Chitosan Base Research Articles

Enhanced photodynamic inactivation against Escherichia coli O157:H7 provided by chitosan/curcumin coating and its application in food contact surfaces

Sterilisation technologies are essential to eliminate foodborne pathogens from food contact surfaces. However, most of the current sterilisation methods involve high energy and chemical consumption. In this study, a photodynamic inactivation coating featuring excellent antibacterial activity was prepared by dispersing curcumin as a plant-based photosensitiser in a chitosan solution. The coating generated abundant reactive oxygen species (ROS) after light irradiation at 420 nm, which eradicated ≥99.999 % of Escherichia coli O157:H7. It was also found that ROS damaged the cell membrane, leading to the leakage of cell contents and cell shrinkage on the basis of chitosan. In addition, the production of ROS first excited the bacterial antioxidant defence system resulting in the increase of peroxidase (POD) and superoxide dismutase (SOD). ROS levels exceed its capacity, causing damage to the defence system and further oxidative decomposition of large molecules, such as DNA and proteins, eventually leading to the death of E. coli O157:H7. We also found the curcumin/chitosan coating could effectively remove E. coli O157:H7 biofilms by oxidative of extracellular polysaccharides and proteins. All the contributors made the chitosan/curcumin coating an efficient detergent comparable with HClO.

Release kinetics and biological properties of active films based on cellulose nanocrystal-chitosan in combination with γ-irradiation to mitigate microbial load in rice

Nanoemulsions (NEs) of two antimicrobial formulations (AF-1 and AF-2), a mixture of essential oils and citrus extracts, were prepared by microfluidization. For optimization, a central composite design was used to ascertain the effect of independent variables (pressure, number of cycles, and emulsifier concentration) on the physical properties of NEs [i.e., droplet size (DS), polydispersity index (PDI), zeta potential (ζ), and encapsulation efficiency (EE)] and compare with coarse emulsion. The optimized AF-1 and AF-2 values had DS of 116 and 40 nm, PDI of 0.17 and 0.2, ζ-potential of 49 and 32.3 mV, and EE of 77 and 79%, respectively. The microbicidal properties of the NEs against Escherichia coli O157:H7, Salmonella Typhimurium, Aspergillus niger, Penicillium chrysogenum, and Mucor circinelloides were significantly (P ≤ 0.05) higher than the coarse emulsion. The NEs of both AFs were incorporated into a chitosan-based (CH) film. In situ tests with rice using bioactive CH-based nanocomposite films (BCHNF) reinforced with cellulose nanocrystals (CNCs) were tested against selected bacteria and fungi with and without γ-irradiation (750Gy) and stored for eight weeks. The BCHNF alone reduced 50–71 % of bacterial and fungal growth compared to the controls, while the combined action of γ-irradiation and films reduced 73–93 % of the tested microbial growth compared to untreated controls. Incorporation of CNC into BCHNF demonstrated a predictable pattern of slower release of active components (32–39 %) over the eight week period compared to the bioactive films without CNC. The sensory qualities of rice did not change significantly after BCHNF treatments.

UV- shielding and antioxidant properties of chitosan film impregnated with Acacia catechu modified with calcium carbonate for food packaging

Acacia catechu contains polyphenolic compounds such as catechin and tannins, which exhibit antioxidant and antimicrobial properties that have the potential to be used in food packaging applications. In this study, chitosan-based (CH) antioxidant films were developed with the incorporation of calcium carbonate (CC) and Acacia catechu (CT). The films were fabricated by the solvent-casting method, and the effects of the different concentrations of Acacia catechu were analyzed. The physicomechanical, antioxidant, and UV shielding properties of the films were determined. The addition of Acacia catechu and calcium carbonate has significantly increased the tensile from 2.30 MPa to 4.95 MPa, respectively, for neat CH and CH/CC/CT-4 film. At the same time, there is a reduction in the elongation at break from 26.75 % in neat CH film to 12.11 % in CH/CC/CT-4 film. The CH/CC/CT-4 film has shown the highest ferric-reducing antioxidant power (FRAP) of 0.440 mg Trolox/g dried weight of the film and 2,2 diphenyl picrylhydrazyl (DPPH) radical scavenging activity of 93.05 %. The UV transmittance of CH/CC/CT-4 film was 0.46 %, the lowest compared to the rest of the fabricated films. These active properties depict that CH/CC/CT-4 film has the potential to be utilized for the packaging of light and oxygen-sensitive food products.

