Polyion Complex Research Articles

Liver drug damage: possibilities of polyionic succinate-methioninic complex during the pandemic of new coronavirus infection (COVID-19)

Medicinal liver damage is an important problem not only in the framework of hepatology and gastroenterology, but also for internal medicine in general, which is due to the difficulties of correct and timely diagnosis of this pathology. In the first part of the review, the main mechanisms of liver tissue damage and clinical and formological manifestations of drug-induced liver damage are considered.The pandemic of the new coronavirus infection (COVID-19), spread by the SARS-CoV-2 virus, has become a challenge to health systems around the world. The global clinical experience gained over the past year in the management of patients with a new coronavirus infection makes it possible to highlight a number of relevant clinical aspects, one of which is drug-induced liver damage associated with the treatment of COVID-19. In the second part of the review, the possible mechanisms of influence of COVID-19 on the hepatobiliary system are considered, which include viral cytotoxicity, a secondary effect of immune dysregulation; hypoxia as a result of respiratory failure and subsequent ischemic liver damage; reactivation of already existing liver pathology and drug damage to the liver. It has been established that a large number of drugs used to treat COVID-19 - antiviral agents, antibacterials, non-steroidal anti-inflammatory drugs, steroids and others - have hepatoxic effects and can cause liver damage. In the context of the COVID-19 pandemic, for patients with a new coronavirus infection and drug-induced liver damage, a rational, pathogenetically justified choice of a hepatoprotective drug is of particular importance. In the final part of the review, the possibilities of the polyionic succinate-methionine complex in the treatment of drug-induced liver damage are considered and a clinical example of the drug application in a patient with drug-induced liver damage during treatment with COVID-19 is given.

Bioinspired Silicification of mRNA-Loaded Polyion Complexes for Macrophage-Targeted mRNA Delivery.

In vitro transcribed messenger RNA (mRNA) delivery to macrophages is a promising therapeutic modality for inflammatory diseases because it can modulate the immunological activity of macrophages. However, efficient macrophage-targeted mRNA delivery remains challenging. Herein, we fabricated silica-coated polyion complexes (PICs), termed SilPICs, via bioinspired silicification for stable encapsulation of mRNA and scavenger receptor (SR)-mediated macrophage targeting. Silica coating was readily performed by simply mixing mRNA-loaded PICs with tetramethyl orthosilicate in aqueous media at 25 °C. The silica shell formation was verified by a slight increase in size (∼18 nm), a conversion of ζ-potential from positive (+22 mV) to negative (-23 mV), the peak appearance derived from silanol groups and siloxane bonds in the IR spectra, and elemental analyses by scanning transmission electron microscopy-energy-dispersive X-ray spectrometry (STEM-EDS). The silica shell efficiently protected the mRNA payload from enzymatic degradation in a fetal bovine serum-containing medium. Meanwhile, the reversibility of the silica shell allowed mRNA release from SilPICs after silica dissolution into silicic acids under diluted conditions. Furthermore, SilPICs elicited 20-fold higher mRNA transfection efficiency in the macrophage cell line RAW264.7 compared to noncoated PICs, presumably due to the facilitated cellular internalization by the silica shell. These enhancements were compromised in the RAW264.7 cells incubated with dextran sulfate and poly(inosinic acid) as inhibitors of SR type A1 and were not observed in cultured CT26 colon cancer cells, which are SR-negative cells. Collectively, SilPIC is a promising mRNA delivery vehicle with both mRNA protectability and macrophage targetability.

The Core–Shell Structure, Not Sugar, Drives the Thermal Stabilization of Single-Enzyme Nanoparticles

Trehalose is widely assumed to be the most effective sugar for protein stabilization, but exactly how unique the structure is and the mechanism by which it works are still debated. Herein, we use a polyion complex micelle approach to control the position of trehalose relative to the surface of glucose oxidase within cross-linked and non-cross-linked single-enzyme nanoparticles (SENs). The distribution and density of trehalose molecules in the shell can be tuned by changing the structure of the underlying polymer, poly(N-[3-(dimethylamino)propyl] acrylamide (PDMAPA). SENs in which the trehalose is replaced with sucrose and acrylamide are prepared as well for comparison. Isothermal titration calorimetry, dynamic light scattering, and asymmetric flow field-flow fraction in combination with multiangle light scattering reveal that two to six polymers bind to the enzyme. Binding either trehalose or sucrose close to the enzyme surface has very little effect on the thermal stability of the enzyme. By contrast, encapsulation of the enzyme within a cross-linked polymer shell significantly enhances its thermal stability and increases the unfolding temperature from 70.3 °C to 84.8 °C. Further improvements (up to 92.8 °C) can be seen when trehalose is built into this shell. Our data indicate that the structural confinement of the enzyme is a far more important driver in its thermal stability than the location of any sugar.

