Triple-Mechanism Enhanced Flexible SiO2 Nanofiber Composite Hydrogel with High Stiffness and Toughness for Cartilaginous Ligaments.

Hydrogels are widely used in tissue engineering, soft robotics and wearable electronics. However, it is difficult to achieve both the required toughness and stiffness, which severely hampers their application as load-bearing materials. This study presents a strategy to develop a hard and tough composite hydrogel. Herein, flexible SiO2 nanofibers (SNF) are dispersed homogeneously in a polyvinyl alcohol (PVA) matrix using the synergistic effect of freeze-drying and annealing through the phase separation, the modulation of macromolecular chain movement and the promotion of macromolecular crystallization. When the stress is applied, the strong molecular interaction between PVA and SNF effectively disperses the load damage to the substrate. Freeze-dried and annealed-flexible SiO2 nanofibers/polyvinyl alcohol (FDA-SNF/PVA) reaches a preferred balance between enhanced stiffness (13.71 ± 0.28 MPa) and toughness (9.9 ± 0.4 MJ m-3). Besides, FDA-SNF/PVA hydrogel has a high tensile strength of 7.84 ± 0.10 MPa, super elasticity (no plastic deformation under 100 cycles of stretching), fast deformation recovery ability and excellent mechanical properties that are superior to the other tough PVA hydrogels, providing an effective way to optimize the mechanical properties of hydrogels for potential applications in artificial tendons and ligaments.

A Comparative Study of the Effects of Electronic Cigarette and Traditional Cigarette on the Pulmonary Functions of C57BL/6 Male Mice.

INTRODUCTION: Electronic cigarettes (E-cigs) are in a controversial state. Although E-cig aerosol generally contains fewer harmful substances than smoke from burned traditional cigarettes, aerosol along with other compounds of the E-cigs may also affect lung functions and promote the development of lung-related diseases. We investigated the effects of E-cig on the pulmonary functions of male C57BL/6 mice and reveal the potential underlying mechanisms. METHODS: A total of 60 male C57BL/6 mice were randomly divided into four groups. They were exposed to fresh-air, traditional cigarette smoke, E-cig vapor with 12 mg/mL of nicotine, and E-cig with no nicotine for 8 weeks. Lung functions were evaluated by using quantitative analysis of the whole body plethysmograph, FlexiVent system, lung tissue histological and morphometric analysis, and RT-PCR analysis of mRNA expression of inflammation-related genes. In addition, the effects of nicotine and acrolein on the survival rate and DNA damage were investigated using cultured human alveolar basal epithelial cells. RESULTS: Exposure to E-cig vapor led to significant changes in lung functions and structures including the rupture of the alveolar cavity and enlarged alveolar space. The pathological changes were also accompanied by increased expression of interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: The findings of the present study indicate that the safety of E-cig should be further evaluated. IMPLICATIONS: Some people currently believe that using nicotine-free E-cigs is a safe way to smoke. However, our research shows that E-cigs can cause lung damage regardless of whether they contain nicotine.

Preparation of zeolitic imidazolate framework-67/wool fabric and its adsorption capacity for reactive dyes.

Zeolitic imidazolate framework-67 (ZIF-67) formed by Co2+ and 2-methylimidazole (MIM) is widely used for adsorption and separation of pollutants. However, there are some disadvantages for ZIF-67 powder, such as strong electrostatic interaction and difficulty in recovery from the liquid phase. The available way to solve the above problems is choosing a suitable substrate to load ZIF-67. The amino and hydroxyl of wool fabrics effectively capture and fix ZIF-67, making it easy to separate ZIF-67 by taking out the composite materials from aqueous solution. In this study, ZIF-67/Wool fabric (ZW) was successfully prepared. The results show that ZIF-67 has better adsorption performance for reactive dyes with more sulfonic groups, higher molecular weight and lower steric resistance. The equilibrium adsorption capacity of ZW for reactive red 195 was 4.15 mg g-1. The adsorption accorded with pseudo-second-order kinetic model and Langmuir isotherm. This study improved the application of ZIF-67, which provided a treatment method for dyeing wastewater and made it possible to recycle waste wool.

"Two-Step" Raman Imaging Technique To Guide Chemo-Photothermal Cancer Therapy.