Glucose and UA sensing based on Cu nanoparticle decorated Nif/GO flexible electrode.

Anovel, green, and facile approach has been developed to construct an ultrasensitive flexible enzyme-less electrochemical sensor on the basis of chitosan and graphene oxide composites decorated with Cu nanoparticles supported on nickel foam (Nif/Cs/GO@Cu), in which GO functions as the intermediate between Nif and Cu nanoparticles. The Nif/Cs/GO@Cu sensing platform was successfully fabricated by thedrop casting method to load Cs/GO onto Nif followed by an additionally electrodeposition to support Cu nanoparticles on Nif/Cs/GO. Impressively, the Nif/Cs/GO@Cu exhibited much higher electrocatalytic activity for glucose and UA oxidation as compared to that of Nif or Nif@Cu. For glucose and UA at about 0.6V and 0.1V (vs. Ag/AgCl), linearity could be obtained in the concentrationranges 5µM-4mM and 5-345µM;the sensitivities were16 and 2.5 µA µM-1cm-2, and the detection limits 83nM and 0.3 µM, respectively. The improved performance ofthe composite electrode was ascribed to the synergistic effect of Cu nanoparticles, Nif and GO, in which GO provides high electron conductivity and large surface area to prevent the agglomeration of Cu nanoparticles; Cu nanoparticles and Nif offer abundant active sites towards analytes oxidation. Additionally, the method was applied to determine both analytes successfully in blood serum samples with excellent recovery and also opens up an attractive route to potential applications of theflexible nickel foam-based electrochemical sensor.

EFFECT OF ORANGE PEEL ESSENTIAL OIL ON THE PROPERTIES OF CHITOSAN: GELATIN CASTED FILMS PREPARED FOR ACTIVE PACKAGING

Food packaging is a passive barrier that protects food against environmental factors such as ultraviolet light, oxygen, water vapor, pressure, heat, chemical, and microbiological contaminants. In a changing and developing world, consumers now want to reach healthier, fresher, and more diverse foods. In response to consumer demands and expectations, the food sector has focused on developing active and intelligent packaging. The purpose of active packaging is to protect the properties of the food by interacting with the coating material and prolonging the shelf life. In this context, it is aimed to prepare active package films by integrating bioactive agents into films prepared based on biodegradable polymers. It is an important point that is determined how the characteristics of the films such as morphology, molecular structure, surface property, and antimicrobial activity, will shift depending on the type and quantity of bioactive agent addition. Based on this, packaging films loaded with different concentrations of orange peel essential oil (OEO) (25, 50 and 100% of total polymer weight) were produced on the basis of chitosan and gelatin natural polymers. The changes that occur in the active films as a result of the increasing amounts of oil were revealed by determining the molecular structure, surface property, morphological characteristics, solubility quality, and antibacterial activity. The solubility of the films, which is an effective parameter in the evaluation of the environmental impact of the films that will be released as waste after use, varied between 20% and 25% at the end of 48 hours. The 100OEO@CH:GEL film showed the highest antibacterial properties against Escherichia coli and Staphylococcus aureus.

Poly(limonene): A novel renewable oligomeric antioxidant and UV-light blocking additive for chitosan-based films

Limonene is a well-known bioactive additive for biopolymer-based films. However, its high volatility considerably limits such applications. Herein, we propose the use of a low molecular weight poly(limonene) (PLM) as an alternative high-performance additive for chitosan-based (CH) films. Effects of different concentrations (0.15–0.45 % w/w) of PLM on the properties of CH films were systematically evaluated. Overall, films with impressive antioxidant activity and UV light barrier were easily obtained, even at reduced PLM loads. Among the concentrations explored, there was a reduction in the film’s tensile strength from 23.73 to 12.08 MPa, when the maximum concentration of PLM (0.45 %) was used. However, the elongation at break did not change significantly for any sample. Additionally, the water vapor transmission rate decreased from approximately 547 to 412 g m−2 day−1. Therefore, PLM demonstrates the potential to appear as a novel high-stability additive for active bio-based film development serving food packaging.

