Poly Amino Research Articles

A diaminoethane motif bearing low molecular weight polymer as a new nucleic acid delivery agent

Among polymer-based gene delivery systems, poly(ethylene imine) (PEI) stands out as an effective polycation. However, the toxic effects of PEI especially at higher molecular weights limit its usage. Although the effects of PEI's architecture and molecular weight on gene delivery is controversial in literature, low molecular weight PEI appears to be efficient at transfection while having lower toxicity. Herein, as an alternative to low molecular weight, linear PEI, a methacrylate polymer bearing diamimoethane motifs, poly(2-((2-aminoethyl)amino)ethyl methacrylate) (P(AEAEMA)), was evaluated in vitro as a new nucleic acid delivery agent. P(AEAEMA) (8 kDa) showed low toxicity on Skov-3-luc and NIH/3T3 cell lines at polymer concentrations where PEI (8 kDa) was highly toxic. P(AEAEMA) could efficiently form complexes with siRNA at an N/P ratio of 2 as shown by gel electrophoresis. The diameter of P(AEAEMA)-siRNA complexes was found to be significantly lower than PEI-siRNA complexes almost at all tested N/P ratios. P(AEAEMA) could improve the stability of siRNA in serum containing media by protecting the siRNA against serum nucleases. siRNA and pDNA transfection efficiency of P(AEAEMA) on luciferase expressing Skov-3-luc cell line and HEK 293T cell line, respectively was found to be comparable to well-known nucleic acid carrier, PEI. The transfection efficiency of both P(AEAEMA) and PEI was found to be cell-type-dependent. None of the polymers were able to transfect MDA-MB-231 cells with siRNA or pDNA.

Water-based binder with easy reuse characteristics for silicon/graphite anodes in lithium-ion batteries

A new binder, poly(2-propenoic acid, 2-methyl-, 3-[(2-aminoethyl) amino]-2-hydroxypropyl ester) (P-HAEAPMA), is synthesized and applied to silicon/graphite (Si/graphite) anodes in lithium-ion batteries. The Si/graphite anode with the binder exhibits good electrochemical stability. Furthermore, the materials on the discarded Si/graphite/P-HAEAPMA electrode can be recycled for use based on water because the P-HAEAPMA binder is easily soluble in water. The discharge capacity and capacity retention rate of the electrode with reused materials are slightly lower than those of the original Si/graphite/P-HAEAPMA electrode. The binder is rich in polar amino and hydroxyl groups, which not only helps to form strong adhesion between the electrode active material and copper foil but also promotes the transport of Li ions. The electrochemical performance of the electrode with the P-HAEAPMA binder is significantly enhanced compared with that of the electrode with the traditional PVDF binder or water-based LA133 binder. After 305 cycles, a specific capacity of 485.0 mA h g−1 and a capacity retention rate of 74.8% are achieved for the Si/graphite/P-HAEAPMA electrode. A binder, poly(2-propenoic acid, 2-methyl-, 3-[(2-aminoethyl) amino]-2-hydroxypropyl ester) (P-HAEAPMA), is synthesized and applied to silicon/graphite anodes in lithium-ion batteries, which exhibits good electrochemical stability. After 305 cycles, a specific capacity of 485.0 mA h g−1 and a capacity retention rate of 74.8% are achieved. Moreover, the discarded electrode with P-HAEAPMA binder can be reused just based on water because the P-HAEAPMA binder is easily soluble in water, and the electrochemical properties of the electrode with reused materials are slightly lower than those of the original electrode.

Flexible, nonflammable, highly conductive and high-safety double cross-linked poly(ionic liquid) as quasi-solid electrolyte for high performance lithium-ion batteries

