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Conducting hydrogels have attracted attention as a special functional class of smart soft materials and have found applications in various advanced fields. However, acquiring all the characteristics such as conductivity, adequate adhesiveness, self-healing ability, stretchability, biocompatibility, and stimulating deformation responsiveness still remains a challenge. Inspired by the mechanism of bioadhesion in marine mussels, a multifunctional nanocomposite hydrogel with excellent adhesiveness to a broad range of substrates including human skin was developed with the help of synergistic multiple coordination bonds between clay, poly(N-isopropylacrylamide) (PNIPAM), and polydopamine nanoparticles (PDA-NPs). The prepared hydrogel showed controllable near-infrared (NIR) responsive deformation after incorporation of PDA-NPs as highly effective photothermal agents in the thermo-sensitive PNIPAM network. Meanwhile, the fabricated nanocomposite hydrogels showed excellent stretchability and conductivity, which make them attractive material candidates for application in various fields, such as electronic skin, wearable devices, and so on., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A pH and redox dual stimuli-responsive poly(aspartic acid) derivative for controlled drug release was successfully developed through progressive ring-opening reactions of polysuccinimide (PSI). Polyethylene glycol (PEG) chains were grafted onto the polyaspartamide backbone via redox-responsive disulfide linkages, providing a sheddable shell for the polymeric micelles in a reductive environment. Phenyl groups were introduced into the polyaspartamide backbone via the aminolysis reaction of PSI to serve as the hydrophobic segment of micelles. The polyaspartamide scaffold was also functionalized with N-(3-aminopropyl)-imidazole to obtain the pH-responsiveness manifesting as a swelling of the core of micelles at a low pH. The polymeric micelles with a core-shell nanostructure forming in neutral media exhibited both pH and redox responsive characteristics. Doxorubicin (DOX) as a model drug was encapsulated into the core of micelles through both hydrophobic and π-π interactions between aromatic rings and the DOX-loaded polymeric micelles exhibited accelerated drug release behaviors in an acidic and reductive environment due to the swelling of hydrophobic cores and the shedding of PEG shells. Furthermore, the cytocompability of the polymer and the cytotoxicity of DOX-loaded micelles towards Hela cells under corresponding conditions were evaluated, and the endocytosis of DOX-loaded polymeric micelles and the intracellular drug release from micelles were observed. All obtained data indicated that the micelle was a promising candidate for controlled drug release., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In this paper, a doxorubicin delivery system is reported based on a pH-responsive zwitterionic polypeptide derivative. To improve the anti-protein-fouling capacity, the poly(amino acid) was modified by grafting short-chain zwitterions via aminolysis reaction of polysuccinimide with l-lysine. As a result, both positively and negatively charged moieties were introduced onto the same side chain in a simultaneous fashion, providing a nano-scale homogenous mixture of balanced charges. The zwitterionic side chains serve as hydrophilic segments in the copolymer and feature excellent resistance to nonspecific protein adsorption. Doxorubicin was chemically grafted onto the poly(amino acid) moiety through acid-labile hydrazone linkages, providing removable hydrophobic segments and driving the polymer self-assembly. Free doxorubicin could be encapsulated into the self-assembled micelles via hydrophobic interactions and molecular π-π stacking. The results obtained show that the drug loaded nanoparticles exhibit excellent stabilities in protein solutions at pH=7.4 and significantly enhanced drug release characteristics under acidic conditions. The cytotoxicity characteristics of the zwitterionic copolymer and drug-loaded nanoparticles at different pH values were investigated in vitro and feature an excellent biocompatibility and anti-cancer activity, respectively., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A pH- and thermo-responsive poly(amino acid)-based amphiphilic copolymer was developed, functioning as a tumour targeting drug delivery system with good biocompatibility and biodegradability. To provide multi-stimuli sensitivity characteristics to the poly(amino acid)s, the polyaspartamide scaffold has been functionalized with N,N-diisopropylamide groups via aminolysis reaction of polysuccinimide. PEG chains have also been chemically grafted to the poly(amino acid) backbone through acid-labile hydrazone linkages, providing a removable shield for the poly(amino acid) based nanoparticles. Furthermore, doxorubicin was chemically linked to the copolymer chain via hydrazone bonds, acting as the hydrophobic moiety to drive the polymeric self-assembly. Free doxorubicin molecules could be encapsulated into the self-assembled nanoparticles via hydrophobic interactions and molecular π-π stacking. The results obtained show that the drug release can be triggered by the temperature with a significantly increased release being observed