salt resistance of the polymer. The five-membered ring of imidazole also enhances the rigidity of the polymer chain and improves the temperature tolerance. As a confirm of the result, a complete spatial network of PAM/ AMPS/VI was observed in scanning electron microscopy (SEM) micrographs. Using weak cationic polymers with large side groups can provide a reference for the design of new temperature tolerance and salt resistant polymer.

FRET 기반 고분자 센서의 DNA 검출 감도 향상을 위한 연구

김보람 ( Bo Ram Kim ),우한영 ( Han Young Woo ) 한국화상학회 2010 한국화상학회지 Vol.16 No.3

Signal amplification in fluorescence resonance energy transfer (FRET)-based DNA detection was investigated by using cationic polyfluorene as a FRET donor and fluorescein (Fl)-labeled single stranded DNA (ssDNA-Fl) as a FRET acceptor for improving detection sensitivity. The FRET rate is very sensitive to the intermolecular distance and the FRET efficiency increases with decreasing distance between FRET donor (D) and acceptor (A). However, the energy wasting photo-induced charge transfer (PCT) quenching also increases with decreasing D-A intermolecular distance. The competition between the FRET and PCT processes can be controlled by modifying D-A intermolecular distance. The Layer-by-Layer (LbL) assembling technique is expected to provide a fine-control of the FRET D-A intermolecular distance. By LbL assemblies, we controlled the number of inter layers between cationic polyfluorene and ssDNA-Fl, and the resulting FRET-induced signal was successfully modulated by changing the intermolecular D-A distance on the molecular level. Therefore, the LbL technique can suggest an efficient way to fine-tune the competition between FRET and PCT for maximizing detection sensitivity in FRET-based DNA biosensors.

Cationic Polymer Development for mRNA Delivery and their Application for CRISPR-Cas Technology

HyunJin KIM 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.4

Efficient nonviral vector gradually become an essential requisite for successful gene editing therapy via CRISPR-Cas technology, which Cas9 protein edits guide RNA (gRNA)-complementary target chromosome DNA. The nonviral vector in the local administration can accomplish gene editing in the area of interest without inducing undesirable gene editing in the off-region. We have developed amphiphilic polyaspartamide derivatives (PAsp(DET/CHE)) to induce transient and high Cas9 protein expression from messenger RNA (mRNA). Diethylenetriamine (DET) moiety provides high endosomal escape ability and associates with negatively charged mRNA. 2-Cyclohexylethyl (CHE) moiety optimizes polymer hydrophobicity between mRNA nanoparticle stability in the extracellular condition and mRNA release in the cytoplasm. CHE moiety was selected from the highest luciferase mRNA expression in cultured cells among ~20 aliphatic groups between 5 and 10 carbon atoms. PAsp(DET/CHE) was synthesized via two-step process. The precursor polymer poly(β-benzyl-L-aspartate) (PBLA) were synthesized with ring opening polymerization between n-butylamine and β-benzyl-L-aspartate N-carboxy-anhydride (BLA-NCA) to have degree of polymerization (DP) of 26. PAsp(DET/CHE) was synthesized by co-aminolysis of DET and CHE into PBLA to contain 15 DET and 11 CHE moieties. Interestingly, the mRNA translation efficacy was not affected by DP of PAsp(DET/CHE) from 26 to 121 but by the amounts of CHE moieties in the single polymer. The PAsp(DET/CHE) with less than 8 CHE introduction amounts did not increase mRNA translation efficacy at all but dramatically enhanced the translation efficacy with more than 11 CHE introduction amounts. We analyzed in vitro cellular uptakes, endosomal escape ability, and release kinetics of mRNA in cytoplasm to clarify the mechanism of high mRNA translation of PAsp(DET/CHE). Gene editing was evaluated in Ai9 mouse, which red fluorescence occurs in the results of Cas9/gRNA based STOP cassette cleavages. The nano-particles were prepared with mixing between PAsp(DET/CHE) and Cas9 mRNA (or gRNA). The nanoparticles (1.5 ug Cas9 mRNA and 1.5 ug sgRNA) were locally injected into ventricular area of the Ai9 mouse. At 2day post-administration, the brain was dissected and observed by using confocal laser scanning microscope (CLSM). Gene editing occurred in the ependymal layer and choroid plexus of almost all brain area, which indicated high delivery efficiency of PAsp(DET/CHE) into the brain. PAsp(DET/CHE) has high gene editing efficacy in the local delivery into brain, nose, and muscle. These indicate high potential of the hydrophobicity optimization of polyaspartamide derivatives and demonstrates the strong potential of PAsp(DET/CHE) for in vitro and in vivo Cas9 mRNA/gRNA delivery.