Multifunctional antibacterial chitosan-based hydrogel coatings on Ti6Al4V biomaterial for biomedical implant applications

Among biomedical community, great efforts have been realized to develop antibacterial coatings that avoid implant-associated infections. To date, conventional mono-functional antibacterial strategies have not been effective enough for successful long-term implantations. Consequently, researchers have recently focused their attention on novel bifunctional or multifunctional antibacterial coatings, in which two or more antibacterial mechanisms interact synergistically. Thus, in this work different chitosan-based (CHI) hydrogel coatings were created on Ti6Al4V surface using genipin (Ti-CHIGP) and polyethylene glycol (Ti-CHIPEG) crosslinking agents. Hydrogel coatings demonstrated an exceptional in vivo biocompatibility plus a remarkable ability to promote cell proliferation and differentiation. Lastly, hydrogel coatings demonstrated an outstanding bacteria-repelling (17–28 % of S. aureus and 33–43 % of E. coli repelled) and contact killing (186–222 % of S. aureus and 72–83 % of E. coli damaged) ability. Such bifunctional antibacterial activity could be further improved by the controlled release of drugs resulting in powerful multifunctional antibacterial coatings.

Chitosan-Based Edible Coatings Containing Essential Oils to Preserve the Shelf Life and Postharvest Quality Parameters of Organic Strawberries and Apples during Cold Storage.

Edible coatings and films have been researched for more than three decades due to their ability to be incorporated with different functional ingredients or compounds as an option to maintain the postharvest quality of fruits and vegetables. The aim of this study was to evaluate the effect of three types of chitosan-based (CH) edible coatings obtained from medium and high molecular weight chitosan, containing ascorbic or acetic acid and sea buckthorn or grape seed essential oils on the physical-chemical and microbiological properties of organic strawberries and apple slices during cold storage at 4 °C and 8 °C. Scanning electron microscope images showed both a smooth structure and a fracture and pore structure on strawberry coatings and a dense and smooth structure on the apple slices coatings. Further, the edible coatings managed to reduce the microbial load of yeasts and molds of the coated strawberries during the storage period. Overall, the treatments preserved the ascorbic acid, total polyphenol content, and antioxidant activity for all the tested samples compared to the control sample, throughout the storage period. In addition, the water activity (aw) of the coated samples presented lower values (0.96-0.98) than the control samples. The obtained results indicate that the developed chitosan-based edible coatings could maintain the postharvest parameters of the tested samples, also leading to their shelf-life prolongation.

Novel Epigenetic Modulation Chitosan-Based Scaffold as a Promising Bone Regenerative Material.

Bone tissue engineering is a complicated field requiring concerted participation of cells, scaffolds, and osteoactive molecules to replace damaged bone. This study synthesized a chitosan-based (CS) scaffold incorporated with trichostatin A (TSA), an epigenetic modifier molecule, to achieve promising bone regeneration potential. The scaffolds with various biphasic calcium phosphate (BCP) proportions: 0%, 10%, 20%, and 40% were fabricated. The addition of BCP improved the scaffolds’ mechanical properties and delayed the degradation rate, whereas 20% BCP scaffold matched the appropriate scaffold requirements. The proper concentration of TSA was also validated. Our developed scaffold released TSA and sustained them for up to three days. The scaffold with 800 nM of TSA showed excellent biocompatibility and induced robust osteoblast-related gene expression in the primary human periodontal ligament cells (hPDLCs). To evaluate in vivo bone regeneration potential, the scaffolds were implanted in the mice calvarial defect model. The excellent bone regeneration ability was further demonstrated in the micro-CT and histology sections compared to both negative control and commercial bone graft product. New bone formed in the CS/BCP/TSA group revealed a trabeculae-liked characteristic of the mature bone as early as six weeks. The CS/BCP/TSA scaffold is an up-and-coming candidate for the bone tissue engineering scaffold.

OBTAINING EYE FILMS BASED ON CHITOSAN

This work presents data on the study of the possibility of using the natural polysaccharide chitosan and a synthetic polymer of polyvinyl alcohol as a matrix for creating a polymer form in the form of a film with prolonged drug release. Eye films based on chitosan, as well as on the basis of chitosan and polyvinyl alcohol, have been developed by obtaining a composite injection. The immobilization of antibiotics in polyvinyl alcohol films leads to a pro nounced prolongation of the antibiotic action, at the same time, it significantly increases the penetration of the drug into the tissues and eye fluids, providing the necessary therapeutic concentration for 1 day, which certainly becomes a significant advantage of antibiotic administration methods. To study the yield of drugs from polymer dosage forms, the method of UV spectroscopy was used. The influence of the concentration of drugs on the dynamics of their release from polymer films in «in vitro» conditions was studied. It was found that their chitosan / PVA film has a longer release of the drug, which is indicative of a prolongation effect. The results which were obtained indicate the possibility of using a dosage form based on biocompatible high molecular weight compounds to create therapeutic systems with a diffusion mechanism of drug release.