under acidic conditions. The cytotoxicity behaviour of the copolymers and drug-loaded nanoparticles was investigated in vitro at varying pH values and different temperatures. In doing so, superior characteristics concerning compatibility and anti-cancer activity could be observed., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In an effort to prove the inherent side effects of doxorubicin (DOX) and potentially revoke the effects of drug resistance exhibited by cancer cells, we have designed a multifunctional DOX-delivery nano-carrier system able to encapsulate the drug resistance reversal agent Verapamil HCl (VRP·HCl). Hydrophilic short-chain polyethylene glycol (i.e., mPEG) was covalently linked to hydrophobic DOX and a benzoic imine linkage was used to form a linear amphiphilic PEGylated prodrug, namely mPEG-b-DOX. In aqueous solution, the amphiphilic PEG-b-DOX is able to self-assemble to form stable nanoparticles with a DOX loading content of approximately 40 wt% and a diameter of ∼ 143 nm. The resulting nanoparticles can simultaneously serve as an anticancer drug conjugate and as a drug carrier system. Here, the hydrophilic VRP could be encapsulated into the nano-carriers via a conventional dialysis method. The loading efficiency in mPEG-b-DOX nano-carrier was determined to be 53.97% and the loading content was found to be 7.71 wt%. The VRP-loaded nano-carriers grew slightly in size, to a diameter of ∼ 177 nm. We found that the release of DOX and VRP was much faster at a lower pH value. The biological activity of the nano-carriers were evaluated in vitro and compared with the DOX-loaded system. In doing so we found that the VRP-loaded nano-carrier features a much higher antitumor activity. Furthermore, the combined-system exhibits a significantly enhanced cytotoxicity with an elevated apoptosis rate observed for MCF-7/ADR used as a cell line in this in vitro study. This combinatory system and promising candidate for applications involving DOX chemotherapy proved to be easy to prepare and could be characterized in terms of biocompatibility, biodegradability, loading capacity, pH responsiveness and reversal of drug resistance., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A dually responsive nanocarrier with a multilayer core-shell architecture was prepared based on Fe3O4@SiO2 nanoparticles successively coated with poly(benzyl L-aspartate) (PBLA) and poly(ethylene glycol) (PEG) for the purpose of tumor specific drug delivery applications. In this system, PEG chains are connected to the surface via pH-sensitive benzoic-imine bonds and serve as a pH-sheddable hydrophilic corona. Meanwhile, the PBLA segments serve as a hydrophobic middle layer used to load the drugs via hydrophobic interactions. The Fe3O4@SiO2 nanoparticle functions as a superparamagnetic core used to direct the drug loaded nanocarrier to the target pathological site. The obtained materials were characterized with FT-IR, (1)H NMR, dynamic light scattering, zeta-potential, TEM, TGA, and hysteresis loop analysis. An anticancer drug doxorubicin (DOX) was selected as the model drug loaded into the nanocarrier, which was relatively stable under physiological conditions due to its neutral hydrophilic shell, and could quickly release the drug in response to increased acidity via shedding of the PEG shells through cleavage of the intermediate benzoic-imine bonds. Meanwhile, the neutral shell shedding would reveal a positively charged nanoparticle surface that is readily taken up by tumor cells. These pH- and magnetic-responsive nanoparticles showed significant potential for use in the targeted intracellular delivery of hydrophobic chemotherapeutics in cancer therapy., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Biodegradable shell cross-linked nanocapsules were prepared via layer-by-layer assembly of PADH (tertiary amine and hydrazide grafted polyaspartamide) and PACA (carboxyl and aldehyde grafted polyaspartamide) on silica spheres. Both of the polyaspartamide derivatives are water-soluble and biodegradable polymers with a protein-like structure, and obtained by aminolysis reaction of polysuccinimide. The latter is prepared by thermal polycondensation of aspartic acid. Dynamic light scattering and zeta potential measurements were used to analyze the layer-by-layer assembly process. Bovine serum albumin (BSA), as a model protein, was entrapped in the nanocapsules via electrostatic adsorption. Nanocapsules encapsulating BSA were prepared via layer-by-layer assembly on protein-entrapping amino-functionalized silica spheres, hydrazone cross-linking and silica core removal. The BSA release profiles exhibited a pH-dependent behavior. BSA release rate increased significantly as the ambient pH dropped from the physiological pH to acidic. Cell viability study suggests that the obtained polymeric nanocapsules have good biocompatibility. These kinds of novel composite nanocapsules may offer a promising delivery system for proteins., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A dually responsive nanocarrier with multilayer core-shell architecture was prepared based on Fe(3)O(4)@SiO(2) nanoparticles coated with mPEG-poly(l-Asparagine). Imidazole groups (pK(a)∼6.0) were tethered to the side chains of poly(l-Asparagine) segments by aminolysis. These nanoparticles were expected to be