Effects of Organic Acids on Drug Release From Ternary Polypeptide Nanoparticles Entrapping Carfilzomib

Carfilzomib (CFZ) is an FDA-approved proteasome inhibitor with antineoplastic properties against various cancers, yet its short blood retention time after intravenous injection (< 30 min) makes clinical applications limited to multiple myeloma. We previously developed ternary polypeptide nanoparticles (tPNPs) as a new nanoparticle formulation of CFZ to overcome these limitations. The formulation was prepared by polyion complexation between poly(ethylene glycol)-poly(L-glutamate) block copolymers (PEG-PLE) and CFZ-cyclodextrin (CD) inclusion complexes, where CDs were positively charged with 7 primary amines attached while PEG-PLE carried 100 carboxyl groups per polymer chain. Although tPNPs greatly improved biostability of CFZ, CFZ-loaded tPNPs (CFZ-tPNPs) still showed burst drug release and mediocre drug retention under physiological conditions. To address these issues, organic acids are tested as stabilizers in this study to improve particle stability and drug retention for tPNPs. Charge densities in the core of CFZ-tPNPs were optimized with selected organic acids such as citric acid (CA) and lactic acid (LA) at varying mixing ratios. Organic acids successfully maintained small particle size suitable for intravenous injection and drug delivery (diameters < 60 nm), improved CFZ solubility (> 1 mg/mL), allowed for lyophilization and easy reconstitution in various buffers, enhanced drug retention (> 60% post 24 h incubation), and suppressed burst drug release in the first 6 h following solubilization. These results demonstrate that organic acid stabilized tPNPs are useful as an injection formulation of CFZ, which may expand the utility of the proteasome inhibitor.

Encapsulation of a cationic antimicrobial peptide into self-assembled polyion complex nano-objects enhances its antitumor properties

Antimicrobial peptides, a large class of molecules synthetized by various organisms as an innate defense against pathogens are more and more used for their anticancer properties as well. In order to overcome some of their limitations and to enhance their therapeutic efficiency, the use of delivery systems was taken into consideration. In this study we describe an original delivery system for antimicrobial peptides based on its physico-chemical properties, namely the self-assembled polyion complexes (PIC) based on electrostatic interactions of cationic antimicrobial peptide P6 with negatively charged double hydrophilic block copolymers, the poly(ethylene oxide)-poly(acrylic acid) (PEO-PAA) in our study. The drug delivery system was tested on 3D human tumor HCT-116 spheroids. The spheroid evolution and cell viability were monitored at 24 and 48 h after the treatment was applied. Our study demonstrates for the first time the feasibility of forming a polyion complex PIC with an antimicrobial peptide and that this self-assembled organization provides added value in terms of anti-tumor therapeutic efficacy compared to the free form of the antimicrobial peptide.

Block catiomer with flexible cationic segment enhances complexation with siRNA and the delivery performance in vitro

RNA interference (RNAi) by small interfering RNAs (siRNAs) is a promising therapeutic approach. Because siRNA has limited intracellular access and is rapidly cleared in vivo, the success of RNAi depends on efficient delivery technologies. Particularly, polyion complexation between block catiomers and siRNA is a versatile approach for constructing effective carriers, such as unit polyion complexes (uPIC), core-shell polyion complex (PIC) micelles and vesicular siRNAsomes, by engineering the structure of block catiomers. In this regard, the flexibility of block catiomers could be an important parameter in the formation of PIC nanostructures with siRNA, though its effect remains unknown. Here, we studied the influence of block catiomer flexibility on the assembly of PIC structures with siRNA using a complementary polymeric system, i.e., poly(ethylene glycol)-poly(L-lysine) (PEG-PLL) and PEG-poly(glycidylbutylamine) (PEG-PGBA), which has a relatively more flexible polycation segment than PEG-PLL. Mixing PEG-PGBA with siRNA at molar ratios of primary amines in polymer to phosphates in the siRNA (N/P ratios) higher than 1.5 promoted the multimolecular association of uPICs, whereas PEG-PLL formed uPIC at all N/P ratios higher than 1. The PEG-PGBA multimolecular PICs did not dissociate upon dilution in HEPES buffer, though they disassembled into uPICs in physiological salt concentration. Moreover, uPICs from PEG-PGBA were more stable against counter polyanion exchange than uPICs from PEG-PLL, probably due to a favorable complexation process, as suggested by computational studies of siRNA/block catiomer binding. In in vitro experiments, PEG-PGBA uPICs promoted effective intracellular delivery of siRNA and efficient gene knockdown. Our results indicate the significance of polycation flexibility on assembling PIC structures with siRNA, and its potential for developing innovative delivery systems.