• Double cross-linking poly(ionic liquid)-based electrolyte is prepared by dual polymerization method. • Benefiting from ionic liquid, PIL-PEI 1 shows high flame-retardant. • Double cross-linking network endows lithium dendrite-resistant for PIL-PEI 1 electrolyte. • The package using liquid-free PIL-PEI1 as electrolyte can work in emergency situation. Liquid leakage and lithium dendrite growth are common safety hazards of lithium-ion batteries, and the application of quasi-solid electrolytes are considered to be the most promising material for inhibiting the safety problems. Herein, a new type of bi-functional ionic liquid is synthesized and polymerized into double cross-linked poly(ionic liquid) electrolyte (denoted as PIL-PEI) by dual cross-linking method [ring-opening polymerization network: epoxy groups in 1-vinyl-3-epoxypropylimidazolium bis(trifluoromethanesulfonyl)imide (VEIM-TFSI) cross-linked with amino-groups in poly(ethylene imine) (PEI), radical cross-linking network: VEIM-TFSI cross-linked with poly(ethylene glycol) diacrylate (PEGDA)]. The Double cross-linked network of PIL-PEI reveals satisfactory flexibility, thermal stability and remarkable electrochemical performances (room-temperature ionic conductivity, 1.03 × 10 −3 S cm −1 and lithium-ion transference number, 0.47). Furthermore, the compact network of PIL-PEI enables the formation of a strong solid electrolyte interface (SEI) layer on the lithium metal leading to the inhibition of lithium dendrite growth. As results, the batteries electrochemical performances, such as high charge/discharge capacity (165.6 mAh g −1 ), robust rate behavior (5.0C for 94 mAh g −1 ) and long-term lifespan (97.8% coulomb efficiency after 200 cycles) are significantly improved after assembled by LiFePO 4 -based cells equipping PIL-PEI as electrolyte. The soft package cell assembled with PIL-PEI is able to successfully light up the LED light and keep illuminating under varying hazardous situations such as bending and cutting, indicating that the PIL-PEI will have potential application value in highly secure flexible electronic devices.

Alternative method for trypsin-based cell dissociation using poly (amino ester) coating and pH 6.0 PBS

To maintain the cellular functions of a stem cells for therapeutic tissue engineering, an advanced cell culture method for safe cell dissociation is necessary. We developed a novel cell dissociation method by applying pH-responsive bioreducible polymer on the surface of tissue culture plates (TCPs). We applied acid-responsive bioreducible poly (amino ester) (PAE) as a new candidate for surface coating method to develop alternative cell dissociation method against conventional enzyme (trypsin-ethylene diamine tetra acetic acid (EDTA)) treatment. Human adipose derived stem cells (hADSCs) were cultured on and dissociated from PAE-coated TCPs to compare cell adhesion, cell proliferation, cell viability, and functionality to those of the cells cultured on and dissociated with trypsin-EDTA from normal TCPs without PAE coating. To confirm the in vivo therapeutic efficacy of the hADSCs retrieved from PAE-coated TCPs compared to that of the cells retrieved from normal TCPs with trypsin-EDTA, we induced skin defects at the dorsal area of mice and injected the cells collected from both conditions. With the PAE coating method, cell adhesion, cell proliferation, cell viability, and functionality, especially the angiogenic efficacy, were well preserved when compared to those of the cells treated with trypsin-EDTA. In addition to in vitro results, injecting hADSCs retrieved from PAE-coated TCPs showed similar in vivo angiogenesis and wound closing efficiency compared to those of injecting hADSCs retrieved from normal TCPs with trypsin-EDTA treatment at 2 weeks after the transplantation into mouse skin wound models. We proposed the alternative method for the cell dissociation with pH-responsive bioreducible polymer, PAE. This PAE coating method may lead to the development of alternative cell dissociation method without using enzyme for future regenerative medicine and stem cell therapy.

Biological evaluation of the modified nano-amorphous phosphate calcium doped with citrate/poly-amino acid composite as a potential candidate for bone repair and reconstruction

Large numbers of research works related to fabricating organic–inorganic composite materials have been carried out to mimic the natural structure of bone. In this study, a new modified n-ACP doped with citrate (n-ACP-cit)/poly (amino acids) (PAA) composite (n-ACP-cit/PAA) was synthesized by employing high bioactive n-ACP-cit and the biodegradable and biocompatible PAA copolymer. Its basic structure was characterized by X-ray diffraction spectroscopy, Fourier transformed infrared spectroscopy, and X-ray photoelectron spectroscopy. Moreover, the degradability, bioactivity, biocompatibility, and osteoconductivity of n-ACP-cit/PAA composite were evaluated in vitro and in vivo, using simulated body fluid (SBF) solution soaking test, mouse bone marrow mesenchymal stem cells proliferation and differentiation, morphological observation test, expression of genes associated with osteogenesis, and bone defect model repair test, respectively. The modified n-ACP-cit/PAA composite exhibited a much higher weight loss rate (36.01 wt.%) than that of PAA (23.99 wt.%) after immersing in SBF solution for 16 weeks and the pH values of local environment restored to neutral condition. Moreover, cells co-culturing with composites exhibited higher alkaline phosphatase activity, more calcium nodule-formation, and higher expression levels of osteogenic differentiation-related genes (Bmp-2, Colla I, OCN, OPN, and Runx-2) than that of PAA. Furthermore, the bone defect model repair test revealed that the composite could be intimately incorporated with the surrounding bone without causing any deleterious reaction and capable of guiding new bone formation. Together, these results indicated that the new modified bone repair n-ACP-cit/PAA composite material with specific characteristics may be designed for meeting diverse requirements from biomedical applications.