Graphene oxide-wrapped gold nanorods (GO@AuNRs) offer efficient drug delivery as well as NIR laser photothermal therapy (PTT) in vitro and in vivo. However, no real-time observation of drug release has been reported to better understand the synergy of chemotherapy and PTT. Herein, surface-enhance Raman spectroscopy (SERS) is employed to guide chemo-photothermal cancer therapy by a two-step mechanism. In the presence of GO as an internal standard, SERS signals of DOX (doxorubicin) loaded onto GO@AuNRs are found to be pH-responsive. Both DOX and GO show strong SERS signals before the DOX@GO@AuNRs are endocytic. However, when the DOX@GO@AuNRs enter acidic microenvironments such as endosomes and/or lysosomes, the DOX signals start decreasing while the GO signals remain the same. This plasmonic antenna could be used to identify the appropriate time to apply the PTT laser during chemo-photothermal therapy.

Recycling cellulases by pH-triggered adsorption-desorption during the enzymatic hydrolysis of lignocellulosic biomass.

Recycling of cellulases is an effective way to reduce the cost of enzymatic hydrolysis for the production of cellulosic ethanol. In this study, we examined the adsorption and desorption behaviors of cellulase at different pH values and temperatures. Furthermore, we developed a promising way to recover both free and bound cellulases by pH-triggered adsorption-desorption. The results show that acidic pH (e.g., pH 4.8) was found to favor adsorption, whereas alkaline pH (e.g., pH 10) and low temperature (4-37 °C) favored desorption. The adsorption of cellulases reached an equilibrium within 60 min at pH 4.8 and 25 °C, leading to approximately 50 % of the added cellulases bound to the substrate. By controlling the pH of eluent (citrate buffer, 25 °C), we were able to increase the desorption efficiency of bound cellulases from 15 % at pH 4.8 to 85 % at pH 10. To recover cellulases after enzymatic hydrolysis, we employed adsorption by fresh substrate and desorption at pH 10 to recover the free cellulases in supernatant and the bound cellulases in residue, respectively. The recycling performance (based on the glucose yield) of this simple strategy could reach near 80 %. Our results provided a simple, low-cost, and effective approach for cellulase recycling during the enzymatic hydrolysis of lignocellulosic biomass.

Novel multifunctional environmentally friendly degradable zeolitic imidazolate frameworks@poly (γ-glutamic acid) hydrogel with efficient dye adsorption function.

Recently, metal-organic frameworks (MOFs) have been widely developed due to the rich porosity, excellent framework structure and multifunctional nature. Meanwhile, a series of MOFs crystals and MOF-based composites have been emerged. However, the widespread applications of MOFs are hindered by challenges such as rigidity, fragility, solution instability, and processing difficulties. In this study, we addressed these limitations by employing an in-situ green growth approach to prepare a zeolitic imidazolate frameworks-8@poly (γ-glutamic acid) hydrogel (ZIF-8@γ-PGA) with hierarchical structures. This innovative method effectively resolves the inherent issues associated with MOFs. Furthermore, the ZIF-8@γ-PGA hydrogel is utilized for dye adsorption, demonstrating an impressive maximum adsorption capacity of 1130 ± 1 mg/g for methylene blue (MB). The adsorption behavior exhibits an excellent agreement with both the kinetic model and isotherm. Meanwhile, because the adsorbent raw materials are all green non-toxic materials, multiple applications of materials can also be realized. Significantly, the results of antibacterial experiments showed that the ZIF-8@γ-PGA hydrogel after in-situ growth of ZIF-8 had better antibacterial properties. Thus, the ZIF-8@γ-PGA hydrogel has great potential for development in wound dressings, sustained drug owing to its biocompatibility and antibacterial activity.

Improvement of biodegradation of PET microplastics with whole-cell biocatalyst by interface activation reinforcement.

Polyethylene terephthalate (PET) is an important basic polymer, which was used widely in variety of fields. Due to its high crystallinity, compact structure and strong surface hydrophobicity, PET has prominent resistance to biodegradation. In recent years, microplastics, especially polyethylene terephthalate (PET) microplastics, was considered as serious threaten to ecosystems. In this study, alkali-resistant bacteria were used as whole-cell catalysts to try to improve the biodegradation of PET microplastics by increasing the bio-interfacial activity of the polymer substrate. Surfactants were applicated to enhance interfacial activation of enzyme and PET interactions. And an integrated strategy was constructed based on alkali resistant bacteria to catalysis the hydrolysis of PET. The results showed that Tween 20 had the most obvious promoting effect among the four interfacial biocatalysts on biological-chemical combined hydrolysis of PET microplastics with whole-cell biocatalysts in alkaline environment. Obvious etching and fracture were observed on the PET fibre surface after biodegradation in presence of surfactant. The weight loss rate of PET substrate can reach 11.04% after 5 days of biodegradation. Thus, this research provides a promising method for efficient degradation of PET microplastics.

