Dual Stimuli-responsiveness Research Articles

Hybrid Gold Nanorod-Based Nanoplatform with Chemo and Photothermal Activities for Bimodal Cancer Therapy.

Metal nanoparticles (NPs), particularly gold nanorods (AuNRs), appear as excellent platforms not only to transport and deliver bioactive cargoes but also to provide additional therapeutic responses for diseased cells and tissues and/or to complement the action of the carried molecules. In this manner, here, we optimized a previous developed metal-based nanoplatform composed of an AuNR core surrounded by a polymeric shell constructed by means of the layer-by-layer approach, and in which very large amounts of the antineoplasic drug doxorubicin (DOXO) in a single loading step and targeting capability thanks to an outer hyaluronic acid layer were incorporated by means of an optimized fabrication process (PSS/DOXO/PLL/HA-coated AuNRs). The platform retained its nanometer size with a negative surface charge and was colloidally stable in a range of physiological conditions, in which only in some of them some particle clustering was noted with no precipitation. In addition, the dual stimuli-responsiveness of the designed nanoplatform to both endogenous proteases and external applied light stimuli allows to perfectly manipulate the chemodrug release rates and profiles to achieve suitable pharmacodynamics. It was observed that the inherent active targeting abilities of the nanoplatfom allow the achievement of specific cell toxicity in tumoral cervical HeLa cells, whilst healthy ones such as 3T3-Balb fibroblast remain safe and alive in agreement with the detected levels of internalization in each cell line. In addition, the bimodal action of simultaneous chemo- and photothermal bioactivity provided by the platform largely enhances the therapeutic outcomes. Finally, it was observed that our PSS/DOXO/PLL/HA-coated AuNRs induced cell mortality mainly through apoptosis in HeLa cells even in the presence of NIR light irradiation, which agrees with the idea of the chemo-activity of DOXO predominating over the photothermal effect to induce cell death, favoring an apoptotic pathway over necrosis for cell death.

3D-printed in-line and out-of-plane layers with stimuli-responsive intelligence

Smart materials and structures with shape memory properties have recently gained attention due to their unique ability to remember their original shape, dimensional flexibility, structural programmability, and multi-material compatibilities. They have found applications in morphing structures, heat storage, flexible electronics, soft/micro-robotics, metamaterials, biomedical scaffolds, and space missions. Most applications of these systems require multifunctionality with high precision controls over multi-materials. However, most current manufacturing cannot process disparate materials without generating phase separation or structural instabilities. This research presents a new 3D printing process via the Multiphase Direct Ink Writing (MDIW) mechanism to produce in-line and out-of-plane microlayers. The selective deposition of polyether-thermoplastic polyurethane (TPU)/polycaprolactone (PCL) and polyester-TPU/iron oxide (Fe3O4) is investigated for thermal and magnetic dual stimuli-responsiveness. During the MDIW manufacturing, specific sublayers within each printing line for optimized domain size are produced with the stacking of the layers along the z-axis to investigate their influences on the stimuli-responsiveness. The mechanical, thermal, and thermomechanical characterizations can reveal the time-temperature-dimension relationships in different media (i.e., air and water) showing a precisely controlled actuation phenomenon and shedding light on their broad applications in defense, energy, health, and sustainability.

Enzyme and Thermo Dual-stimuli Responsive DOX Carrier Based on PNIPAM Conjugated Mesoporous Silica.

Stimuli-responsive drug delivery systems have been proven to be a promising strategy to enhance tumor localization, overcome multidrug resistance (MDR), and reduce the side effects of chemotherapy agents. In this study, a temperature and redox dual stimuli-responsive system using mesoporous silica nanoparticles (MSNs) for targeted delivery of doxorubicin (DOX) was developed. Mesoporous silica nanoparticles were capped with poly(N-isopropylacrylamide) (PNIPAM), a thermo-sensitive polymer, with atom transfer radical polymerization (ATRP) method, via disulfide bonds (DOX-MSN-S-S-PNIPAM) to attain a controlled system that releases DOX under glutathione-rich (GSH-rich) environments and temperatures above PNIPAM's lower critical solution temperature (LCST). Morphological and physicochemical properties of the nanoparticles were indicated using transmission electron microscopy (TEM), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and Brunauer-Emmett-Teller (BET). The drug release tests were performed at 25°C and 41°C in the absence and presence of the DTT, and the obtained results confirmed the synergic effect of temperature and reductive agent on a dual responsive release profile with a 73% cumulative release at 41°C and reductive environment during 240 min. The average loaded drug content and encapsulation efficacy were reported as 42% and 29.5% at the drug: nanoparticle ratio of 1.5: 1. In vitro cytotoxicity assays on MCF-7 cell lines indicated significant viability decreased in cells exposed to DOX-MSN-S-S-PNIPAM compared to the free drug (DOX). Based on the results, DOX-MSN-S-S-PNIPAM has shown much more efficiency with stimuli-responsive properties in comparison to DOX on MCF-7 cancer cell lines.

