High-Strength, Freeze-Resistant, Recyclable, and Biodegradable Polyvinyl Alcohol/Glycol/Wheat Protein Complex Organohydrogel for Wearable Sensing Devices.

The application of flexible wearable sensing devices based on conductive hydrogels in human motion signal monitoring has been widely studied. However, conventional conductive hydrogels contain a large amount of water, resulting in poor mechanical properties and limiting their application in harsh environments. Here, a simple one-pot method for preparing conductive hydrogels is proposed, that is, polyvinyl alcohol (PVA), wheat protein (WP), and lithium chloride (LiCl) are dissolved in an ethylene glycol (EG)/water binary solvent. The obtained PVA/EG/WP (PEW) conductive organohydrogel has good mechanical properties, and its tensile strength and elongation at break reach 1.19 MPa and 531%, respectively, which can withstand a load of more than 6000 times its own weight without breaking. The binary solvent system composed of EG/water endows the hydrogel with good frost resistance and water retention. PEW organohydrogel as a wearable strain sensor also has good strain sensitivity (GF = 2.36), which can be used to detect the movement and physiological activity signals in different parts of the human body. In addition, PEW organohydrogels exhibit good degradability, reducing the environmental footprint of the flexible sensors after disposal. This research provides a new and viable way to prepare a new generation of environmentally friendly sensors.

Preparation of intravenous injection nanoformulation via co-assemble between cholesterylated gemcitabine and cholesterylated mPEG: enhanced cellular uptake and intracellular drug controlled release.

The objective of this study was to prepare the CHS-mPEG/CHS-dFdC nanoformulation could be administrated through intravenous injection in nude mice. Particularly, CHS-mPEG was selected to co-assemble with CHS-dFdC to improve the prodrug concentration and enhance the stability of nanoformulation. The nanoformulation could be prepared by codissolution-coprecipitation. All of the nanoformulations kept stable in PBS at 4 °C or simulative human plasma at 37 °C. As molar ratios of CHS-mPEG1900/CHS-dFdC increased from 0.1/1 to 2/1, the weight concentration of CHS-dFdC increased from 2.5 to 15 mg/mL. It was found the optimal CHS-mPEG1900/CHS-dFdC nanoformulation displayed controlled drug release in simulative lysosome condition. The amount of released dFdC reached up to 90% within 10 h. It also exhibited enhanced cellular uptake ability, 7-folds higher than that of dFdC during 2.5 h incubation. And it showed superior cytotoxicity resulted from the enhanced cellular uptake ability on BxPC-3 cells.

Magnetic resonance tracking of endothelial progenitor cells labeled with alkyl-polyethylenimine 2 kDa/superparamagnetic iron oxide in a mouse lung carcinoma xenograft model.

The potential of using endothelial progenitor cells (EPCs) in novel anticancer therapy and the repair of vascular injury has been increasingly recognized. In the present study, EPCs were labeled with N-alkyl-polyethylenimine 2 kDa (PEI2k)-stabilized superparamagnetic iron oxide (SPIO) to facilitate magnetic resonance imaging (MRI) of EPCs in a mouse lung carcinoma xenograft model. EPCs derived from human peripheral blood were labeled with alkyl-PEI2k/SPIO. The viability and activity of labeled cells were evaluated using proliferation, migration, and tubulogenesis assays. Alkyl-PEI2k/SPIO-labeled EPCs were injected intravenously (group 1) or mixed and injected together with A549 cells subcutaneously (group 2) into groups of six mice with severe combined immunodeficiency. The labeling efficiency with alkyl-PEI2k/SPIO at 7 µg Fe/mL concentration was approximately 100%. Quantitative analysis of cellular iron was 6.062 ± 0.050 pg/cell. No significant effects on EPC proliferation, migration, or tubulogenesis were seen after labeling. Seven-tesla micro-MRI showed the presence of schistic or linear hypointense regions at the tumor margins starting from days 7 to 8 after EPC administration. This gradually extended into the inner tumor layers in group 1. In group 2, tumor growth was accompanied by dispersion of low-signal intensity regions inside the tumor. Iron-positive cells identified by Prussian blue dye were seen at the sites identified using MRI. Human CD31-positive cells and mouse CD31-positive cells were present in both groups. Labeling EPCs with alkyl-PEI2k/SPIO allows noninvasive magnetic resonance investigation of EPC involvement in tumor neovasculature and is associated with excellent biocompatibility and MRI sensitivity.

