Zingiber officinale and thymus vulgaris extracts co-loaded polyvinyl alcohol and chitosan electrospun nanofibers for tackling infection and wound healing promotion.

Infections are severe complications associated with chronic wounds and tardy healing that should be timely treated to achieve rapid and proper tissue repair. To hinder such difficulties, a nanofibrous mat composed of polyvinyl alcohol and chitosan (PVA/CS) was developed by electrospinning method, containing thyme (Thymus vulgaris) and ginger (Zingiber officinale) extracts. The mat containing 10 wt% of the extracts (at the ratio of 50:50) exposed the nanofibers (NFs) with the nanoscale diameter (average 382 ± 60 nm), smooth surface, and defect-free morphology. Likewise, the relevant analyses of the loaded mat displayed high wettability, porosity, and liquid absorption capacity without any adverse interaction. The obtained mat also provided a high antioxidant activity, and its release profile was continuous and sustained for nearly 72 h. Besides, it inhibited the growth of both Gram-positive S. aureus and Gram-negative E. coli strains. Furthermore, the proposed mat significantly accelerated cutaneous wound healing in bacterial-infected rats by preventing bacteria growth at the wound site. At last, histopathology analysis confirmed the ample regeneration of skin structures, forming collagen fibers and appendages. Overall, the proposed mat containing ginger-thyme extracts provides multiple therapeutic capabilities with promising solutions for inhibiting wound infection and accelerating the healing process.

Demographic and biological factors in interrelationships between physical, cognitive, psychological, and social frailty in community-dwelling older adults: Data from the Birjand Longitudinal Aging Study (BLAS).

Complex interrelationships may exist among different types of frailty. This study aimed to evaluate the demographic and biological factors that influence the different types of frailty in community-dwelling older adults in Iran through a cross-sectional analysis of data obtained from the Birjand Longitudinal Aging Study. This study is an ongoing cohort study of people aged 60 years and over and employed a multistage stratified cluster random sampling. Anthropometric measures were obtained by nurses. The "Fried frailty phenotype" was defined as physical frailty. Cognitive frailty was assessed using the Mini-Mental State Examination. Social frailty was evaluated by some questions, and psychological frailty was assessed using a patient health questionnaire. Blood samples were taken after overnight fasting. All statistical analyses were performed using Stata12 (Texas, USA) and Python. Some type of frailty had been experienced by 62.27 % of the older adults. Cognitive frailty was the dominant type of frailty (55.69 %). Based on multivariate regression analysis, age, sex, education, and marital status were the influencing factors in all types of frailty. Network analysis revealed that physical, cognitive, psychological, and social frailty had synergistic effects on each other, and age and sex had dominant interactions with frailty types. Cognitive frailty was dominant compared with other types of frailty, indicating the need to detect cognitive frailty at the earliest stage and to implement an appropriate program to manage cognitive frailty in older adults.

Bromelain- and Silver Nanoparticle-Loaded Polycaprolactone/Chitosan Nanofibrous Dressings for Skin Wound Healing.

A cutaneous wound is caused by various injuries in the skin, which can be wrapped with an efficient dressing. Electrospinning is a straightforward adjustable technique that quickly and continuously generates nanofibrous wound dressings containing antibacterial and anti-inflammatory agents to promote wound healing. The present study investigated the physicochemical and biological properties of bromelain (BRO)- and silver nanoparticle (Ag NPs)-loaded gel-based electrospun polycaprolactone/chitosan (PCL/CS) nanofibrous dressings for wound-healing applications. Electron microscopy results showed that the obtained nanofibers (NFs) had a uniform and homogeneous morphology without beads with an average diameter of 176 ± 63 nm. The FTIR (Fourier transform infrared) analysis exhibited the loading of the components. Moreover, adding BRO and Ag NPs increased the tensile strength of the NFs up to 4.59 MPa. BRO and Ag NPs did not significantly affect the hydrophilicity and toxicity of the obtained wound dressing; however, the antibacterial activity against E. coli and S. aureus bacteria was significantly improved. The in vivo study showed that the wound dressing containing BRO and Ag NPs improved the wound-healing process within one week compared to other groups. Therefore, gel-based PCL/CS nanofibrous dressings containing BRO and Ag NPs could be a promising solution for healing skin wounds.

Current challenges ahead in preparation, characterization, and pharmaceutical applications of nanoemulsions.