Catalase-conjugated surfaces: H2O2 detection based on quenching of tryptophan fluorescence on conducting polymers

Conducting polymers are promising materials used to prepare electrochemical and optical detection platforms for bioanalytical systems. After conjugation of biomolecules onto electropolymerized monomers for preparation of multifunctional surfaces, they can be used to easily monitor small molecules, macromolecules, and cells. In this study, multifunctional monomer with indole (necessary for fluorescence detection of H2O2) and carboxyl functional groups (necessary for covalent immobilization of biological material) was synthesized, electropolymerized, modified with biomolecules (catalase) and then applied for the selective detection of target analyte (H2O2). Tryptophan sequestered dithione [3,2-b:2′,3′-d] pyrrole (DTP-Trp) was synthesized and electropolymerized on indium tin oxide (ITO) coated polyethylene terephthalate (PET) substrates, which is a transparent support. Afterward, catalase (CAT) was immobilized on the Poly(DTP-Trp) using a zero-length crosslinker, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), via covalent bonds between carboxyl groups of CAT and amino groups of Poly(DTP-Trp). Surface characterization of Poly(DTP-Trp)/CAT was done by scanning electron microscopy (SEM) and energy dispersive x-ray analysis (EDX). The presence of Poly(DTP-Trp)/CAT on ITO-PET surfaces were also confirmed by electrochemical methods to show the success of support modification. Determination of H2O2 was investigated using fluorescence spectrometry based on quenching mechanism of H2O2 on the fluorescence of tryptophan. After optimization of working conditions of Poly(DTP-Trp)/CAT, H2O2 detection in synthetic samples was done without any interference of the matrices.

Current Diagnostic Techniques used to detect SARS-COV-2- Coronavirus

The corona virus disease being aware commonly as Covid-19 in passing days among common masses is a novel viral illness of the systema respiratorium, causing a sustained pandemic which is in particular characterized by atypical pneumonia with specific symptoms of mild fever, runny nose with secreted fluid similar to flu, hypoxia, myalgia, anosmia, ageusia, shortness of breath, normal or decreased leukocyte count, ground glass opacities, sore throat and cough without phlegm. It is caused by an epidemic referred as SARS CoV-2 with abbreviation of severe acute respiratory syndrome coronavirus-2 nowadays. The procedures to be adopted for the diagnosis of COVID-19 should be based not only on clinical but epidemiological agents also and anyways stand on the link to an assessment and likelihood of the infection. The SARS CoV-2 is diagnosed with different test techniques like serological, molecular and others but most common for it is RT-PCR which is widely used and most reliable one to authenticate the findings of this disease. In the earlier times its detection was too an issue but luckily soon after its threat the scientists and organizations involved themselves and developed strong techniques to get reliable and accurate results with peaceful outcomes. The including such techniques are like immunological assay, amplification technique like RT-PCR (Spin column-and poly amino ester magnetic nanoparticle (pcMNPs) extraction method. Real-time nanopore target sequencing (NTS) and amplification methods) while on the other hands latest in use techniques are Isothermal nucleic acid amplification (as their subcategories include transcription-mediated amplification (TMA), Loop-mediated isothermal amplification (LAMP), rolling circle amplification (RCA) and clustered regularly interspaced short palindromic repeats (CRISP), and TMA assay). The novel techniques developed for this particular purpose are Biosensors, Localized surface plasma resonance (LSPR) sensor, the Field effect transistor (FET) and Cell-based potentiometric biosen.