Polyvinyl alcohol/chitosan based nanocomposite organohydrogel flexible wearable strain sensors for sports monitoring and underwater communication rescue.

Hydrogel-based flexible wearable sensors have garnered significant attention in recent years. However, the use of hydrogel, a biomaterial known for its high toughness, environmental friendliness, and frost resistance, poses a considerable challenge. In this study, we propose a stepwise construction and multiple non-covalent interaction matching strategy to successfully prepare dynamically physically crosslinked multifunctional conductive hydrogels. These hydrogels self-assembled to form a rigid crosslinked network through intermolecular hydrogen bonding and metal ion coordination chelation. Furthermore, the freeze-thawing process promoted the formation of poly(vinyl alcohol) microcrystalline domains within the amorphous hydrogel network system, resulting in exceptional mechanical properties, including a tensile strength (2.09 ± 0.01 MPa) and elongation at break of 562 ± 12 %. It can lift 10,000 times its own weight. Additionally, these hydrogels exhibit excellent resistance to swelling and maintain good toughness even at temperatures as low as -60 °C. As a wearable strain sensor with remarkable sensing ability (GF = 1.46), it can be effectively utilized in water and underwater environments. Moreover, it demonstrates excellent antimicrobial properties against Escherichia coli (Gram-negative bacteria). Leveraging its impressive sensing ability, we combine signal recognition with a deep learning model by incorporating Morse code for encryption and decryption, enabling information transmission.

Active self-assembly of piezoelectric biomolecular films via synergistic nanoconfinement and in-situ poling.

Piezoelectric biomaterials have attracted great attention owing to the recent recognition of the impact of piezoelectricity on biological systems and their potential applications in implantable sensors, actuators, and energy harvesters. However, their practical use is hindered by the weak piezoelectric effect caused by the random polarization of biomaterials and the challenges of large-scale alignment of domains. Here, we present an active self-assembly strategy to tailor piezoelectric biomaterial thin films. The nanoconfinement-induced homogeneous nucleation overcomes the interfacial dependency and allows the electric field applied in-situ to align crystal grains across the entire film. The ß-glycine films exhibit an enhanced piezoelectric strain coefficient of 11.2 pm V-1 and an exceptional piezoelectric voltage coefficient of 252 × 10-3 Vm N-1. Of particular significance is that the nanoconfinement effect greatly improves the thermostability before melting (192 °C). This finding offers a generally applicable strategy for constructing high-performance large-sized piezoelectric bio-organic materials for biological and medical microdevices.

Van der Waals Exfoliation Processed Biopiezoelectric Submucosa Ultrathin Films.

Piezoelectric biomaterials have attracted significant attention due to the potential effect of piezoelectricity on biological tissues and their versatile applications. However, the high cost and complexity of assembling and domain aligning biomolecules at a large scale, and the disordered arrangement of piezoelectric domains as well as the lack of ferroelectricity in natural biological tissues remain a roadblock toward practical applications. Here, utilizing the weak van der Waals interaction in the layered structure of small intestinal submucosa (SIS), a van der Waals exfoliation (vdWE) process is reported to fabricate ultrathin films down to the thickness of the effective piezoelectric domain. Based on that, the piezoelectric property is revealed of SIS stemming from the collagen fibril, with piezoelectric coefficients up to 4.1 pm V-1 and in-plane polarization orientation parallel to the fibril axis. Furthermore, a biosensor based on the vdWE-processed SIS film with an in-plane electrode is demonstrated that produces open-circuit voltages of ≈250 mV under the cantilever vibration condition. The vdWE method shows great potential in facilely fabricating ultrathin films of soft tissues and biosensors.