Development of red apple pomace extract/chitosan-based films reinforced by TiO2 nanoparticles as a multifunctional packaging material

A chitosan-based (CS) film was developed with nanosized TiO2 and red apple pomace extract (APE). The intermolecular interactions of CS, TiO2 and APE were evaluated by Fourier transform infrared spectroscopy, scanning electron microscopy and X-ray diffraction. TiO2 nanoparticles remarkably improved the water vapor and UV–Vis light barrier properties, mechanical strength and thermal stability of CS-APE films. The strong antioxidant abilities of CS-APE and CS-TiO2-APE films were characterized. Nano-TiO2 and APE showed a synergistic enhancement of the antimicrobial activity in CS matrix. The addition of TiO2 nano-particles into CS-APE films resulted the sensitive color variations, which applied successfully as an indicator to monitor the freshness of salmon fillets. Consequently, the development of CS-APE-TiO2 film provides a new solution to convert rad apple pomace to an active and multifunctional food packaging material with considerable mechanical, antibacterial, antioxidant and pH-responsive color-changing properties.

Antioxidant and antibacterial polyelectrolyte wound dressing based on chitosan/hyaluronan/phosphatidylcholine dihydroquercetin

Antioxidant and antimicrobial wound dressings are the most favorable for acute and chronic wounds treatment. Herein, we formulated a multifunctional polyelectrolyte wound dressing membrane on the basis of chitosan (Ch) and hyaluronan (HA) enhanced by phosphatidylcholine dihydroquercetin (PCDQ). Physicochemical properties and microstructures of fabricated films were investigated adopting Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA) and scanning electron microscope (SEM). Furthermore, water uptakes, wettability profiles, surface roughness, and mechanical characteristics of the developed membranes were studied. The developed wound dressing revealed free radical scavenging potency, hemocompatibility with a tendency to enhance blood clotting. Furthermore, incorporation of PCDQ significantly promoted the antibacterial and anti-inflammatory activities of Ch/HA/PCDQ. Moreover, Ch/HA/PCDQ films exhibited cellular compatibility towards mouse fibroblast cells. The capability of Ch/HA/PCDQ to promote wound healing was evaluated using adult Wistar albino female rats. The in vivo findings demonstrated that Ch/HA/PCDQ films significantly ameliorated mouse full-thickness wounds as evidenced by a reduction in the wound area. Moreover, histological examinations of wounds dressed with Ch/HA/PCDQ illustrated a prominent re-epithelialization compared with wounds handled with the cotton gauze and Ch/HA dressings, exposing the efficiency of PCDQ. These findings emphasized that a Ch/HA/PCDQ membrane has outstanding potential for wound healing and skin regeneration.

Biodegradable double cross-linked chitosan hydrogels for drug delivery: Impact of chemistry on rheological and pharmacological performance

This study investigates the impact of dual ionic and covalent cross-links (ion-XrL and cov-XrL) on the properties of chitosan-based (CTS) hydrogels as eco-friendly drug delivery systems (DDS) for the model drug diclofenac sodium (DCNa). Citric acid and a diiodo-trehalose derivative (ITrh) were the chosen ionic and covalent cross-linker, respectively. The novel hydrogels completely disintegrated within 96 h by means of a hydrolysis process mediated by the enzyme trehalase. As far as the authors are aware, this is the first time that a trehalose derivative has been used as a covalent cross-linker in the formation of biodegradable hydrogels. The impact of CTS concentration and degree of cov-XrL on rheological parameters were examined by means of an experimental model design and marked differences were found between the materials. Hydrogels with maximum elastic properties were achieved at high CTS concentrations and high degrees of cov-XrL. DCNa-loaded formulations displayed well-controlled drug-release profiles strongly dependent on formulation composition (from 17% to 40% in 72 h). Surprisingly, higher degrees of covalent cross-linking led to a boost in drug release. The formulations presented herein provides a simple and straightforward pathway to design fully biodegradable, tailor-made controlled drug delivery systems with improved rheological properties.