sensitive to both magnetic field and pH environment. The obtained materials were characterized with FTIR, dynamic light scattering, ζ-potential, TEM, TGA and hysteresis loop analysis. It was found that this Fe(3)O(4)@SiO(2)-polymer complex can form nano-scale core-shell-corona trilayer particles (∼250 nm) in aqueous solution. The Fe(3)O(4)@SiO(2), poly(L-Asparagine) and mPEG segments serve as a super-paramagnetic core, a pH-sensitive shell, and a hydrophilic corona, respectively. An antitumor agent, doxorubicin (DOX), was successfully loaded into the nanocarrier via combined actions of hydrophobic interaction and hydrogen bonding. The drug release profiles displayed a pH-dependent behavior. DOX release rate increased significantly as the ambient pH dropped from the physiological pH (7.4) to acidic (5.5). This is most likely due to protonation and a change in hydrophilicity of the imidazole groups in the poly(l-Asparagine) segments. This new approach may serve as a promising platform to formulate magnetic targeted drug delivery systems., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A novel zwitterionic polypeptide derivative, denoted as His-PAsp/PAsp, was successfully synthesized by amidation of Poly (α,β-L-aspartic acid) with L-histidine methyl ester. Turbidity, zeta potential and ¹H NMR measurements were used to study the aggregation behaviors of His-PAsp/PAsp under different pH values. The modified polypeptide derivative composed of electro-negatively carboxylic and electro-positively imidazole residues randomly so as to bear opposite charges at pH values above or below the isoelectric point. When the zwitterionic polypeptide was coated on silicon wafer as a model substrate material, the absorption resistance of fibrinogen, a blood protein resulting in the blood coagulation cascade, on the coated surface was measured. It was found that the adsorption amount of fibrinogen on the polypeptide-coated surface depended on the dose of the polypeptide on silicon wafer. Obvious resistance of the fibrinogen adsorption on the polypeptide-coated surface was observed. Since its good biodegradability and superior anti-protein-fouling property, this pH-responsive zwitterionic polypeptide is a promising candidate for surface modification in many biomedical applications, including medical implants, drug delivery carriers, and biosensors., (Copyright © 2011 Elsevier B.V. All rights reserved.)

A novel post-crosslinked polymeric adsorbent PDM-2 was prepared by Friedel-Crafts reaction of pendant vinyl groups without external crosslinking agent. Both the specific surface area and the pore volume of starting copolymer PDM-1 increased significantly after post-crosslinking. Batch adsorption runs of phenol from aqueous solution onto PDM-1 and PDM-2 were investigated. Commercial macroporous resins XAD-4 and AB-8 were chosen as the comparison. Experimental results showed that isotherms of phenol adsorption onto these four polymeric adsorbents could be represented by Freundlich model reasonably. PDM-2 exhibited higher adsorption capacity of phenol than other three adsorbents, which resulted from synergistic effect of larger specific surface area and polar groups on the network. The adsorption process for phenol was proved to be exothermic and spontaneous in nature. Thermodynamic parameters such as Gibb's free energy (DeltaG), change in enthalpy (DeltaH) and change in entropy (DeltaS) were calculated. Kinetics studies indicated that phenol uptake onto PDM-1 and PDM-2 followed the pseudo-second order model and the intraparticle diffusion process was a rate-controlling step. Column adsorption runs demonstrated that nearly 100% regeneration efficiency for PDM-2 by 3BV industrial alcohol and the adsorbate phenol can be easily recovered by further distilling. Continuous column adsorption-regeneration cycles indicated negligible capacity loss of PDM-2 during operation.

Poly(alpha,beta-L-aspartate) (PAsp) was partially esterified to afford an amphiphilic biodegradable polyanion, poly(sodium aspartate-co-propyl aspartate) (PAsp-Na/PAsp-P). The synthesized polyanion could be assembled into the nano-scaled aggregates in aqueous medium. The aggregate morphologies were studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) as a function of pH. It was demonstrated that micellization of this random copolymer occurred with stimulus of pH changes to form various morphological micelles. The copolymer existed as precipitate at low pH (pH<2). When pH increased to 4, the polymers were associated into spherical micelles with the core of poly(propyl aspartate) (PAsp-P) hydrophobic units and shell of some negatively charged poly(sodium aspartate) (PAsp-Na) units. At higher pH (pH>5), toroidal nanostructures of the micelles were formed because rigid polyamide chains directly assemble into the large hollow spheres. The CD study showed that the conformation underwent a transition between alpha-helix and random coil at pH 3-7. The cooperative transitions were regulated by the degree of ionization of carboxylic side chains. When they were protonated (neutralized), the molecular backbone was in favor of the regular helical structure; when deprotonated (ionized), the electrostatic repulsions among side chains destabilized the intramolecular hydrogen bonds, thus randomizing the regular conformation.