Hierarchical polyion complex vesicles from PAMAM dendrimers

Hierarchical dendrimer-based polyion complex (PIC) vesicles with multiple compartments have attracted considerable attention as functional delivery vehicles and nano-carriers. Formation of these vesicles relies on the electrostatic assembly of asymmetric polyelectrolytes, namely branched dendrimers with linear polyion-neutral diblock copolymers. However, successful incorporation of dendrimers in vesicle lamellae is challenging due to the compact structure of dendrimers, and therefore, vesicles reported so far are prepared mainly with low generation dendrimers which lack the cavity required for carrier functions. Here, we present a new assembly combination of amine-terminated dendrimer polyamidoamine (PAMAM) with polyion-neutral diblock copolymer poly (styrene sulphonate-b-ethylene oxide) (PSS-b-PEO). The strong charge interaction between the building blocks leads to stable and well-defined PIC vesicles that can tolerate not only different PSS block lengths but, more importantly, also different dendrimer generations from 2 to 7. As a consequence, high generation dendrimers with a cavity can be packed in the vesicle wall, and one obtains hierarchical PIC vesicles with multiple compartments, namely the dendrimer cavity for loading small hydrophobic cargo, and the vesicle lumen for encapsulating hydrophilic macromolecules. Our study demonstrates that combining proper building blocks enables to manipulate the charge interactions, which is essential for controlling the dendrimer packing and the formation of PIC vesicles. These findings should be helpful for understanding the assembly of asymmetric (linear / branched) polyelectrolyte complexes, as well as for designing new hierarchical PIC vesicles for controlled delivery of multiple active substances.

Lignosulfonate/diblock copolymer polyion complexes with aggregation-enhanced and pH-switchable fluorescence for information storage and encryption

Employing natural polymers as building blocks is favorable to construct sustainable functional materials and realize biomass utilization. Here we developed a series of supramolecular polyion complexes (PICs) composed of lignosulfonate and double-hydrophilic diblock copolymer poly(ethylene oxide-b-N, N-dimethylaminoethyl methacrylate) (PEO114-b-PDMAEMA24), which performed a blue emission with quenching-enhancing tendency and copolymer distribution inversion-involved assembling transformation at pH 5.6 and monotonic greenish-blue fluorescence promotion at pH 9.5 by increasing PEO114-b-PDMAEMA24 contents. Electrostatic interactions and multiple hydrogen bonds were revealed controlled the assembling behavior and affected the emission via altering the restriction of molecular motion, through-space conjunction, and non-luminous complexation. The multiple interacting sites and special topology of diblock copolymer contributed to the efficient fluorescence regulation. Information writing-erasing and encryption-decryption systems were established by utilizing emission intensity regulation and pH-responsive emission chromism. This work paved a new way to enhance lignin fluorescence and broadened potential applications of lignin composites in realms of sensing, imaging, monitoring, and anticounterfeiting.

All-Peptide-Based Polyion Complex Vesicles: Facile Preparation and Encapsulation of the Protein in Active Form.

The polyion complex vesicle (PICsome) is a promising platform for bioactive molecule delivery as well as nanoreactor systems. In addition to anionic and cationic charged blocks, a hydrophilic poly(ethylene glycol) (PEG) block is mostly employed for PICsome formation; however, the long-term safety of the PEG component in vivo is yet to be clarified. In this study, we developed novel PEG-free PICsome comprising all peptide components. Instead of the PEG block, we selected the sarcosine (Sar) oligomer as a hydrophilic block and fused it with anionic oligo(l-glutamic acid). Mixing the Sar-containing anionic peptide with cationic oligo(l-lysine) resulted in the formation of stable vesicles. The peptide-based PICsome was able to encapsulate a model protein in its hollow structure. After modification of the surface with a cell-penetrating peptide, the protein-encapsulated PICsome was successfully delivered into plant cells, indicating its promised for application as a biocompatible carrier for protein delivery.