Development of curcumin-loaded chitosan/pluronic membranes for wound healing applications

The emergence of new materials with improved antibacterial, anti-inflammatory and healing properties compared to conventional wound dressings has both social and economic appeal. In this study, novel chitosan-based (CTS) membranes containing curcumin (CUR) incorporated in Pluronic (PLU) copolymers were developed and characterized to obtain suitable properties for applications as a wound healing dressing. The mechanical, thermal, swelling, wettability, release and permeation properties were evaluated by DSC, TGA, water contact angle measurements, FTIR, fluorescence and microscopic techniques. Membranes containing PLU and CUR presented wettability close to the ideal range for interaction with cellular components (contact angle ~40–70°), improved mechanical properties, higher thermal stability, high swelling degree (>800%) and CUR release (~60%) compared to samples without PLU addition. A higher retention of CUR in the epidermis than in the dermis layer was observed, which also was confirmed by confocal microscopy. Furthermore, the CTS-PLU membranes loaded with CUR showed to be active against Staphylococcus aureus and Pseudomonas aeruginosa (MIC = 25 and 100 mg mL−1, respectively), the microbial species most present in chronic wounds. Overall, the CTS-PLU-CUR membranes presented suitable properties to act as a new wound healing dressing formulation and in vivo studies should be performed to confirm these benefits.

Immune Response to Salmonella Enteritidis Infection in Broilers Immunized Orally With Chitosan-Based Salmonella Subunit Nanoparticle Vaccine.

Salmonella enterica serovar Enteritidis (S. Enteritidis, SE) infection in broilers causes a huge economic loss and public health risk. We previously demonstrated that orally delivered chitosan based (CS) Salmonella subunit nanoparticle (NP) vaccine containing immunogenic outer membrane proteins (OMP) and flagellin (FLA) of SE [CS-NP(OMP+FLA)] induces immune response in broilers. The objective of this study was to evaluate the dose- and age-dependent response and efficacy of CS-NP(OMP+FLA) vaccine in broilers. Three-day old birds were vaccinated and boosted once or twice. Additional groups were vaccinated at three weeks with no booster or boosted once a week later. Each dose of CS-NP vaccine had either 10 or 50 μg of OMP+FLA antigens. Our data revealed that two doses of vaccine were required to induce substantial immune response. Birds received 2 doses of CS-NP(OMP+FLA) vaccine at 3 days and 3 weeks of age with 10 μg antigens, and birds inoculated twice at 3 and 4 weeks of age with 50 μg antigens had lowest challenged bacterial load in the cecal contents with over 0.5 log10 reduction. In CS-NP(OMP+FLA) vaccinated birds, antigen-specific splenocyte proliferation, mucosal and systemic antibody response and the frequency of IFNγ-producing T cells were increased compared to control groups. At the molecular level, in the cecal tonsils of CS-NP(OMP+FLA) immunized birds, mRNA levels of toll-like receptor (TLR) 2 and TLR 4, and cytokines IL-4 and IL-10 were upregulated. The CS-NP(OMP+FLA) vaccine given orally has the potential to induce a protective immune response against SE infection in broilers.

Norfloxacin-Loaded Electrospun Scaffolds: Montmorillonite Nanocomposite vs. Free Drug.

Infections in nonhealing wounds remain one of the major challenges. Recently, nanomedicine approach seems a valid option to overcome the antibiotic resistance mechanisms. The aim of this study was the development of three types of polysaccharide-based scaffolds (chitosan-based (CH), chitosan/chondroitin sulfate-based (CH/CS), chitosan/hyaluronic acid-based (CH/HA)), as dermal substitutes, to be loaded with norfloxacin, intended for the treatment of infected wounds. The scaffolds have been loaded with norfloxacin as a free drug (N scaffolds) or in montmorillonite nanocomposite (H—hybrid-scaffolds). Chitosan/glycosaminoglycan (chondroitin sulfate or hyaluronic acid) scaffolds were prepared by means of electrospinning with a simple, one-step process. The scaffolds were characterized by 500 nm diameter fibers with homogeneous structures when norfloxacin was loaded as a free drug. On the contrary, the presence of nanocomposite caused a certain degree of surface roughness, with fibers having 1000 nm diameters. The presence of norfloxacin–montmorillonite nanocomposite (1%) caused higher deformability (90–120%) and lower elasticity (5–10 mN/cm2), decreasing the mechanical resistance of the systems. All the scaffolds were proven to be degraded via lysozyme (this should ensure scaffold resorption) and this sustained the drug release (from 50% to 100% in 3 days, depending on system composition), especially when the drug was loaded in the scaffolds as a nanocomposite. Moreover, the scaffolds were able to decrease the bioburden at least 100-fold, proving that drug loading in the scaffolds did not impair the antimicrobial activity of norfloxacin. Chondroitin sulfate and montmorillonite in the scaffolds are proven to possess a synergic performance, enhancing the fibroblast proliferation without impairing norfloxacin’s antimicrobial properties. The scaffold based on chondroitin sulfate, containing 1% norfloxacin in the nanocomposite, demonstrated adequate stiffness to sustain fibroblast proliferation and the capability to sustain antimicrobial properties to prevent/treat nonhealing wound infection during the healing process.