Programmable Drug Release from a Dual-Stimuli Responsive Magnetic Metal–Organic Framework

Along with the increasing incidence of cancer and drawbacks of traditional drug delivery systems (DDSs), developing novel nanocarriers for sustained targeted-drug release has become urgent. In this regard, metal–organic frameworks (MOFs) have emerged as potential candidates due to their structural flexibility, defined porosity, lower toxicity, and biodegradability. Herein, a FeMn-based ferromagnetic MOF was synthesized from a preassembled Fe2Mn(μ3-O) cluster. The introduction of the Mn provided the ferromagnetic character to FeMn-MIL-88B. 5-Fluoruracil (5-FU) was encapsulated as a model drug in the MOFs, and its pH and H2S dual-stimuli responsive controlled release was realized. FeMn-MIL-88B presented a higher 5-FU loading capacity of 43.8 wt % and rapid drug release behavior in a tumor microenvironment (TME) simulated medium. The carriers can rapidly release loaded drug of 70% and 26% in PBS solution (pH = 5.4) and NaHS solution (500 μM) within 24 h. The application of mathematical release models indicated 5-FU release from carriers can be precisely fitted to the first-order, second-order, and Higuchi models of release. Moreover, the cytotoxicity profile of the carrier against human embryonic kidney cells (HEK293T) suggests no adverse effects up to 100 μg/mL. The lesser toxic effect on cell viability can be attributed to the low toxicity values [LD50 (Fe) = 30 g·kg–1, (Mn) = 1.5 g·kg–1, and (terephthalic acid) = 5 g·kg–1] of the MOFs structural components. Together with dual-stimuli responsiveness, ferromagnetic nature, and low toxicity, FeMn-MIL-88B MOFs can emerge as promising carriers for drug delivery applications.

Using carbonized hybrid FeNPs@ZIF-8 for the sustained release of doxorubicin hydrochloride

Controlling the slow release of drugs in carriers and reducing environmental pollution and damage from antibiotics is important and challenging research. In this paper, a novel composite material of carbonized FeNPs@ZIF-8 (C-Fe3O4 @ZIF-8) was used to load and release doxorubicin hydrochloride (DOX). Compared with conventional ZIFs materials, greatly enhancing the magnetic properties, drug loading capacity and controlled drug release of the carrier agent. Interestingly, by establishing a dual stimulus response system with environmental factors of pH and temperature, results showed release rate of 61.6 % at a pH of 3 and a temperature of 37 °C. In addition, the SEM-EDS results showed that the surface of C-Fe3O4 @ZIF-8 was partially broken but maintained a stable morphology before and after release. Meanwhile the nitrogen absorption desorption curve (BET) and hysteresis loop reveal that C-Fe3O4 @ZIF-8 can maintain a large specific surface area and a magnetization intensity of 12.4 emu g−1 after release. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR), on the other hand, reveal the presence of partial ligand and hydrogen bond breaks during the release of DOX from DOX-loaded C-Fe3O4 @ZIF-8. Finally, the release of DOX from C-Fe3O4 @ZIF-8 at different pH and temperature is consistent with the Higuch and Bhaskas models, where the latter dominates and proposes a release mechanism. Therefore, the magnetic composite C-Fe3O4 @ZIF-8 in this study has great potential for DOX to effectively control drug release and targeted cancer therapy.

Smart ionic liquid/water mixture system with dual stimuli-response to temperature and CO2

Smart ionic liquid/water mixture system with dual stimuli-response to temperature and CO2

A multi-hit therapeutic nanoplatform for hepatocellular carcinoma: Dual stimuli-responsive drug release, dual-modal imaging, and in situ oxygen supply to enhance synergistic therapy.