Facile preparation of tertiary amine grafted poly (α,β-L-aspartic acid) with zwitterionic property to limit nonspecific protein adsorption

A series of poly (amino acid) with zwitterionic character was prepared for surface coating to avoid protein adsorption, by modifying the poly (aspartic acid) side chain with tertiary amine groups. An interesting and facile procedure is described with starts with polysuccinic acid which is followed by ring-opening with amino functions and finally hydrolysis of the remaining succinic acid groups achieving the polyaspartic acid structure as backbone. The degree of cationic tertiary amino group was easily varied by the degree of ring-opening with amines. The materials show isoelectric point between pH 4 and 9, have a typical zwitterionic character, and can be used to coat negatively as well as positively charged surfaces, depending on composition. The protein adsorption behavior is thus pH dependent and was studied with various proteins mainly available in blood. The adsorption test proved that a significant reduction of protein adsorption could be found for fibrinogen and albumin, and this protein-repellent behavior is strongly dependent on the amount of the absorbed polymer (adsorbed at pH = 7.4). This is a nice additional contribution to polymers with zwitterionic character used as coating reducing nonspecific protein adsorption.

Experimental Investigation of Epoxy/Poly(amino amide)/Phthalic Anhydride: Mechanical Properties and Thermal Stability

Epoxy resin is one of materials engineering that is widely applied especially in the shipping industry, aviation, automotive, and others. With a variety of applications led many scientists in the field of materials engineering work to improve the properties and ability of the epoxy either by changing the structure of epoxy. One way to improve the properties of epoxy is adding certain compounds that can react and able to change the properties of the epoxy according to the requirement. In this study, to improve the properties of the epoxy, then added phthalic anhydride compounds. The epoxy was cured using poly(amino amide) (PAA) as hardener at 40 wt%. The composition of phthalic anhydride (PA) was added at 5, 10, 15 and 20 wt%. The epoxy/PAA/PA was evaluated as the effect of phthalic anhydride composition. The addition of phthalic anhydride increase the elongation at break, energy and impact strength but decreased tensile strength and thermal stability. The optimum of energy and impact strength was at 20 wt% phthalic anhydride respectively 0.398 J and 5450,48 J/m2 The addition of phthalic anhydride decrease the thermal properties of epoxy/PAA/PA. Stability of the lowest in the addition of 15 wt% PA around 146 °C.

A Reactive Oxygen Species-Responsive Poly(amino acids) Nanoparticle Loading Doxorubicin for Glioblastoma Multiforme Treatment.

Amino acids are significant for human life and therefore considered as the crucial nutrients for human body with high biosafety. Due to their high biocompatibilities and various physicochemical properties, their polymers can be applied to construct drug delivery systems for various diseases' treatments. Among them, glioblastoma multiforme received special attention and numerous efforts regarding to nanotechnology were developed to treat such tumor. However, the biosafety of the delivering materials in those efforts arises as a critical issue in consideration of the weak patients. Therefore, a ROSresponsive nanoparticle (DOX@PLSPL) with poly(amino acids) encapsulating doxorubicin was developed for glioblastoma multiforme treatment. DOX@PLSPL was constructed by poly-lysine and poly-leucine with high biocompatibility. The high doxorubicin encapsulation efficiency and the controlled release manner of DOX@PLSPL ensured its high anti-tumor effect. Totally, this DOX@PLSPL can be used as a promising drug delivery system for glioblastoma multiforme treatments.

Chemical functionalization of Cellulose-poly(glycidyl-methacrylate) graft copolymer with two different poly amino compounds

Two amino-functionalized cellulose-poly(glycidyl methacrylate) graft copolymers (AM-CPGMA), based on waste cotton fibers, were preparedby the aminization of selected cellulose-poly(glycidyl methacrylate) graft copolymer (CPGMA) produced at best polymerization conditions using diethylenetri-amine (DETA) and triethylenetetraamine (TETA). The different aminization parameters, namely the aminating agent/epoxy molar ratio, reaction time, liquor ratio, pHand temperature were investigated, and optimum reaction conditions were established. The two prepared amino-functionalized cellulose-poly(glycidyl methacrylate) graft copolymers (AM-CPGMA) were characterized by the FT-IR, thermal gravimetric analysis (TGA), surface area measurement using Brunauer–Emmett–Teller (BET) and Barrett-Joyner-Halenda (BJH) theories and scanning electron microscope (SEM). Thus obtained results were compared with the native cellulose and its graft copolymer.