Nanoemulsions (NEs) are emulsions with particle size of less than around 100 nm. Reviewing the literature, several reports are available on NEs, including preparation, characterization, and applications of them. This review aims to brief challenges that researchers or formulators may encounter when working with NEs. For instance, when selecting NE components and identifying their concentrations, stability and safety of the preparation should be evaluated. When preparing an NE, issues over scale-up of the preparation as well as possible effects of the preparation process on the active ingredient need to be considered. When characterizing the NEs, the two major concerns are accuracy of the method and accessibility of the characterizing instrument. Also a highly efficient NE for clinical use to deliver the active ingredient to the target tissue with maximum safety profile is commonly sought. Throughout the review we also have tried to suggest approaches to overcome the challenges. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies.

A systematic study of nano-based fibrous systems: Diagnostic and therapeutic approaches for dementia control.

Nano-based systems provide many advantages, including eluding gastrointestinal and first-pass metabolism of the drug and improving the potential advantage of reduced doses of drugs for an equal or better therapeutic effect compared to other parts of oral administration. Over the last few years, protein-based nanofibrous biomaterials have been used for better controlling dementia. PubMed, Scopus, and ISI Web of Science were consulted for available articles on nano-based fibrous systems for the treatment and diagnosis of dementia (up to October 2022). Of 725 articles that were identified and evaluated, only 19 were included. Eleven studies evaluated nanofibrous electrospun biomaterials for better dementia control. Among these, four investigated marker/biomarker detection for the early diagnosis of dementia. Two from four studies conducted hydrogel-based nanofibrous for Alzheimer's disease (AD) treatment. Additionally, four studies inspected stem cell (SC) transplantation on nano-based fibrous scaffolds for better treatment of dementia. Finally, two from the final four studies considered nano-based fibrous systems for the enhanced treatment of dementia. Our study concluded that nano-based fibrous platforms, exclusively peptide/protein-based nanofibrous scaffolds made from biomaterials, can be applied for dementia management by either diagnostic or therapeutic approaches specific in purpose-designed electrospun nanofibrous scaffolds.

Functionalized SPION immobilized on graphene-oxide: Anticancer and antiviral study.

The progressive and fatal outbreak of some diseases such as cancer and coronavirus necessitates using advanced materials to bring such devastating illnesses under control. In this study, graphene oxide (GO) is decorated by superparamagnetic iron oxide nanoparticles (SPION) (GO/SPION) as well as polyethylene glycol functionalized SPION (GO/SPION@PEG), and chitosan functionalized SPION (GO/SPION@CS). Field emission scanning electron microscopic (FESEM) images show the formation of high density uniformly distributed SPION nanoparticles on the surface of GO sheets. The structural and chemical composition of nanostructures is confirmed by X-ray diffraction and Fourier transform infrared spectroscopy. The saturation magnetization of GO/SPION, GO/SPION@PEG and GO- SPION@CS are found to be 20, 19 and 8 emu/g using vibrating sample magnetometer. Specific absorption rate (SAR) values of 305, 283, and 199 W/g and corresponding intrinsic loss power (ILP) values of 9.4, 8.7, and 6.2 nHm2kg-1 are achieved for GO/SPION, GO/SPION@PEG and GO/SPION@CS, respectively. The In vitro cytotoxicity assay indicates higher than 70% cell viability for all nanostructures at 100, 300, and 500 ppm after 24 and 72 h. Additionally, cancerous cell (EJ138 human bladder carcinoma) ablation is observed using functionalized GO/SPION under applied magnetic field. More than 50% cancerous cell death has been achieved for GO/SPION@PEG at 300 ppm concentration. Furthermore, Surrogate virus neutralization test is applied to investigate neutralizing property of the synthesized nanostructures through analysis of SARS-CoV-2 receptor-binding domain and human angiotensin-converting enzyme 2 binding. The highest level of SARS-CoV-2 virus inhibition is related to GO/SPION@CS (86%) due to the synergistic exploitation of GO and chitosan. Thus, GO/SPION and GO/SPION@PEG with higher SAR and ILP values could be beneficial for cancer treatment, while GO/SPION@CS with higher virus suppression has potential to use against coronaviruses. Thus, the developed nanocomposites have a potential in the efficient treatment of cancer and coronavirus.

Random and Positional Immobilization of Multi-enzyme Systems.