Nanoscale Polyion Complex Vesicles for Delivery of Cargo Proteins and Cas9 Ribonucleoprotein Complexes to Plant Cells

DNA-free genome editing using Cas9 ribonucleoprotein is advantageous because it introduces fewer potential undesirable genetic modifications than comparable methods. Here, we show a direct protein delivery system for plants using a cell-penetrating peptide-displayed polyion complex vesicle, CPP-PICsome, as a biological nanocarrier. With this system, we demonstrate nuclear genome editing by delivery of a Cas9 ribonucleoprotein complex in Arabidopsis thaliana callus.

Development of a label-free ATP image sensor for analyzing spatiotemporal patterns of ATP release from biological tissues

Abstract We investigated the output characteristics of a label-free, 37.3 μm pitch, 128 × 128 pixel adenosine-5'-triphosphate (ATP) image sensor, in which different thicknesses of ATP-degrading enzyme apyrase were deposited using the poly-ion complex (PIC) method. ATP was detected based on the changes in the concentration of hydrogen ions (H+) generated by enzymatic reactions. Enzyme films of different thicknesses were formed on the surface of the sensor by controlling the volumes of the PIC solution. A reduction in the enzyme film thickness (0.2 μm thickness), improved the sensitivity of the ATP sensor, and a clear image than that obtained with a sensor with a thicker film (2.3 μm thickness) was obtained. Additionally, the detection limit for the 0.2-μm-thick sensor was as low as 10 μM, whereas that of the 2.3-μm thick sensor was 100 μM. To examine ATP release from biological tissues, we placed a mouse hippocampal slice on the sensor with the 0.2-μm-thick film and electrically stimulated the nerve fiber (i.e., the Schaffer collateral). The neuronal stimulation evoked significant changes in the output signals of the hippocampal slice but not in the sensor area which was not in contact with tissue. An elevation in the output signal was initiated at the stimulated site with a maximum increment of 5 mV, and the signal traveled along the neuronal fibers. By reducing the film thickness, we successfully developed a high-sensitivity label-free ATPo image sensor with a high spatiotemporal resolution, which allows imaging of endogenous ATPo released from the hippocampus.

Challenges to Creation of Artificial Organelle for Effective Editing of Cell Function

In "cell-function editing", the combination of biological methods with artificial methods is a promising way to effectively implement functions that live cells do not originally possess. In the present symposium review, two approaches with methodology of building "artificial organelle" were implemented for editing cellular functions. One approach is the "membrane-bound artificial organelle", which is mainly created from polymeric nanocapsules that function in cells, and the other approach mimics the "membraneless organelle", which has recently gained immense interest in the field of cell biology. Furthermore, some examples of artificial cells are also described, which were constructed by utilizing artificial organelles. In this context, some recent progress has been observed in the author's research on the development of polyion complex (PIC) materials, in particular, PICsome-based nanoreactors, designer coacervates for protein sequestration, and yolk-shell PIC structures that are reminiscent of artificial cells. These technologies may contribute to effective "cell editing" or "cell renovation", which enables the edited cells to show higher performance at the target site in the human body, compared to the native cells.

Hybrid Polymeric Nanostructures Stabilized by Zirconium and Gadolinium Ions for Use as Magnetic Resonance Imaging Contrast Agents

Nanostructures called hybrid polyion complexes (HPICs) are formed by adding metal ions to a solution of a double-hydrophilic block copolymer, leading to the spontaneous formation of highly monodisp...

Growth factor functionalized biodegradable nanocellulose scaffolds for potential wound healing application