[RHD Gene Analysis of A Blood Donor with Del Phenotype].

OBJECTIVE: To analyze the RHD genotype of a blood donor with Del phenotype in Yunnan. METHODS: Rh serological phenotype was identified. RHD gene was detected by PCR-SSP typing, and its 10 exons were sequenced. Exon 9 was amplified for sequencing and analysis. RHD zygosity was detected. RESULTS: The Rh phenotype of this specimen was CcDelee. Genomic DNA exhibited a 1 003 bp deletion spanning from intron 8, across exon 9 into intron 9. The deletion breakpoints occurred between two 7-bp short tandem repeat sequences. There was no variation in the sequences of the remaining exons. The Rh hybridization box test showed that there was one RHD negative allele. CONCLUSION: This specimen is Del type caused by deletion of RHD exon 9.

Bio-based poly (γ-glutamic acid)-gelatin double-network hydrogel with high strength for wound healing.

Building bio-based hydrogels with high strength and biocompatibility is still a challenge. Herein, we successfully constructed a hybrid double-network (DN) full biological hydrogel with excellent mechanical properties and biocompatibility by introducing a physically cross-linked gelatin (GEL) network in a covalently cross-linked poly (γ-glutamic acid) (γ-PGA) network. The γ-PGA-GEL DN hydrogel demonstrated ultra-high compression performance (38 MPa), which was better than all currently reported γ-PGA-based hydrogels, and its tensile performance (0.27 MPa) was also satisfactory. Due to the unique multi-crosslinked DN structure, the γ-PGA-GEL DN hydrogel had better recovery and healing properties than those of the γ-PGA single-network (SN) hydrogel. In addition, the γ-PGA-GEL DN hydrogel exhibited good transparency, swelling and degradability. In vitro cell experiments demonstrated that the γ-PGA-GEL DN hydrogel was beneficial to cell adhesion and proliferation. The evaluation of the full-thickness skin defects model in rats exhibited that the γ-PGA-GEL DN hydrogel could significantly accelerate wound healing. These results indicated that the γ-PGA-GEL DN hydrogel was an ideal candidate material for wound dressing.

Washable Patches with Gold Nanowires/Textiles in Wearable Sensors for Health Monitoring.

Textile-based flexible electronic devices have attracted tremendous attention in wearable sensors due to their excellent skin affinity and conformability. However, the washing process of such devices may damage the electronic components. Here, a textile-based piezoresistive sensor with ultrahigh sensitivity was fabricated through the layered integration of gold nanowire (AuNW)-impregnated cotton fabric and silver ink screen-printed nylon fabric electrodes, sealing with Parafilm. The prepared piezoresistive sensing patch exhibits outstanding performance, including high sensitivity (914.970 kPa-1, <100 Pa), a fast response time (load: 38 ms, recovery: 34 ms), and a low detection limit (0.49 Pa). More importantly, it can maintain a stable signal output even after 30 000 s of loading-unloading cycles. Furthermore, this sensing patch can efficiently detect breathing, pulse, heart rate, and joint movements during the activities. After five cycles of mechanical washing, the piezoresistive performance keeps 90.3%, demonstrating the high feasibility of this sensor in practical applications. This sensor has a simple fabrication, with good fatigue resistance and durability due to its all-fabric core element. It provides a strategy to address the machine-washing issues in textile electronics. This washable textile sensor is expected to show significant potential in future applications of health monitoring, human-machine interfaces, and artificial skin.

A thread/fabric-based band as a flexible and wearable microfluidic device for sweat sensing and monitoring.