In recent years, three key techniques including random co-immobilization, positional co-immobilization, and compartmentalization for multi-enzyme immobilization were extensively considered. Herein, we investigate random co-immobilization and positional co-immobilization techniques for multi-enzyme systems in detail. We describe randomly co-immobilized glucose oxidase (GOx) and horseradish peroxidase (HRP) on reduced graphene oxide (rGO) as the most used methods. Materials and methods are presented in terms of preparation of GO and rGO as well as enzyme immobilization procedure. Moreover, the principles of positional co-immobilization have been reviewed, and the relevant methods based on microfluidic systems and DNA structure considering HRP and GOx enzymes have been individually studied. It is believed that the benefits of using the methods associated with random and specifically positional immobilized multi-enzyme systems include not only enhanced cascade enzymatic activity via manipulated surface such as microfluidic systems (including porous materials) and DNA structure but also improved enzyme stability and ease of recovery for recycle.

Compartmentalized Immobilization of Multi-enzyme Systems.

The methods of compartmentalized immobilization in multi-enzyme systems containing inorganic complexes and organic scaffolds (i.e. nucleic acid (RNA and DNA), protein and lipid) have been thoroughly investigated. Compartmentalization mostly focuses on dividing individual enzyme(s) into specific location or orientation of the enzymes cooperating in cascade reaction. Organic scaffolds are preferred because of their capability for simultaneous synthesis in biological systems. Besides, the most required methods of horseradish peroxidase (HRP) and glucose oxidase (GOD) enzymes including enzyme activity measurement, enzyme immobilization, removal, and re-hybridization, and enzyme attaching have been provided because they have been extensively applied in multi-enzyme systems. Organic scaffolds have a wide range and properties. Therefore, two methods including dockerin-cohesin linker and nucleotides interaction have been demonstrated for immobilization of enzyme on protein and DNA scaffold, respectively.

Interactive relationship between Trp metabolites and gut microbiota: The impact on human pathology of disease.

Tryptophan (Trp), an α-amino acid, is the precursor of serotonin (5-hydroxytryptamine, 5-HT), which is involved in a variety of features of metabolic function and human nutrition. Evidence highlights the role of Trp metabolites (exclusively 5-HT) in the gastrointestinal (GI) tract; however, the mechanisms of action involved in the release of 5-HT in the GI tract are still unknown. Considering the fact that variations of 5-HT may facilitate the growth of certain GI disorders, gaining a better understanding of the function and release of 5-HT in the GI tract would be beneficial. Additionally, investigating Trp metabolism may clarify the relationship between Trp and gut microbiota. It is believed that other metabolites of Trp (mostly that of the kynurenine pathway) may play a significant role in controlling gut microbiota function. In this review, we have attempted to summarize the current research investigating the relationship of gut microbiota, Trp and 5-HT metabolism (with particular attention paid to their metabolite type, as well as a discussion of the research methods used in each study). Taking together, regarding the role that Trp/5-HT plays in a range of physical and mental diseases, the gut bacterial types, as well as the related disorders, have been exclusively considered.

A hyaluronic acid/PVA electrospun coating on 3D printed PLA scaffold for orthopedic application.

The need for bone tissue replacement, repair and regeneration for orthopedic application is constantly growing. Therefore, the application of cartilage substitute due to the lack of donors as well as biocompatibility leads to immune system rejection. In order to overcome these drawbacks, researchers have used porous scaffold as an option for bone transplantation. In this study, poly-lactic acid (PLA) scaffolds were prepared for cartilage application by fused deposition modeling (FDM) technique and then coated by electrospinning with polyvinyl alcohol (PVA) and hyaluronic acid (HLA) fibers. Hybrid electrospinning (ELS) method was used to produce porous scaffolds from HLA-PVA polymers. The printed scaffold was coated using FDM technique and the mechanical and biological investigation was performed on the polymeric composite specimen. The functional group and morphological behavior were investigated using Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) techniques. The obtained porous scaffold has hydrophilic properties as the PVA and HLA were coated on the PLA. The porous 3D-printed scaffold containing PLA/PVA/HLA scaffold does not show any toxicity in MTT evaluation after 1, 3 and 7 days. The SEM image confirmed the cell adhesion of the chondrite to the scaffold. Also, the mechanical performances of the sample, such as elastic modulus and compressive strength, were evaluated by compression test. By electro-spun coating, the elastic module of PVA/PLA and PLA/PVA/HLA scaffolds has increased to 18.31 ± 0.29 MPa and 19.25 ± 0.38 MPa. Also, the tensile strength of these two porous scaffolds has reached 6.11 ± 0.42 MPa and 6.56 ± 0.14 MPa, respectively. The failure strain of 3D printed PLA scaffold was reported to be 53 ± 0.21% and this value was reduced to 47 ± 0.62% and 42 ± 0.22% in PVA/PLA and PLA/PVA/HLA scaffolds. The cells' growth on the porous scaffolds showed a broad, spindle-shaped and regular shape. The obtained results of the chemical, physical and biological analyses showed that porous PLA/PVA/HLA scaffold has potential applications in cartilage construction.