Fabrication of Pre-Exfoliated Clay Masterbatch via Exfoliation-Adsorption of Polystyrene Nanobeads

Khvan, Svetlana,Kim, Jun-Kyung,Lee, Sang-Soo The Polymer Society of Korea 2007 Macromolecular Research Vol.15 No.1

The approach studied in the present work produced an exfoliated state of clay layers via confinement of the charged nano-sized polystyrene (PS) beads within the gallery of swollen pristine clay. It was demonstrated that adsorption of the polymer nanobeads dramatically promotes expansion of the clay gallery. A comparative study of incorporation was conducted by employing organo-modified clay along with two different colloid polymer systems: electrostatically stabilized PS nanobeads and cationic monomer-grafted PS nanobeads. The mechanism of adsorption of the monomer-grafted polymer beads onto clay via cationic exchange between the alkyl ammonium group of the polymer nanobeads and the interlayer sodium cation of the layered silicate was verified by using several techniques. As distinct from the polymer nanobeads formed using conventional miniemulsion polymerization method, competitive adsorption of stabilizing surfactant molecules was be prevented by grafting the surface functional groups into the polymer chain, thereby supporting the observed effective adsorption of the polymer beads. The presence of surface functional groups that support the establishment of strong polymer-clay interactions was suggested to improve the compatibility of the clay with the polymer matrix and eventually play a crucial role in the performance of the final nanocomposites.

Tunable biocompatible immune accelerator in vaccination

이지민,신희준,나건 한국공업화학회 2020 한국공업화학회 연구논문 초록집 Vol.2020 No.-

Surgery, chemotherapy, and radiation therapy are commonly used for treatment of solid tumor. However, it is hard to remove primary tumor thoroughly, and chemo-drug can be toxic to even normal cells. Moreover, solid tumor has immunosuppressive tumor microenvironment (TME), which restrain T cell activity, and it leads to relapse of tumors. In accordance with these limitations, we developed anticancer immunotherapeutic agent using cationic polymer as an immune accelerator. A new platform was composed of acidic cleavable linker and cationic polymer. We confirmed charge conversion property of this platform at TME. Also, we showed biocompatibility by protecting cationic residues with linkers. In vivo test proved that the platform is good at not only targeting tumor cells because of its strong interaction with tumor cellular membranes in TME, but also evoking necrosis and apoptosis which bring about immune response.

Fabrication of core-shell particles for a fluidized bed electrode in seawater desalination

Kim, E.H.,Jung, Y.G.,Lee, J.H.,Yeo, J.G.,Yang, S.C.,Choi, J. Elsevier Sequoia 2014 Surface & Coatings Technology Vol.260 No.-

Active carbon particles have been coated with cation-exchanged polymer for the fabrication of core-shell particles, to be used as a fluidized bed electrode in seawater desalination. To adequately utilize the features of the core-shell particles, the polymer should be uniformly coated on the surface of independent active carbon particles. To do that, the active carbon particles prior to the polymer coating were modified with an acid for individual separation without agglomeration between particles, producing a more effective coating of polymer on the carbon particles. The modified carbon particles were well dispersed in an aqueous solution with cation-exchanged polymer by the hydrophilic groups generated on the carbon chain, resulting in the homogeneous coating of polymer on the surface of individual carbon particles. This means that the core-shell particles prepared with heterogeneous materials could be applicable to a fluidized bed electrode in seawater desalination.

Gene Delivery by PAMAM Dendrimer Conjugated with the Nuclear Localization Signal Peptide Derived from Influenza B Virus Nucleoprotein

이제일,이슬기,권용은,김윤중,최준식 한국고분자학회 2019 Macromolecular Research Vol.27 No.4

Polyamidoamine (PAMAM) dendrimer is one of the cationic polymers widely used in nonviral vector-based gene therapy. As PAMAM comprises biodegradable peptide bonds, it shows biocompatibility and relatively low cytotoxicity. In comparison with polyethylenimine (PEI, 25 kDa) that shows high transfection efficiency, the native PAMAM dendrimer has limitations as a gene carrier. To improve the gene expression efficiency, we introduced KRTR peptides derived from the influenza B virus nucleoprotein, known as a nuclear localization signal (NLS), to PAMAM generation 3. We synthesized PAMAM-RTRK and PAMAM-HRTRK and evaluated the effects of the histidine residue on cytotoxicity. The transfection efficiency of PAMAM-RTRK and PAMAM-HRTRK was similar to that of PEI in HepG2 cells, while their gene expression capacities were much higher than capacity of PEI in A549 cells. PAMAM-HRTRK showed relatively lower cytotoxicity than PAMAM-RTRK in the two cell lines, but the transfection capacity was similar for the two polymers. These results imply that the combination of histidine and KRTR peptide may potentially result in a novel PAMAM-based vector that could be used for prolonged gene therapy through the reduction in cytotoxicity and enhancement of gene expression.

Analytical and environmental applications of polyaniline Sn(IV)tungstoarsenate and polypyrrole polyantimonic acid composite cation-exchangers

Mohammad Mezbaul Alam,Zeid A. AlOthman,Mu. Naushad 한국공업화학회 2013 Journal of Industrial and Engineering Chemistry Vol.19 No.6

Two organic–inorganic type composite materials were prepared via the incorporation of organic conducting polymers into the inorganic precipitates of multivalent metal acid salts to explore their analytical and environmental applications. Vital uses of these materials for the analyses of water pollution were demonstrated by the quantitative separation of Cd2+ and Hg2+ from some synthetic and real samples onto their columns. Separation and determination of Zn2+ and Fe2+ in the pharmaceutical preparations were also performed. The adsorption behavior of dichlorvos (insecticide) on the surface of polyaniline Sn(IV) tungstoarsenate was studied which indicating its usefulness in the decrease of environmental pollution load.