Poplar Hot Water Extract Enhances Barrier and Antioxidant Properties of Chitosan/Bentonite Composite Film for Packaging Applications.

Herein, the chitosan-based (CS) composite film was fabricated via a simple and efficient blending approach by adding poplar hot water extract (HWE), bentonite (BT) and chitosan. The addition of HWE largely improved the UV blocking ability and antioxidant properties of the resultant composite film, and simultaneously a tortuous path was constructed within the chitosan matrix to enhance the water vapor and oxygen barriers after the addition of BT. Specially, the content of HWE at 10 wt % gave a greatly decreased UV light transmittance at 280 nm to the CS-BT-HWE composite film that was 99.36% lower than that of CS-BT film, and the oxidation resistance was 9.65 times higher than that of CS-BT. The mechanical properties and surface morphological observation evaluated by scanning electron microscopy (SEM) and scanning probe microscope (SPM) confirmed the film had a denser structure. The internal chemical structure analyzed using solid state NMR, FTIR and X-ray spectra exhibited the resultant Maillard structure and strong hydrogen bonding that contributed to the improved mechanical properties. Overall, the as-prepared composite film has great potential as food packaging materials, and also provides a high-efficient utilization pathway for HWE.

Selective photodegradation of atrazine by a novel molecularly imprinted nanophotocatalyst prepared on the basis of chitosan

An imprinted molecular nanophotocatalyst was synthesized by use of chitosan as polymer, epichlorohydrin as cross-linker, and atrazine as molecular template. The photocatalyst was identified by XRD, SEM, and FTIR techniques. UV–Vis diffuse reflectance spectroscopy and photoluminescence analysis were employed to study the optical property of the synthesized photocatalyst. The total organic carbon analysis, high performance liquid chromatography, and gas chromatography methods were used to evaluate the degradation efficiency and to identify the decomposition fragments. The Molecularly imprinted nanophotocatalyst exhibited much higher selectivity and efficiency compared to its non-imprinted counterpart for atrazine. Optimizing of affecting variables was performed by RSM and the results indicated that under optimized condition 80.29% of the pollutant was degraded.

Enzymatic Destruction of Film Materials on the Basis of Chitosan in the Presence of Cephalosporin Series Antibiotics

Enzymatic Destruction of Film Materials on the Basis of Chitosan in the Presence of Cephalosporin Series Antibiotics

A novel chitosan-based nanomedicine for multi-drug resistant breast cancer therapy

In this study, a novel chitosan-based (CS) nanocarrier was developed for doxorubicin (DOX) and oleanolic acid (OA) co-delivery. CS was first functionalized with folic acid to allow selective uptake by cancer cells, and then subsequently with OA. The resultant copolymer self-assembled into nanoparticles (NPs) upon addition to water. These FA-CS-g-OA@DOX nanoparticles (NPs) had appropriate size (180 nm) and size distribution (PDI < 0.45) for tumor therapy, as well as a high drug-loading efficiency (15.6% w/w DOX; 5.1% w/w OA) and pH-responsive release properties. In breast cancer MDA-MB-231 cells, more efficient uptake of FA-CS-g-OA@DOX NPs than of free DOX was observed by confocal laser scanning microscopy and flow cytometry. The in vitro cytotoxicity of FA-CS-g-OA@DOX NPs against MDA-MB-231 cells was higher than with free DOX and free OA, while the NPs were less harmful to healthy HUVEC cells. In vivo pharmacokinetic studies showed that FA-CS-g-OA@DOX NPs had a much longer circulation time than free DOX, while biodistribution results revealed that FA-CS-g-OA@DOX could actively target a MDA-MB-231 xenograft tumor in mice. The NPs are found to have apoptosis-enhancing and anti-proliferative capacities in vivo. The presence of OA in the formulation both sensitizes cancer cells to DOX and mitigates DOX-induced damage to healthy tissues. The FA-CS-g-OA@DOX NPs generated in this work hence have great potential for the treatment of multi-drug resistant breast cancers, and further offer a platform to target other cancers.