High-throughput dielectrophoretic manipulation of bioparticles within fluids through biocompatible three-dimensional microelectrode array.

Dielectrophoresis (DEP) has been deemed as a potential and ideal solution for bioparticle manipulation. A 3-D carbon micro-electro-mechanical system (MEMS) fabricated from the latest developed carbon-MEMS approach has advantages of offering low-cost, biocompatible and high-throughput DEP manipulation for bioparticles. In this paper, a typical process for fabrication of various 3-D microelectrode configurations was demonstrated; accurate numerical analysis was presented on electric field gradient distribution and DEP force based on various microelectrode array configurations. The effects of electrode edge angle, electrode edge-to-edge spacing and electrode height on the electric field distributions were investigated, and optimal design considerations and rules were concluded through analysis of results. The outcomes demonstrate that the sharp edge electrode is more effective in DEP manipulation and both electrode edge-to-edge spacing and electrode height are critical design parameters for seeking optimal DEP manipulation. The gradient magnitude increases exponentially as the electrode spacing is reduced and the electric field extends significantly as the electrode height increases, both of which contribute to a higher throughput for DEP manipulation. These findings are consistent with experimental observations in the literature and will provide critical guidelines for optimal design of DEP devices with 3-D carbon-MEMS.

4-Carboxyphenylboronic acid-decorated, redox-sensitive rod-shaped nano-micelles fabricated through co-assembling strategy for active targeting and synergistic co-delivery of camptothecin and gemcitabine.

To achieve redox-controlled and tumor active targeting synergistic self-delivery of camptothecin and gemcitabine, redox-sensitive rod-shaped nano-micelles are fabricated through co-assembling between camptothecin-disulfide bond-PEG2000-4-carboxyphenylboronic acid and camptothecin-disulfide bond-gemcitabine conjugate. Most of all, for multidrug resistant cancer cell line MCF-7/ADR which is more resistant against CPT, increasing content of CPT in the formulation is favorable for synergistic effect of CPT and GEM drug combination. Benefiting from simple co-assembling strategy, it is easy and convenient to adjust drug ratio of CPT/GEM to optimize the synergism of drug combination. In addition, nano-micelles fabricated from co-assembling are endowed with both high absolute drug concentration and enhanced colloidal stability, which is helpful to in vivo studies. Transmission electron microscopy observation confirmed the rod-shaped morphology, which is beneficial to cellular internalization, of co-assembled nano-micelles resulting from π-π stacking interactions of CPT moieties and appropriate hydrophilic and hydrophobic interactions during co-assembling. Taking advantages of the specific interactions between 4-carboxyphenylboronic acid and sialic acid, co-assembled nano-micelles exerted enhanced cellular internalization. Noteworthy, compared with cocktail mixture of free CPT and GEM, nano-micelles greatly alleviated drug reflux against MCF-7/ADR and 4T1 cells. The nano-micelles realized redox-controlled ratio-metric and synchronous delivery of CPT and GEM, thereby pronounced in vitro synergistic antiproliferative effect against MCF-7/ADR and 4T1cells. Furthermore, in vivo bio-distribution analysis indicated the preferential accumulation of nano-micelles at tumor site, which could increase therapeutic efficacy and decrease side effects of non-selective anticancer drugs. Taken together, the redox-sensitive CPBA decorated co-assembled nano-micelles provided a promising strategy for tumor active targeting and redox-controlled intracellular synergistic combinational delivery of chemotherapeutics.

Camptothecin prodrug nanomicelle based on a boronate ester-linked diblock copolymer as the carrier of doxorubicin with enhanced cellular uptake.