Nanocellulose has been highlighted as one of the most promising biomaterials for biomedical applications with the potential to outperform conventional polymeric materials. However, the design of nanocellulose-based biomaterials for wound healing still requires precise control over biophysical and biochemical cues to direct a series of cellular activities in healing processes. The bioactive cellulose nanofibrils scaffolds with controlled release of basic fibroblast growth factors (bFGFs) were constructed for potential wound healing applications. The Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) analysis revealed the polyion complex interaction between the positively charged bFGFs with the negatively charged cellulose nanofibrils, which mimics the interaction between bFGFs and heparin sulfate in extracellular matrix in the body. Such association enables not only the storage of bFGFs in a readily available form and from where it is slowly released, but also potential protection of it from denaturation. The release profile of bFGFs from the CNF scaffolds was tailored by tuning the CNF surface chemistry and in situ deconstruction of the scaffolds. The in situ enzymatic deconstruction of the scaffolds provides a possibility to tune the bioavailability of bFGFs for cell growth and proliferation, and more importantly, to balance the scaffolds degradation and new tissue formation in wound healing. The MTT assay of cells proliferation and fluorescence imaging of cells cultured in the 3D scaffolds showed that the CNF scaffolds loaded with bFGF can significantly facilitate the proliferation of the cells, even if only a small amount of bFGF was loaded. Enzymatic deconstruction of the CNFs network further increases the bFGFs bioavailability, and promotes cell proliferation. This work may serve as an important step toward the development of nanocellulose-based biomaterials with tailored biophysical and biochemical cues for wound healing and other biomedical applications.

Treatment of primary and metastatic breast and pancreatic tumors upon intravenous delivery of a PRDM14-specific chimeric siRNA/nanocarrier complex.

PRDM14 is highly expressed in several cancers but is not detected in normal tissues. It confers cancer stem cell-like properties, including chemoresistance and distant metastasis, to cancer cells. Herein, we aimed to develop a highly effective therapy against advanced stage cancer based on intravenously delivered PRDM14-targeted siRNA. First, we examined PRDM14 expression and gene amplification in breast and pancreatic tumors and cell lines. PRDM14 was expressed in breast cancer, including the triple-negative subtype, and pancreatic cancer. PRDM14 was amplified in 23.8% of patients with PRDM14+ breast cancer. Next, we investigated the inoculated tumor growth and distant metastasis following PRDM14 depletion by administering mice with PRDM14-specific chimeric siRNA combined with a novel branched PEGylated poly-L-ornithine (PLO)-based intravenous drug delivery system, designated PRDM14 unit polyion complex (uPIC) (n = 6/group). Inhibition of PRDM14 expression with PRDM14 uPIC by systemic intravenous injection effectively reduced tumor size and metastasis in vivo, thereby improving survival. Finally, pharmacokinetic/toxicokinetic analyses were performed on PRDM14 uPIC, which was intravenously administered to rats (n = 10-15/group) and cynomolgus monkeys (n = 3-5/group), twice weekly for 4 weeks. This revealed that PRDM14 uPIC was relatively nontoxic and the siRNA exposure in serum was greater than that predicted by the administered dose ratio when delivered as a uPIC. Taken together, our study indicated that PRDM14 uPIC is highly effective in suppressing malignant features of solid cancers and does not cause severe toxicity, making it a promising therapeutic agent for cancer treatment.

Superoxide Dismutase 1 Nanoparticles (Nano-SOD1) as a Potential Drug for the Treatment of Inflammatory Eye Diseases.

Inflammatory eye diseases remain the most common clinical problem in ophthalmology. The secondary processes associated with inflammation, such as overproduction of reactive oxygen species (ROS) and exhaustion of the endogenous antioxidant system, frequently lead to tissue degeneration, vision blurring, and even blindness. Antioxidant enzymes, such as copper–zinc superoxide dismutase (SOD1), could serve as potent scavengers of ROS. However, their delivery into the eye compartments represents a major challenge due to the limited ocular penetration. This work presents a new therapeutic modality specifically formulated for the eye on the basis of multilayer polyion complex nanoparticles of SOD1 (Nano-SOD1), which is characterized by appropriate storage stability and pronounced therapeutic effect without side reactions such as eye irritation; acute, chronic, and reproductive toxicity; allergenicity; immunogenicity; mutagenicity even at high doses. The ability of Nano-SOD1 to reduce inflammatory processes in the eye was examined in vivo in rabbits with a model immunogenic uveitis—the inflammation of the inner vascular tract of the eye. It was shown during preclinical studies that topical instillations of Nano-SOD1 were much more effective compared to the free enzyme in decreasing uveitis manifestations. In particular, we noted statistically significant differences in such inflammatory signs in the eye as corneal and conjunctival edema, iris hyperemia, and fibrin clots. Moreover, Nano-SOD1 penetrates into interior eye structures more effectively than SOD itself and retains enzyme activity in the eye for a much longer period of time, decreasing inflammation and restoring antioxidant activity in the eye. Thus, the presented Nano-SOD1 can be considered as a potentially useful therapeutic agent for the treatment of ocular inflammatory disorders.