Nanofiber-based systems intended for diabetes.

Diabetic mellitus (DM) is the most communal metabolic disease resulting from a defect in insulin secretion, causing hyperglycemia by promoting the progressive destruction of pancreatic ß cells. This autoimmune disease causes many severe disorders leading to organ failure, lower extremity amputations, and ultimately death. Modern delivery systems e.g., nanofiber (NF)-based systems fabricated by natural and synthetic or both materials to deliver therapeutics agents and cells, could be the harbinger of a new era to obviate DM complications. Such delivery systems can effectively deliver macromolecules (insulin) and small molecules. Besides, NF scaffolds can provide an ideal microenvironment to cell therapy for pancreatic ß cell transplantation and pancreatic tissue engineering. Numerous studies indicated the potential usage of therapeutics/cells-incorporated NF mats to proliferate/regenerate/remodeling the structural and functional properties of diabetic skin ulcers. Thus, we intended to discuss the aforementioned features of the NF system for DM complications in detail.

Nanobiocide Based-Silver Nanomaterials Upon Coronaviruses: Approaches for Preventing Viral Infections.

The effectiveness of silver nanomaterials (AgNMs), as antiviral agents, has been confirmed in humans against many different types of viruses. Nanobiocides-based AgNMs can be effectively applied to eliminate coronaviruses (CoVs), as the cause of various diseases in animals and humans, particularly the fatal human respiratory infections. Mostly, these NMs act effectively against CoVs, thanks to the NMs' fundamental anti-viral structures like reactive oxygen species (ROS), and photo-dynamic and photo-thermal abilities. Particularly, the antiviral activity of AgNMs is clarified under three inhibitory mechanisms including viral entry limitation, attachment inhibition, and viral replication limitation. It is believed that nanobiocide with other possible materials such as TiO2, silica and, carbon NMs exclusively nano-graphene materials can emerge as a more effective disinfectant for long-term stability with low toxicity than common disinfectants. Nanobiocides also can be applied for the prevention and treatment of viral infections specifically against COVID-19.

Serotonin level as a potent diabetes biomarker based on electrochemical sensing: a new approach in a zebra fish model.

Serotonin (5-HT) levels have been associated with several exclusively metabolic disorders. Herein, a new approach for 5-HT level as a novel biomarker of diabetes mellitus is considered using a simple nanocomposite and HPLC method. Reduced graphene oxide (rGO) comprising gold nanoparticles (AuNPs) was decorated with 18-crown-6 (18.Cr.6) to fabricate a simple nanocomposite (rGO-AuNPs-18.Cr.6). The nanocomposite was positioned on a glassy carbon electrode (GCE) to form an electrochemical sensor for the biomarker 5-HT in the presence of L-tryptophan (L-Trp), dopamine (DA), ascorbic acid (AA), urea, and glucose. The nanocomposite exhibited efficient catalytic activity for 5-HT detection by square-wave voltammetry (SWV). The proposed sensor displayed high selectivity, excellent reproducibility, notable anti-interference ability, and long-term stability even after 2 months. SWV defined a linear range of 5-HT concentration from 0.4 to 10 µg L-1. A diabetic animal model (diabetic zebrafish model) was then applied to investigate 5-HT as a novel biomarker of diabetes. A limit of detection (LOD) of about 0.33 µg L-1 was found for the diabetic group and 0.15 µg L-1 for the control group. The average levels of 5-HT obtained were 9 and 2 µg L-1 for control and diabetic groups, respectively. The recovery, relative standard deviation (RSD), and relative error (RE) were found to be about 97%, less than 2%, and around 3%, respectively. The significant reduction in 5-HT level in the diabetic group compared to the control group proved that the biomarker 5-HT can be applied for the early diagnosis of diabetes mellitus.

Determination of the biomarker L-tryptophan level in diabetic and normal human serum based on an electrochemical sensing method using reduced graphene oxide/gold nanoparticles/18-crown-6.