Flexible biosensors for monitoring systems have emerged as a promising portable diagnostics platform due to their potential for in situ point-of-care (POC) analytic devices. Assessment of biological analytes in sweat can provide essential information for human physiology. Conventional measurements rely on laboratory equipment. This work exploits an alternative approach for epidermal sweat sensing and detection through a wearable microfluidic thread/fabric-based analytical device (µTFAD). This µTFAD is a flexible and skin-mounted band that integrates hydrophilic dot-patterns with a hydrophobic surface via embroidering thread into fabric. After chromogenic reaction treatment, the thread-embroidered patterns serve as the detection zones for sweat transferred by the hydrophilic threads, enabling precise analysis of local sweat loss, pH and concentrations of chloride and glucose in sweat. Colorimetric reference markers embroidered surrounding the working dots provide accurate data readout either by apparent color comparison or by digital acquirement through smartphone-assisted calibration plots. On-body tests were conducted on five healthy volunteers. Detection results of pH, chloride and glucose in sweat from the volunteers were 5.0-6.0, 25-80 mM and 50-200 µM by apparent color comparison with reference markers through direct visual observation. Similar results of 5.47-6.30, 50-77 mM and 47-66 µM for pH, chloride and glucose were obtained through calibration plots based on the RGB values from the smartphone app Lanse®. The limit of detection (LOD) is 10 mM for chloride concentration, 4.0-9.0 for pH and 10 µM for glucose concentration, respectively. For local sweat loss, it is found that the forehead is the region of heavy sweat loss. Sweat secretion is a cumulating process with a lower sweat rate at the beginning which increases as body movement continues along with increased heat production. These results demonstrate the capability and availability of our sensing device for quantitative detection of multiple biomarkers in sweat, suggesting the great potential for development of feasible non-invasive biosensors, with a similar performance to conventional measurements.

Bio-based poly (γ-glutamic acid) hydrogels reinforced with bacterial cellulose nanofibers exhibiting superior mechanical properties and cytocompatibility.

Natural polymer hydrogels are expected to be promising biomaterial because of its excellent biocompatibility and biodegradability, but they are soft and easily broken. Herein, the poly (γ-glutamic acid) (γ-PGA)/bacterial cellulose (BC) composite hydrogels with excellent mechanical properties were constructed by introducing bacterial cellulose. The γ-PGA/BC composite hydrogels were obtained by the covalent cross-linking of γ-PGA in the BC nanofibers suspensions. The γ-PGA/BC composite hydrogels exhibited excellent strength and toughness due to the more effective energy dissipation of hydrogen bonds network among BC nanofibers and γ-PGA hydrogel matrix and BC also acts as an enhancer. The compressive fracture strength and toughness of the γ-PGA/BC composite hydrogels could reach up to 5.72 MPa and 0.42 MJ/m3 respectively. Additionally, the tensile strength of γ-PGA/BC composite hydrogels were improved 8.16 times compared with γ-PGA single network hydrogels. More significantly, BC could disperse evenly in the γ-PGA hydrogels because of the hydrophilic nature of γ-PGA and BC nanofillers, which led to good interface compatibility. The result of cytotoxicity tests indicated that γ-PGA/BC composite hydrogels present excellent cytocompatibility, which suggested that the γ-PGA/BC composite hydrogels could serve as promising materials for many biomaterial related applications.

A poly(allylamine hydrochloride)/poly(styrene sulfonate) microcapsule-coated cotton fabric for stimulus-responsive textiles.

This study reports the design of a stimulus-responsive fabric incorporating a combination of microcapsules, containing polyelectrolytes poly(allylamine hydrochloride) (PAH) and poly(styrene sulfonate) sodium salt (PSS), formed via a layer-by-layer (LBL) approach. The use of PAH and PSS ensured that the microcapsule structure was robust and pH-sensitive. SEM and TEM studies showed that the composite microcapsule (PAH/PSS) n PAH had a spherical morphology with a hollow structure. FTIR demonstrated the presence of PAH and PSS, confirming the composition of the microcapsule shell. DSC showed that the microcapsules were thermally stable. The size of the microcapsules ranged from 4 µm to 6 µm. The hollow microcapsules can be used as a carrier for loading and releasing chemicals under different pH conditions. The release rate of Rhodamine-B from (PAH/PSS) n PAH microcapsules was higher at pH 5.8 than that at 7.4, confirming the pH sensitivity. The hollow structure of (PAH/PSS) n PAH microcapsules is expected to act as a carrier and medium to introduce functional chemicals into the fabric with long-lasting property and pH stimulus responsivity. Furthermore, a positively charged compound with ethylene oxide groups was added during the coating process as a crosslinker binding (PAH/PSS)2PAH for the microcapsules with the cotton fabric more efficiently. Using this method, numerous substances, e.g., drugs, dyes, natural herbs, or perfumes, could be stored into the LBL microcapsules for a relatively long time, constantly releasing them from the coated textiles. Since LBL microcapsules were easy to combine with fabrics, this study provided a feasible approach for the preparation of functional stimulus-responsive textiles.

Bio-Preparation and Regulation of Pyrrole Structure Nano-Pigment Based on Biomimetic Membrane.