Nanomedicine has been widely studied for the diagnosis and treatment of hepatocellular carcinoma (HCC). How to synthesize a nanoplatform possessing a high synergistic therapeutic efficacy remains a challenge in this emerging research field. In this study, a convenient all-in-one therapeutic nanoplatform (FTY720@AM/T7-TL) is designed for HCC. This advanced nanoplatform consists of multiple functional elements, including gold-manganese dioxide nanoparticles (AM), tetraphenylethylene (T), fingolimod (FTY720), hybrid-liposome (L), and T7 peptides (T7). The nanoplatform is negatively charged at physiological pH and can transit to a positively charged state once moving to acidic pH environments. The specially designed pH-responsive charge-reversal nanocarrier prolongs the half-life of nanodrugs in blood and improves cellular uptake efficiency. The platform achieves a sustained and controllable drug release through dual stimulus-response, with pH as the endogenous stimulus and near-infrared as the exogenous stimulus. Furthermore, the nanoplatform realizes in situ O2 generation by catalyzing tumor over-expressed H2O2, which alleviates tumor microenvironment hypoxia and improves photodynamic therapy. Both in vitro and in vivo studies show the prepared nanoplatform has good photothermal conversion, cellular uptake efficiency, fluorescence/magnetic resonance imaging capabilities, and synergistic anti-tumor effects. These results suggest that the prepared all-in-one nanoplatform has great potential for dual-modal imaging-guided synergistic therapy of HCC.

Preparation and characterization of novel functional tri-block copolymer for constructing temperature/redox dual-stimuli responsive micelles

Herein, we reported a novel tri-block copolymer synthesized by segmented ring-opening polymerization of temperature-sensitive 5-(pyrrolidine-1-carbonyl) oxepan-2-one monomer (VPyCL) and redox-sensitive macrocyclic disulfide-substituted carbonate monomer (MSS). The structure of the copolymers was confirmed by GPC, 1H NMR and 13C NMR. The obtained tri-block copolymers could self-assemble in aqueous solution to form well-structured micelles, with the mPEG-b-PVPyCL block acting as the hydrophilic coronal and the PSS block acting as the hydrophobic core. Dynamic light scattering (DLS) studies confirmed that micelles formed by these tri-block copolymers with different block ratios could respond to different temperature ranges during the heating/cooling process and respond to reducing agent glutathione (GSH). In addition, transmission electron microscopy (TEM) results further confirmed the polymeric micelles’ dual-stimuli responsiveness. The potential application of this type of dual-stimuli responsive micelles in drug delivery systems was evaluated using doxorubicin (DOX) as the model molecule. The stimulus-dependent responsive behaviors of obtained micelles can be applied to the construction of smart materials capable of performing multiple functions under the appropriate conditions.

Multi-stimuli responsive amphiphilic diblock copolymers by a combination of ionic liquid-mediated cationic polymerization and recyclable alloy nanoparticle-mediated photoRDRP

Poly(alkyl vinyl ether)-containing multifunctional block copolymers (BCPs) are challenging to synthesize and still limited in numbers despite their possible applications in high-tech areas. This article presents the synthesis of unprecedented amphiphilic poly(2-thioethyl vinyl ether)-block-poly(poly(ethylene glycol) methacrylate) (PTEVE-b-PPEGMA) BCPs via sequential ionic liquid-mediated cationic polymerization of CEVE and recyclable alloy-mediated photoRDRP of PEGMA, followed by post-polymerization modification of the pendant -CH2CH2Cl functionality to -CH2CH2SH. Controlled nature of both the cationic polymerization and photoRDRP was demonstrated by the first-order kinetic and linear increase of molecular weight with increase of monomer conversion, keeping low dispersity values. The synthesized PTEVE-b-PPEGMA BCP exhibited a dual (redox and temperature) stimuli-response. The cloud point of PTEVE-b-PPEGMA BCP can be tuned by changing the PEGMA mol% in the BCP. Amphiphilic PTEVE-b-PPEGMA diblock copolymer undergoes self-aggregation forming spherical nano-objects. These promising PTEVE-b-PPEGMA diblock copolymers could be used for many applications, including dual stimuli-responsive materials, materials with tunable hydrophobicity, and contaminant removal.