A novel nanocomposite-modified electrode based on reduced graphene oxide (rGO) decorated with 18-crown-6 (Cr.6) and gold nanoparticles (GNPs) on the surface of a glassy carbon electrode (GCE) was successfully fabricated to investigate the electrochemical sensing of the biomarker L-tryptophan (L-Trp) in the presence of dopamine (DA), ascorbic acid (AA), urea, and glucose. The rGO-GNPs-Cr.6/GCE displayed high electrochemical catalytic activity for L-Trp determination using square-wave voltammetry (SWV). The electrochemical behavior of L-Trp at the rGO-GNPs-Cr.6/GCE displayed higher oxidation current and potential (oxidation peak current of 40 µA at 0.85 V) than rGO-GNPs/GCE, Cr.6/GCE, GNPs/GCE, rGO/GCE, and bare GCE. The SWV demonstrated a linear range of L-Trp concentration from 0.1 to 2.5 µM. A low limit of detection (LOD) was found for L-Trp, with LOD of about 0.48 µM and 0.61 µM in diabetic and normal serum, respectively. The fabricated sensor demonstrated high selectivity and sensitivity, and good stability and reproducibility for L-Trp sensing. Finally, the nanocomposite (rGO-GNPs-Cr.6)-modified GCE was applied for the determination of L-Trp in normal and diabetic human serum samples, and displayed excellent LOD and recoveries higher than 91.8%. Graphical Abstract.

Investigation of chitosan-g-PEG grafted nanoparticles as a half-life enhancer carrier for tissue plasminogen activator delivery.

Tissue plasminogen activator (tPA) a thrombolytic agent is commonly used for digesting the blood clot. tPA half-life is low (4-6 min) and its administration needs a prolonged continuous infusion. Improving tPA half-life could reduce enzyme dosage and enhance patient compliance. Nano-carries could be used as delivery systems for the protection of enzymes physically, enhancing half-life and increasing the stability of them. In this study, chitosan (CS) and polyethylene glycol (PEG) were used for the preparation of CS-g-PEG/tPA nanoparticles (NPs) via the ion gelation method. Particles' size and loading capacity were optimised by central composite design. Then, NPs cytotoxicity, release profile, enzyme activity and in vivo half-life and coagulation time were investigated. The results showed that NPs does not have significant cytotoxicity. Release study revealed that a burst effect happened in the first 5 min and resulted in releasing 30% of tPA. Loading tPA in NPs could decrease 25% of its activity but the half-life of it increases in comparison to free tPA in vivo. Also, blood coagulation time has significantly affected (p-value = 0.041) by encapsulated tPA in comparison to free tPA. So, CS-g-PEG/tPA could increase enzyme half-life during the time and could be used as a non-toxic candidate delivery system for tPA.

Electrochemical detection of serotonin: A new approach.

Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter which plays a significant role in various functions in the body, such as appetite, emotions, and autonomic functions. It is well known that biomarker 5-HT levels can be correlated to several diseases and disorders such as depression, anxiety, irritable bowel, and sleep trouble. Among various methods for detecting the 5-HT biomarker, electrochemical techniques have attracted great interest due to their low cost and ease of operation. However, sensitive and precise electrochemical detection of 5-HT levels is not possible using bare electrodes, thus requiring electrode modification. The present review aims to describe the different electroanalytical methods for 5-HT detection using various surface-modified electrodes such as glassy carbon, carbon fiber, diamond, graphite, and metal electrodes modified with conductive polymers. Perspectives and the modification of electrode surface using applied polymers for 5-HT detection have also been presented.

Preparation of PEG-grafted chitosan/streptokinase nanoparticles to improve biological half-life and reduce immunogenicity of the enzyme.

Streptokinase, as a thrombolytic drug, is widely used in treatment of cardiovascular disorders and deep vein thrombosis. Streptokinase is immunogenic due to its prokaryotic source, having short biological half-life (i.e. 15 to 30 min) that is not enough for an efficient therapy. In this study, nanoparticles (NPs) of chitosan/streptokinase and polyethylene glycol (PEG)-grafted chitosan/streptokinase were prepared by polyelectrolyte complex method. Particle size of chitosan and PEG-grafted chitosan NPs were 154 ± 42 and 211 ± 47 nm, respectively. Results showed that using PEG in preparation of nanoparticles leads to ~24% decrease in encapsulation efficiency. Encapsulation of streptokinase in the NPs also resulted in a slight reduction in enzymatic activity. However, in vivo findings indicated that response of the immune system was delayed for 20 days and blood circulation time of the enzyme increased up to 120 min by using PEG. Biological half-life of the drug also increased up to twice in PEG-grafted chitosan. In conclusion, PEG-grafted chitosan NPs could be an alternative for delivery of streptokinase to reduce its clinical limitations.