A novel pH-sensitive polymeric prodrug of camptothecin (CPT) by polymerizing γ-camptothecin-glutamate N-carboxyanhydride (Glu (CPT)-NCA) on boronate ester-linked poly (ethyleneglycol) (PEG) directly via the amine-initiated ring open polymerization (ROP) has been developed. The resulting amphiphilic prodrug (mPEG-BC-PGluCPT) could self-assemble into nanoparticles and encapsulate doxorubicin (Dox) simultaneously in aqueous solution for dual-drug delivery. The formation of polymeric prodrug micelles (mPEG-BC@PGluCPT) was confirmed by the measurements of critical aggregation concentration (CAC), particle size, and morphology observations. The mPEG-BC@PGluCPT micelles were colloidally stable in solutions for two weeks. Polymeric prodrug micelles mPEG-BC@PGluCPT and Dox-loaded micelles mPEG-BC@PGluCPT⋅Dox showed sustained drug release profiles over 48 h. As expected, drug release was accelerated by the decreasement of pH value from 7.4 to 6.0, which demonstrated pH-dependent manner of drug release. Additionally, it was found that cellular uptake of mPEG-BC@PGluCPT⋅Dox micelles on HepG2 cells was higher than that on HL-7702 cells, especially in culture medium at pH 6.0. The enhanced cellular uptake of mPEG-BC@PGluCPT⋅Dox micelles under acidic condition on HepG2 cells resulted in the higher cytotoxicity of mPEG-BC@PGluCPT⋅Dox micelles at acidic pH than that at pH 7.4.

Rod-like cellulose nanocrystal/cis-aconityl-doxorubicin prodrug: A fluorescence-visible drug delivery system with enhanced cellular uptake and intracellular drug controlled release.

Rod-like nanomedicines facilitate cellular uptake. This research is aimed to develop fluorescence-visible rod-like nanomedicines with enhanced cellular uptake and intracellular drug controlled release based on cis-aconityl-doxorubicin (CAD) labeled cellulose nanocrystal rods (CNR). Particularly, CAD was synthesized by the ring-opening reaction between cis-aconitic anhydride (CAA) and the amino group of Doxorubicin (DOX). Amidation reaction occurred between the 6-carboxylic groups of CAD and the amino groups of aminated CNR to give CAD labeled CNR (CAD@CNR). Compared with CNR, CAD@CNR showed similar morphology and crystal structure. The mean length of CAD@CNR was ca. 118 nm with aspect ratio ranging from 12 to 15, facilitating their endocytosis. CAD@CNR prodrug was rather stable in pH 7.4 phosphate buffer solution but tended to be hydrolyzed to release DOX under acidic condition, due to the rapid degradation of amide bonds between DOX and cis-aconitic acid via an intramolecular acid-catalyzed mechanism. CAD@CNR prodrug showed sustained drug release profiles over 40 h, and the cumulative drug release showed a tendency to increase from 36 to 80% with the pH value decreasing from 7.4 to 5.0. The half maximal inhibitory concentration (IC50) of CAD@CNR prodrug against NCI H 460 cells without NH4Cl (lysosomotropic weak bases) pretreatment was 1.75 times higher than that with 40 mM NH4Cl pretreatment, further confirmed that the DOX release from the CAD@CNR prodrug was triggered by the low pH value of lysosome (pH 5.0). Compared with DOX·HCl, CAD@CNR prodrug showed enhanced cellular uptake ability during 12 or 24 h of incubation due to the endocytosis mechanism of CAD@CNR prodrug. After incubation with cells, CAD@CNR prodrug could be observed by using fluorescence microscope due to the red fluorescence of DOX. In a word, CAD@CNR showed great potential as fluorescence-visible drug delivery system with enhanced cellular uptake and intracellular drug release due to its rod-like morphology, suitable aspect ratio, and acid-triggered drug release.