Synthesis of Poly-Amino Acid Ionic Liquid Up-Conversion Fluorescent Probe and its Application in Fe(II)/Fe(III) Speciation Analysis.

The poly amino acid ionic liquid (poly-1-vinyl-3-butylimidazolium glutamate acid, p-1-VbmGlu), with a stable up-conversion fluorescence(UCF) probe, was firstly prepared and the synthesis conditions were optimized. The UCF were found to be specifically quenched by Fe(III), but not respond to Fe(II). In H2O2 medium, Fe(II) posed strong quenching effect on the UFC owing to Fe(III) produced by redox between H2O2.and Fe(II). Therefore p-1-VbmGlu was employed as a UFC for Fe(II)/Fe(III) speciation analysis under the control of H2O2. The detection limits of Fe(II)/Fe(III) were 6.16ng/mL and 4.48ng/mL, with relative standard deviations of 1.1% and 2.0%, respectively. This method was successfully utilized in the analysis of Fe(II)/Fe(III) in multiple real samples.

Two-dimensional infrared spectral explorations into bilayer and monolayer self-assemblies of amphiphilic polypeptides

Poly(2-(3-((2-hydroxyethyl)amino)-3-oxopropyl)ethyleneamido) (PHAOE) is an amphiphilic polypeptide. The self-assembly is significant, but the ultrafast dynamic analyses of the peptide self-assembly are exiguous and worth further exploring. In this investigation, the temporal dynamic characteristics of the aggregates and unaggregated PHAOEs are mined by the two-dimensional infrared (2D IR) spectroscopy. The homogeneous and inhomogeneous diffusion processes of the carbonyl stretching modes of the unaggregated PHAOEs are slower than those of the self-assemblies. The inhomogeneous spectral diffusion proportion of the biopolymer PHAOE in methanol is greater than that in dimethyl sulfoxide (DMSO). The solvation shells surround the aggregates and unaggregated PHAOEs in the protic solvent methanol, but there are not any solvation shells around the aggregates or unaggregated PHAOEs in the dipolar solvent DMSO. The massive hydrogen-bonded monolayer self-assembly has merely an aggregate of PHAOEs and no solvation shell in DMSO. But the hydrogen-bonded bilayer self-assembly has a self-assembled methanol shell and an interior aggregate of PHAOEs in methanol. The self-assemblies of PHAOEs motivate the methanols to self-assemble. The large delocalized amide structure results in the fast spectral diffusion of the carbonyl stretching mode.Communicated by Ramaswamy H. Sarma

Palladium nanoparticles decorated on a novel polyazomethine as a highly productive and recyclable catalyst for Suzuki coupling reactions and 4-nitrophenol reduction

This report displays the procedure in preparation of fast, highly productive, reusable, and easily retrievable Pd nanoparticles (NPs) as a heterogeneous catalyst (Pd NPs@P(3-MPAP)) immobilized on a novel polyazomethine with phenol group, Poly(3-methyl-4-((pyridin-2-ylmethylene)amino)phenol) (P(3-MPAP)), and the investigation of its catalytic efficiency in fabrication of several biaryl compounds by Suzuki coupling reactions and reduction of 4-nitrophenol to 4-aminophenol. The structures of the synthesized monomer, polymer support material and nanocatalyst were identified by UV–Vis, FT-IR, 1H NMR, TGA, XRD, SEM and EDS methods. The catalytic activity of Pd NPs@P(3-MPAP) catalyst in the synthesis of various biaryls by Suzuki coupling reactions was explored using microwave irradiation, which is rapid, easy, solventless and environmentally friendly method. The nanocatalyst presented outstanding advantageous methodology containing easy work-up with high reaction yield (99%) at very short reaction time (5 min) in solventless media using very low catalyst loading (0.007 mol%) in the synthesis of biaryls. Additionally, the harmful 4-nitrophenol was completely reduced to industrially useful 4-aminophenol in the presence of Pd NPs@P(3-MPAP) with low catalyst amount (1 mg), at very short reaction time (60s) without any toxic solvent (in water) at room temperature. Additionally, reproducibility test results for both catalytic reactions show that the highly productive nanocatalyst was easily retrievable and reusable for six and five sequential cycles, respectively, for Suzuki coupling reactions and reduction of 4-NP without any notable loss in its catalytic activity.