Dual stimulus response mechanical properties tunable biodegradable and biocompatible PLCL/PPDO based shape memory composites

The aliphatic polyester poly(L-lactide-co-ε-caprolactone)(PLCL) was synthesized successfully in this research. And a temperature-responsive and water-responsive shape memory composite was prepared by the physical blend of PLCL and poly (p-dioxanone) (PPDO) for the first time. The thermal properties, crystallinity, microstructure, mechanical properties, shape memory behavior, and degradation properties of PLCL/PPDO composites were comprehensively investigated. The results showed that the mechanical properties of the composite could be adjusted with the addition ratio of PPDO. All materials possessed excellent shape memory fixation rates: close to 100%. PPDO improved the shape memory recovery ratio of PLCL without affecting the shape memory fixation ratio of PLCL. PL/PP82 showed the best shape memory recovery ratio at 37°C with 91.34 ± 3.56%. A combination of in situ wide-angle X-ray scattering and tensile modes was used to elucidate the unique mechanism of shape memory in the air for this range of composites. PL/PP82 also exhibited excellent thermal and water-induced shape memory effects in water at 37 °C, with a rapid return to the original state of the composite within 19 s. The introduction of PPDO improved the degradation rate of the composite and regulated the rate of degradation. Additionally, the addition of PPDO significantly enhanced the hydrophilicity of the composites, which promoted proliferative adhesion of osteoblasts to the composite surface. Thus, the temperature and water responsive shape memory composites had great potential in bone tissue engineering applications.

PVA/gelatin/β-CD-based rapid self-healing supramolecular dual-network conductive hydrogel as bidirectional strain sensor

Hydrogel-based flexible sensors have exhibited great application prospect in the fields of e-skin, movement monitoring and human-computer interaction. Nevertheless, it is still a difficult problem to construct the biomass-based hydrogel sensors with considerable mechanical property, biocompatibility, self-healing property, sensitivity, self-adhesion and fatigue resistance. Herein, a gelatin-based dual-network (DN) hydrogel sensor with multiple dynamic crosslinking was successfully fabricated, in which the dynamic Schiff base bonds between gelatin and an aldehyde-containing supramolecular crosslinker (PCD-Fc-CHO) formed by the host-guest complexing of β-cyclodextrin (β-CD) to ferrocene (Fc) were used to construct the first network of the hydrogel, while the reversible borate ester bonds of PVA with borax were utilized to establish the second network. Meantime, carbon nanotubes (CNTs) were added to endow the gelatin-based DN hydrogel with good conductivity and improved mechanical property. The prepared gelatin-based DN hydrogel possesses favorable ductility (1200%), biocompatibility, double self-healing (HE = 96%), high sensitivity (GF = 6.4), self-adhesion (repeatable adhesion), dual stimuli-responsiveness (pH and oxidation), plasticity and fatigue resistance. The DN hydrogel-based strain sensor can not only monitor various human body (e.g. fingers, knees, speech, etc.) movements and vital signs (pulse), but also monitor in vitro the breathing movements of pig lungs. Interestingly, the self-healed gelatin-based DN hydrogel sensor can also be reused, and its monitoring ability is basically the same as the original hydrogel. This work puts forward a new strategy for the construction of multiple dynamically cross-linked biomass-based self-healing hydrogels as multifunctional wearable flexible sensors.

Dual stimuli-responsive dendronized prodrug derived from poly(oligo-(ethylene glycol) methacrylate)-based copolymers for enhanced anti-cancer therapeutic effect

In this study, we developed an enzyme- and pH-responsive dendronized poly(oligo-(ethylene glycol) methacrylate) (pOEGMA)-doxorubicin (DOX) polymeric prodrug, which combined the pOEGMA structure with a degradable peptide dendron. The introduction of the dendron in the prodrug hindered the entanglement of brush oligo-(ethylene glycol) (OEG) chains, allowed the prodrug to possess dual stimuli-responsiveness, and mediated self-assembly of the polymeric prodrug to form stable nanoparticles (NPs). Brush conformation of polyethylene glycol (PEG) side chains endowed the NPs with long-term circulation with a half-life of 16.0 h. The dual-responsive dendritic structure enhanced cellular uptake of NPs and facilitated drug release in response to overexpressed cathepsin B and an acidic pH in the tumor microenvironment, resulting in an enhanced therapeutic effect with a tumor inhibition rate of 72.9% for 4T1 tumor-bearing mice. The NPs were demonstrated to possess great hemocompatibility and biosafety. Therefore, this strategy could provide great insight for the design of poly(oligo-(ethylene glycol) methacrylate)-based copolymers as drug delivery carriers. Statement of significanceWe propose a dual-stimuli-responsive dendronized strategy for improving the cancer therapeutic effect of the poly(oligo-(ethylene glycol) methacrylate) (pOEGMA)-based drug conjugates. The introduction of the functional dendron promotes self-assembly of the polymeric prodrug into nanoparticles, hindering the entanglement of brush oligo-(ethylene glycol) (OEG) chains in the conjugated drugs. The obtained poly OEGMA-GFLG-Dendron-NH-N=DOX nanoparticles maintains long circulation, while addresses the drug release issue due to the presence of high-density PEG. The drug delivery system exhibits a high therapeutic potentcy with negligible side effects.