Hybrid polyion complex micelles enabling high-performance lithium-metal batteries with universal carbonates

Lithium (Li) metal emerges as an anode for high-energy-density Li metal batteries due to their high theoretical capacity (3860 mAh g−1) and low electrochemical potential (−3.04V versus standard hydrogen electrodes). Nonetheless, the inherent instability of Li metal against conventional carbonate-based electrolytes (denoted as carbonates), causing unpredictable reactions and unstable interphase layers, precludes the commercialization of Li metal batteries. Herein, an innovative strategy-hybrid polyion complex micelle to enable high-performance Li metal anodes in carbonates is reported. Ionized LiNO3 cooperates with block copolymer (polystyrene-block-poly(2-vinyl pyridine) (S2VP)) micelles via electrostatic interaction and plants on the Li metal surface together. The union with S2VP and ionized LiNO3 can shut off from contact with the Li surface and carbonates, construct the unique solid electrolyte interface layers with a Li-ion conductivity gradient, and control Li morphology. S2VP/LiNO3-Li metal electrodes enable high-efficiencies over 100 cycles and even at high-temperature with universal carbonates. S2VP/LiNO3-Li//LiNi0.8Co0.1Mn0.1O2 full cells achieve long-stable cycling over 300 cycles under harsh test conditions: limited-excess Li (thickness of 40 and 100 μm), high-areal capacity (4.0 mAh cm−2), and high-current density (4.0 mA cm−2). Moreover, a pouch-type full cell demonstrates commercial viability. This work provides new insights into enabling Li metal batteries with high-energy-density to adopt conventional carbonates.Data Availability: Data will be made available on request.

Акцент на инфузионную терапию полиионным сукцинат-метиониновым комплексом при терапии неалькогольной жировой болезни печени

Акцент на инфузионную терапию полиионным сукцинат-метиониновым комплексом при терапии неалькогольной жировой болезни печени

Influence of direct electric field on PMCG-alginate-based microcapsule

In this study, the influence of direct electric current on a microcapsule was investigated. The microcapsule consisted of a core from a calcium ion and sodium alginate (SA) complex and the microcapsule membrane was formed by the polyionic complexation of poly(methylene-co-guanidine) (PMCG) and cellulose sulfate (CS). Microcapsules showed swelling and decreasing mechanical properties under the applied electric current, and the microcapsule membrane showed anisotropic swelling on the electrode side. The effect is attributed to an electrokinetic phenomenon, predominant formation of hydroxyl ions, and the diffusion of hydrated ions. The swelling degree of the microcapsule and microcapsule membrane at different pH and the applied electric current under alkali and acidic conditions was investigated. The swelling degree was influenced by the dissociation of the membrane, which was observed after applying the electric field, which was caused by the electrokinetic effect and the neutralization of the polycation (under alkali conditions) or polyanionic (under acidic conditions) segment during membrane formation.

PH Responsive Strong Polyion Complex Shape Memory Hydrogel with Spontaneous Shape Changing and Information Encryption.

Polyion complex (PIC) hydrogels attract lots of studies because of the relatively definite network and excellent mechanical strength. However, the stability of the PIC hydrogel is poor in salt solutions due to the counter-ion screening effect, which restricts their applications. Besides, novel functions of the PIC hydrogels also need to be explored. In this work, a multifunctional PIC hydrogel is prepared by polymerizing a hydrophobic monomer 2-(diethylamino)ethyl methacrylate in poly(styrene sulfonic acid) aqueous solution with the presence of counter-ion NaCl. Fourier transform infrared (FTIR) spectra, water content, and mechanical properties of the hydrogel are investigated. The introduction of hydrophobic weak electrolyte into the hydrogel brings stable excellent mechanical strength even in NaCl solutions with high concentration and pH modulated softening and strengthening. Surprisingly, the hydrogel swells but is strengthened in HCl, while it shrinks but is softened in NaOH. pH induced shape memory and unique spontaneous shape changing is thus presented benefiting from this synergistic effect. Moreover, information encryption is realized on the PIC hydrogel owing to the transmittance change and the different water absorption capability of the hydrogel at different states. This new kind of PIC hydrogel proposes a new smart material in continuously actuating soft machines and secretive information transformation.