Preparation and application of a highly sensitive conjugated polymer-copper (Ⅱ) composite fluorescent sensor for detecting hydrazine in aqueous solution

At first, a conjugated polymer (poly(2,5-bis(4-(bis(pyridin-2-ylmethyl)amino) butoxyl)-1,4-Phenylethynylene-1,4-poly(phenylene ethynylene), PPE-DPA) was synthesized based on our earlier report. In this work, a highly selective and sensitive composite fluorescent sensor (PPE-DPA-Cu2+), which was PPE-DPA complexed with copper ions, has been developed and used to measure trace amounts of hydrazine in environmental water samples. The experiment conditions were investigated. Under optimized conditions, the sensor shows satisfactory detection performance, which can highly sensitively detect hydrazine with a linear range of 0–70 nmol L−1 and detection limit as low as 5.4 × 10−10 mol L−1 (S/N = 3). Meanwhile, the sensor exhibits high selectivity and strong anti-interference ability for various cations, anions, common reducing agents and organic amines. This sensor has been applied to detect hydrazine in the real water samples, and the recovery of hydrazine was 92.3%–112.0% after added standard solution of hydrazine. Satisfactory results indicate that the sensor is expected to be utilized for quantitative detection of hydrazine in environmental samples.

Amino-substituted naphthalene sulfonic acid/graphene composite as metal -free catalysts for oxygen reduction reactions

Composites of reduced graphene oxide (rGO) and conducting polymers synthesized from 8-amino-2-naphthalene sulfonic acid (8-ANSA), 5-amino-1-naphthalene sulfonic acid (5-ANSA), 2-amino-1-naphthalene sulfonic acid (2-ANSA), and 4-amino-1-naphthalene sulfonic (4-ANSA) were prepared for use as an electrocatalyst in oxygen reduction reaction (ORR). The electrocatalytic activities were examined in oxygen saturated 0.1 M KOH solution using cyclic and linear sweep voltammetry. The best performing polymer composite was found to be GC/poly(8-ANSA)/rGO, with an enhanced electrocatalytic activity over the rGO only and poly(8-ANSA) only films. More than 100 mV positive shift in the onset potential and 1.6 times increase in current density were observed. The catalytic activity of 2-ANSA, 4-ANSA, 5-ANSA, and 8-ANSA was also validated by density functional theory (DFT). Our calculations predict a much better catalytic activity for 8-ANSA than that of 2-ANSA, 4-ANSA, and 5-ANSA. KEY WORDS : Poly(amino naphthalene sulfonic acid), Reduced graphene oxide, Oxygen reduction reaction, Electrocatalyst Bull. Chem. Soc. Ethiop. 2019 , 33(2), 359-372. DOI: https://dx.doi.org/10.4314/bcse.v33i2.16

Poly(amino acid)/ZnO nanoparticles nanocomposites with enhanced thermal, mechanical, and antibacterial properties

Poly(amino acid) (PAA)-based nanocomposites were synthesized by in situ melting polycondensation with addition of different contents of ZnO nanoparticles (ZnO NPs); the morphology and thermal, mechanical, cytotoxicity, antibacterial and dielectric properties of the resulting nanocomposites were investigated and characterized. The nanoparticles were dispersed within the matrix without the need for coupling agent and surfactants. The crystallization temperature had a gradual rise with increasing ZnO NP loading, confirming that the nanoparticles act as nucleating agents for PAA crystallization. The nanoparticles increased the thermal stability of the matrix. The mechanical properties were gradually enhanced by increasing the ZnO NP content except for the elongation at break, which showed its highest value at 1 wt% ZnO NP contents. They also exhibited active inhibition against both Gram-positive and Gram-negative bacteria, which was gradually enhanced with increase in ZnO NP content. Meanwhile, the nanocomposites showed no obvious cytotoxicity. Thus, these nanocomposites are suitable as performance materials in the field of medical apparatus.

Design of an Amphiphilic Poly(aspartamide)-mediated Self-assembled Nanoconstruct for Long-Term Tumor Targeting and Bioimaging.