Dual-responsive drug release and fluorescence imaging based on disulfide-pillar[4]arene aggregate in cancer cells

The construction of multistimuli-responsive nanoaggregate has become one of the increasingly significant research topics in supramolecular chemistry. We herein reported the pH- and glutathione dual-responsive supramolecular assemblies fabricated by the disulfide-containing pillar[4]arene and tetraphenylethylene derivatives possessing different alkyl chains in length. Morphological characterization experiments showed the binary supramolecular assemblies formed well-defined nanoparticles, which could facilitate their endocytosis in cells. More remarkably, due to the compact nanostructures and the existence of acidifiable carboxyl group and bioreducible disulfide linkage in pillar[4]arene, the obtained nanoaggregates presented high drug-loading efficiency and sustained drug release behaviors, as well as the targeted fluorescence imaging ability in cancer cells. Thus, it can be envisioned that such microenvironment-adaptable supramolecular nanoassemblies featuring dual stimuli-responsiveness and fluorescence-imaging abilities may be developed as more appealing nanosystems for the therapy of refractory disease.

An UV-photo and ionic dual responsive interpenetrating network hydrogel with shape memory and self-healing properties.

Shape memory hydrogels have attracted extensive attention in fields such as artificial tissues, biomimetic devices and diagnostics, and intelligent biosensors. However, the practical applications were hindered by the absence of self-healing capability and multi-stimuli-responsiveness. To address these issues, we developed a shape memory hydrogel with self-healing and dual stimuli-response performance. The hydrogel system was constructed via an interpenetrating network consisting of in situ radical polymerization and host–guest interaction. The hydrogel exhibited rapid self-healing property, which can be stretched after self-healing for 1 min at 25 °C. Besides, the hydrogel displayed varied swelling performance in different light or solvent conditions. Moreover, the hydrogel showed a dual stimuli-responsive shape memory effect to ultraviolet (UV) light and ionic strength in 1 min. Such a shape memory hydrogel with self-healing ability and multi-stimuli-responsive properties will offer an option toward intelligent soft materials for biomedical and bionic research.

Dual-stimuli response of spiropyran derivative modified by long-chains: high-contrast photochromism and mechanochromism

A spiropyran derivative combines high-contrast solid-state photochromism and reversible mechanochromism is reported.

Thermo-mechanical reversibility in a shape memory organic salt

The dual-stimulus response behavior of organic crystals, exhibiting shape memory effects at slightly above body temperature, to thermal and mechanical stress was analyzed by stress–strain curves, crystallography, and solid-state NMR spectroscopy.

Polydopamine Nanoparticles Containing a Cisplatin Analog for Anticancer Treatment and Diagnostics

Cancer is a leading cause of death with rates expected to grow with life expectancy. Among leading treatments, cisplatin, widely used to combat cancer, suffers from low stability and selectivity. Here, we covalently conjugated an analog of cisplatin to biocompatible polydopamine nanoparticles (PDA-NPs) to increase both properties. Dynamic light scattering and electron microscopy studies suggest that the platinum-conjugated PDA particles (Pt–PDA-NPs) are monodispersed and spherical with a diameter of about 200 nm with platinum atoms mostly in the shell. Particles were also characterized with inductively coupled plasma mass atomic emission spectroscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy to determine the localization and amount of Pt atoms. The chelated metal did not leach from the conjugated particles under normal physiological conditions, while it was released only under acidic and oxidative conditions existing predominantly inside lysosomes and near cancer cells, suggesting their dual-stimuli responsiveness. Fluorescent microscopy confirmed that Pt–PDA-NPs are localized in the endoplasmic reticulum and internalized into cancer cells by endosomes. In cell survival experiments, particles are more toxic to human MCF-7 breast cancer cells compared to healthy NIH-3T3 cells. Mechanistic studies confirmed that the anticancer activity was induced by increased apoptosis. Field-dependent magnetization measurements suggest that Pt–PDA-NPs with a Gd3+-modified surface are paramagnetic and detectable by MRI, suggesting their promising theranostic application in cancer treatment.