Microbial pigments, regarded as the most potential biomass pigments, have lately attracted increasing attention in textile dyeing due to their sustainability and cleaner production. The pyrrole structure microbial pigment, called prodigiosin, recently have become a research hotspot for its bright colors and antibacterial function. However, in most case the extraction and preparation are time-consuming and expensive processes since these kinds of microbial pigments are intracellular metabolites. In order to promote the application of microbial pigments in textile dyeing, a novel idea of preparing dye liquid of pyrrole structure pigments based on fermentation broth was put forward via increasing the proportion of extracellular pigments. A model membrane platform was established with a planar lipid bilayer to investigate transmembrane transport of microbial pigments and permeability barrier of cell membrane. The nano-dispersion of pigments was produced as the dye liquor owing to high-throughput transmembrane transfer of intracellular pigments and the increase of extracellular pigments proportion. The results indicated that the size and surface electrical properties of the pigments had contributed much to the mass transfer. It is also showed that transmembrane transmission of the intracellular pigments could be regulated by physical and chemical methods. With the improvement of transmembrane transfer efficiency of microbial pigments and the proportion of extracellular pigments, the complicated biological separation process could be avoided and the application of microbial pigments in textile dyeing can be promoted.

Design and Optimization of Flexible Polypyrrole/Bacterial Cellulose Conductive Nanocomposites Using Response Surface Methodology.

Flexible conductive materials have greatly promoted the rapid development of intelligent and wearable textiles. This article reports the design of flexible polypyrrole/bacterial cellulose (PPy/BC) conductive nanocomposites by in situ chemical polymerization. Box-Behnken response surface methodology has been applied to optimize the process. The effects of the pyrrole amount, the molar ratio of HCl to pyrrole and polymerization time on conductivity were investigated. A flexible PPy/BC nanocomposite was obtained with an outstanding electrical conductivity as high as 7.34 S cm-1. Morphological, thermal stability and electrochemical properties of the nanocomposite were also studied. The flexible PPy/BC composite with a core-sheath structure exhibited higher thermal stability than pure cellulose, possessed a high areal capacitance of 1001.26 mF cm-2 at the discharge current density of 1 mA cm-2, but its cycling stability could be further improved. The findings of this research demonstrate that the response surface methodology is one of the most effective approaches for optimizing the conditions of synthesis. It also indicates that the PPy/BC composite is a promising material for applications in intelligent and wearable textiles.

Effective gene delivery of shBMP-9 using polyethyleneimine-based core-shell nanoparticles in an animal model of insulin resistance.

Bone morphogenetic protein (BMP)-9 has been associated with insulin resistance and type 2 diabetes mellitus. However, methods for delivering exogenous BMP-9 genes in vivo are lacking. In this study, we developed a gene delivery system using polyethyleneimine (PEI)-based core-shell nanoparticles (PCNs) as gene delivery carriers, and investigated the effectiveness and safety for delivery of the shBMP-9 gene. PCNs possessed a well-defined core-shell nanostructure with hydrophobic polymer cores and dense PEI shells of uniform particle size and highly positively charged surfaces. In vitro evaluation suggested that PCNs had high loading capacity for exogenous genes and low cytotoxicity toward hepatocytes. The transfection efficiency of PCNs/pENTR-shBMP9 complexes was higher than that of commercial lipofectamine 2000/shBMP9. In vivo studies showed that PCNs/pENTR-shBMP9 transfection led to a significant decrease in hepatic BMP9 expression compared with pENTR-shBMP9 transfection. Under high fat diet (HFD) feeding, PCNs/pENTR-shBMP9 mice exhibited aggravated glucose and insulin tolerance. At a molecular level, PCNs/pENTR-shBMP9 mice displayed elevated PEPCK protein levels and lower levels of InsR and Akt phosphorylation than pENTR-shBMP9 mice. These results suggest that the biological effects of PCNs/pENTR-shBMP9 in vivo are much more effective than those of pENTR-shBMP9. Therefore, the polyethyleneimine (PEI)-based core-shell nanoparticle can be applied as promising nanocarriers for effective and safe gene delivery.

Biodegradation of Microplastic Derived from Poly(ethylene terephthalate) with Bacterial Whole-Cell Biocatalysts.