Gold-capped mesoporous silica nanoparticles as an excellent enzyme-responsive nanocarrier for controlled doxorubicin delivery.

Mesoporous silica nanoparticles (MSNs) have ideal characteristics as next generation of controlled drug delivery systems. In this study, a MSN-based nanocarrier was fabricated and gold nanoparticle (GNP)-biotin conjugates were successfully grafted onto the pore outlets of the prepared MSN. This bioconjugate served as a capping agent with a peptide-cleavable linker sensitive to matrix metalloproteinases (MMPs), which are overexpressed extracellular proteolytic enzymes in cancerous tissue. The prepared nanocarriers were fully characterised by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption, Fourier transform infra-red spectroscopy (FTIR), dynamic light scattering (DLS) and thermo gravimetric analysis (TGA). In vitro release studies showed efficient capping of MSNs with gold gate and controlled release of Doxorubicin (DOX) in the presence of matrix metalloproteinase-2 (MMP-2) and acidic pH values. High DOX-loading capacity (21%) and encapsulation efficiency (95.5%) were achieved using fluorescence technique. DOX-loaded nanocarriers showed high cytocompatibility and could efficiently induce cell death and apoptosis in the MMP-2 overexpressed cell lines. Moreover, Haemolysis, platelet activation and inflammatory responses assessment approved excellent hemocompatibility and minimal side effects by encapsulation of DOX in MSNs carrier.

Nanomaterial based electrochemical sensing of the biomarker serotonin: a comprehensive review.

This review (with 131 references) summarizes the progress made in the past years in the field of nanomaterial based sensing of serotonin (5-HT). An introduction summarizes the significant role of 5-HT as a biomarker for several major diseases, methods for its determination and the various kinds of nanomaterials for use in electrochemical sensing process relies principally on a precise choice of electrodes. The next main section covers nanomaterial based methods for sensing 5-HT, with subsections on electrodes modified with carbon nanotubes, graphene related materials, gold nanomaterials, and by other nanomaterials. A concluding section discusses future perspectives and current challenges of 5-HT determination. Graphical abstract Conceptual design of electrochemical sensing process of the biomarker serotonin by using nanomaterials and the role of 5-HTas biomarker in the body from preclinical to clincal.

Theranostic α-Lactalbumin-Polymer-Based Nanocomposite as a Drug Delivery Carrier for Cancer Therapy.

A nanotheranostic system was developed using α-lactalbumin along with Fe3O4 nanoparticles as an magnetic resonance imaging (MRI) contrast agent for medical imaging and doxorubicin as the therapeutic agent. α-lactalbumin was precipitated and cross-linked using poly(ethylene glycol) and glutaraldehyde. Besides, polyethylenimine was applied to increase the number of amine groups during cross-linking between α-lactalbumin and Fe3O4 nanoparticles. Interestingly, 90% of the initial protein used for the coaggregation process was incorporated in the prepared 130 nm nanocomposites, which facilitated the 85% doxorubicin loading. Formation of pH-sensitive imine bonds between glutaraldehyde and amine groups on α-lactalbumin and polyethylenimine resulted in higher release of doxorubicin at acidic pHs and consequently development of a pH-sensitive nanocarrier. The designed nanocomposite was less immunogenic owing to stimulating the production of less amounts of C3a, C5a, platelet factor 4, glycoprotein IIb/IIIa, platelet-derived ß-thromboglobulin, interleukin-6, and interleukin-1ß compared to the free doxorubicin. Furthermore, 1000 µg/mL nanocomposite led to 0.2% hemolytic activity, much less than the 5% standard limit. The void nanocarrier induced no significant level of cytotoxicity in breast cancer and normal cells following 96 h incubation. The doxorubicin-loaded nanocomposite presented higher cytotoxicity, apoptosis induction, and doxorubicin uptake in cancer cells than free doxorubicin. Conversely, lower cytotoxicity, apoptosis induction, and doxorubicin uptake were observed in normal cells treated with the doxorubicin-loaded nanocarrier compared to free doxorubicin. In line with the results of in vitro experiments, in vivo studies on tumor-bearing mice showed more suppression of tumor growth by the doxorubicin-loaded nanocomposite compared to the free drug. Moreover, the pharmacokinetic study revealed slow release of doxorubicin from the nanocomposite. Besides, in vitro and in vivo MRI studies presented a higher r2/r1 ratio and comparable contrast to the commercially available DOTAREM, respectively. Our findings suggest that this new nanocomposite is a promising nanotheranostic system with promising potential for cancer therapy and diagnosis.