Bioinspired Eggosomes with Dual Stimuli-Responsiveness.

Hen's eggs have been designed through evolution to serve as a rich source of nutrients and to provide a protective environment for the developing embryo. As such, they have a unique composition and structural organization, consisting of an egg yolk, egg white, and eggshell. Inspired by nature, a biomimetic approach has been adopted in this study to create "micro-eggs" using the natural structure of hen's eggs as an inspiration. Our aim was to use these micro-eggs to encapsulate, protect, and release nutrients so they could be incorporated into functional foods to improve their nutritional value. These micro-eggs consist of an oily core surrounded by a protein-rich gel, which is then coated by a hard calcium carbonate (CaCO3) shell. Advanced emulsion technology and structural design principles were utilized to create these microscale egg-like structures (50-200 μm). In particular, a water-in-oil-in-water (W/O/W) double emulsion was formulated using natural materials found in eggs (lecithin, oleic acid, and albumin) to create the egg yolk/egg white structure. Then, a CaCO3 "eggshell" was fabricated in situ to stabilize the outer oil-water interface. The resulting micro-eggs were then successfully packaged into an "egg box" formed by calcium alginate. The packaged micro-eggs were shown to have good resistance to disruption or separation during storage. The thermo- and pH-responsive "egg yolk" was provided bioactive release "on-demand". We refer to these biomimetic micro-eggs as "eggosomes" in analogy to colloidosomes. The nutritionally fortified eggosomes developed here may be useful for the creation of functional foods specifically designed to improve human health and wellbeing.

Modulating acrylic acid content of nanogels for drug delivery & biocompatibility studies

Dual stimuli-responsive nanogels (NGs) have gained popularity in the field of bio medicine due to their versatile nature of applicability. Poly(N-isopropylacrylamide)-co-poly(acrylic acid) (pNIPAm-pAAc)-based NGs provide such dual stimuli-response with pNIPAm and pAAc providing thermal and pH-based responses, respectively. Studying the growth of these NGs, as well as, understanding the effect of the incorporation of pAAc in the NG matrix, is important in determining the physico-chemical properties of the NG. Studies have been conducted investigating the effect of increasing pAAc content in the NGs, however, these are not detailed in understanding its effects on the physico-chemical properties of the pNIPAm-pAAc-based NGs. Also, the biocompatibility of the NGs have not been previously reported using human whole blood model. Herein, we report the effect of different reaction parameters, such as surfactant amount and reaction atmosphere, on the growth of pNIPAm-pAAc-based NGs. It is shown that the size of the NGs can be precisely controlled from ~130 nm to ~400 nm, by varying the amount of surfactant and the reaction atmosphere. The effect of increasing incorporation of pAAc in the NG matrix on its physico-chemical properties has been investigated. The potential of these NGs as drug delivery vehicles is investigated by conducting loading and release studies of a model protein drug, cytochrome C (Cyt C) from the NGs at temperature above the volume phase transition temperature (VPTT) and acidic pH. An ex vivo human whole blood model was used to investigate biocompatibility of the NGs by quantifying inflammatory responses during NG exposure. The NGs did not induce any significant production of chemokine IL-8 or pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and the cell viability in human whole blood was maintained during 4 h exposure. The NGs did neither activate the complement system, as determined by low Terminal Complement Complex (TCC) activation and Complement Receptor 3 (CR3) activation assays, thereby overall suggesting that the NGs could be potential candidates for biomedical applications.

Recent Applications of Dual-Stimuli Responsive Chitosan Hydrogel Nanocomposites as Drug Delivery Tools.

Polysaccharides are a versatile class of macromolecules that are involved in many biological interactions critical to life. They can be further modified for added functionality. Once derivatized, these polymers can exhibit new chemical properties that can be further optimized for applications in drug delivery, wound healing, sensor development and others. Chitosan, derived from the N-deacetylation of chitin, is one example of a polysaccharide that has been functionalized and used as a major component of polysaccharide biomaterials. In this brief review, we focus on one aspect of chitosan’s utility, namely we discuss recent advances in dual-responsive chitosan hydrogel nanomaterials.