Biodegradable polymers have been developed for the targeted delivery of therapeutics to tumors. However, tumor targeting and imaging are usually limited by systemic clearance and non-specific adsorption. In this study, we used poly(amino acid) derivatives, such as poly(succinimide), to synthesize a nanomicelle-forming poly(hydroxyethylaspartamide) (PHEA, P) modified sequentially with octadecylamine, polyethylene glycol (PEG, P), and glycine (G) to design PHEA-PEG-glycine (PPG) nanoparticles (NPs). These PPG NPs were further tethered to cyclic Arg-Gly-Asp (cRGD) sequences for formulating tumor-targeting PPG-cRGD NPs, and then loaded with IR-780 dye (PPG-cRGD-IR-780) for visualizing tumor homing. cRGD cloaked in PPG NPs could bind specifically to both tumor endothelium and cancer cells overexpressing αvβ3 integrins. PPG-cRGD NPs exhibited enhanced physiological stability, cellular viability, and targeted intracellular uptake in cancer cells. In addition, PPG-cRGD NPs offered enhanced systemic circulation, leading to preferential tumor targeting and prolonged fluorescence tumor imaging for nearly 30 days. Nevertheless, non-targeted formulations demonstrated premature systemic clearance with short-term tumor imaging. Histochemical analysis showed no damage to normal organs, reaffirming the biocompatibility of PHEA polymers. Overall, our results indicated that PPG-cRGD NPs, which were manipulated to obtain optimal particle size and surface charge, and were complemented with tumor targeting, could improve the targeted and theranostic potential of therapeutic delivery.

Tunable nonenzymatic degradability of N-substituted polyaspartamide main chain by amine protonation and alkyl spacer length in side chains for enhanced messenger RNA transfection efficiency

ABSTRACT Degradability of polycations under physiological conditions is an attractive feature for their use in biomedical applications, such as the delivery of nucleic acids. This study aims to design polycations with tunable nonenzymatic degradability. A series of cationic N-substituted polyaspartamides were prepared to possess primary amine via various lengths of alkyl spacers in side chains. The degradation rate of each polyaspartamide derivative was determined by size exclusion chromatography under different pH conditions. The N-substituted polyaspartamide containing a 2-aminoethyl moiety in the side chain (PAsp(AE)) showed considerable degradability under physiological conditions (pH 7.4, 37 °C). In contrast, the N-substituted polyaspartamides bearing a longer alkyl spacer in the side chain, i.e. the 3-aminopropyl (PAsp(AP)) and 4-aminobutyl moieties (PAsp(AB)), more strongly suppressed degradation. Further, a positive correlation was observed between the degradation rate of N-substituted polyaspartamides and a deprotonation degree of primary amines in their side chains. Therefore, we conclude that the deprotonated primary amine in the side chain of N-substituted polyaspartamides can induce the degradation of the main chain through the activation of amide nitrogen in the side chain. When N-substituted polyaspartamides were utilized as a messenger RNA (mRNA) delivery vehicle via formation of polyion complexes (PICs), degradable PAsp(AE) elicited significantly higher mRNA expression efficiency in cultured cells compared to PAsp(AP) and PAsp(AB). The higher efficiency of PAsp(AE) might be due to the facilitated destabilization of PICs within the cells, directed toward mRNA release. Additionally, degradation of PAsp(AE) considerably reduced its cytotoxicity. Thus, our study highlights a useful design of well-defined cationic poly(amino acid)s with tunable nonenzymatic degradability.

Reconstruction of calvarial bone defects using poly(amino acid)/hydroxyapatite/calcium sulfate composite

The aim of this study was to evaluate the thermal properties and in vivo interface performance of poly(amino acid) (PAA) and a composite containing PAA, hydroxyapatite (HA), and calcium sulfate (CS), with respect to their suitability for skull repair. Biocompatibility was evaluated by implantation of materials into muscles of rabbits for eight weeks. Skull repair was assessed by implanting PAA, the compact PAA/HA/CS composite (c-PAA/HA/CS), and a one-side-porous PAA/HA/CS composite (p-PAA/HA/CS) into rabbit calvarial defects. The results showed that the PAA/HA/CS composite possessed good heat resistance and possessed excellent biocompatibility and osteoconductivity. Guided bone regeneration and calvarial repair were observed, with excellent integration between calvarial tissue and implant. The p-PAA/HA/CS composite performed best in terms of stability and bone bonding between implant and host bone tissue. Thus, the present work provides new information for the potential use of osteoconductive PAA/HA/CS composites with a macrostructure in calvarial bone repair.