At present, the pollution of microplastic directly threatens ecology, food safety and even human health. Polyethylene terephthalate (PET) is one of the most common of microplastics. In this study, the micro-size PET particles were employed as analog of microplastic. The engineered strain, which can growth with PET as sole carbon source, was used as biocatalyst for biodegradation of PET particles. A combinatorial processing based on whole-cell biocatalysts was constructed for biodegradation of PET. Compared with enzymes, the products can be used by strain growth and do not accumulated in culture solution. Thus, feedback inhibition of products can be avoided. When PET was treated with the alkaline strain under high pH conditions, the product concentration was higher and the size of PET particles decreased dramatically than that of the biocatalyst under neutral conditions. This shows that the method of combined processing of alkali and organisms is more efficient for biodegradation of PET. The novel approach of combinatorial processing of PET based on whole-cell biocatalysis provides an attractive avenue for the biodegradation of micplastics.

In situ degradation kinetics of 6 roughages and the intestinal digestibility of the rumen undegradable protein.

Three ruminally fistulated Xuanhan steers weighting 312.5 (±23.85) kg were used to determine the kinetics of ruminal degradation of nutrients using in situ nylon bag technique, and a modified 3-step in vitro procedure was adopted to estimate intestinal digestibility of 16-h rumen undegradable protein (RUP) of maize cob (MC), distillers grains (DG), spent mushroom substrate (SMS), starch residue of sweet potato (SRSP), citrus pulp (CPP), and rice straw (RS). Samples were incubated for 0, 2, 6, 16, 24, 36, 48 and 72 h. Additional samples were incubated for 16 h in the rumen, and the residues from these bags were transferred to the nitrogen-free polyester bags for determination of intestinal digestibility in vitro. The highest DM disappearance at 6-h incubation was in SRSP (P < 0.01), and that at 36, 48, and 72 h was in CPP (P < 0.01). The lowest DM disappearance at 2- and 6-h incubation was in RS and SMS (P < 0.01), and that at 36, 48, and 72 h incubation was in RS, MC, and DG (P < 0.01). The lowest and greatest CP disappearance was in RS and DG, respectively, at all the incubation times (P < 0.01). There was no difference (P > 0.07) on CP disappearance between DG and MC at all the time points except for 16 and 24 h. NDF and ADF disappearance for SRSP was significantly higher (P < 0.01) than other roughages at all the time points except for ADF at 72 h. The lowest NDF and ADF disappearance was in DG at all the time points (P < 0.01) except 2 and 6 h. The effective degradability (ED) of DM was the highest in CPP (P < 0.01) and the lowest in MC and RS (P < 0.01). The highest and lowest ED of CP was in DG and in RS (P < 0.01), respectively. The ED of NDF was the highest in SRSP (P < 0.01), followed by CPP and RS, and the lowest in DG (P < 0.01). The ED of ADF was the highest in SRSP and CPP (P < 0.05), and the lowest in DG (P < 0.01). For MC, DG SMS, SRSP, CPP, and RS, the intestinal digestibility of RUP was 95.28%, 37.23%, 38.72%, 48.06%, 54.49%, and 37.88%, respectively, and the content of intestinal digestible crude protein (IDCP) was 23.65, 83.63, 35.63, 15.03, 25.60, and 12.03 g/kg, respectively. Distillers grain was considered to be of good quality for the greatest content of IDCP. Although not readily degraded in rumen, CP in MC may be digested well in small intestine.

Hybrid Iron Oxide-Graphene Oxide-Polysaccharides Microcapsule: A Micro-Matryoshka for On-Demand Drug Release and Antitumor Therapy In Vivo.

Premature drug release is a common drawback in stimuli-responsive drug delivery systems (DDS), especially if it depends on internal triggers, which are hard to control, or a single external stimulus, which can only have one function. Thus, many DDS systems have been reported that combined different triggers; however, limited success has been established in fine-tuning the release process, mainly due to the poor bioavailability and complexity of the reported designs. This paper reports the design of a hybrid microcapsule (h-MC) by a simple layer-by-layer technique comprising polysaccharides (sodium alginate, chitosan, and hyaluronic acid), iron oxide, and graphene oxide (GO). Electrostatic assembly of the oppositely charged polysaccharides and graphene sheets provided a robust structure in which to load drugs through pH control. The polysaccharide component ensured high biocompatibility, bioavailability, and tumor cells targeting. The alternative magnetic field and near-infrared laser triggerable Fe3O4@GO component provided for dual high-energy and high-penetration hyperthermia therapy. On-demand drug release from h-MC can be achieved by synchronizing these external triggers, making the release highly controllable. The synergistic effect of hyperthermia and chemotherapy was successfully confirmed in vitro and in vivo.