Bottlebrush Polymers for Articular Joint Lubrication: Influence of Anchoring Group Chemistry on Lubrication Properties.

The role of carboxylic, aldehyde, or epoxide groups incorporated into bottlebrush macromolecules as anchoring blocks (or cartilage-binding blocks) is investigated by measuring their lubricating properties and cartilage-binding effectiveness. Mica modified with amine groups is used to mimic the cartilage surface, while bottlebrush polymers functionalized with carboxylic, aldehyde, or epoxide groups played the role of the lubricant interacting with the cartilage surface. We demonstrate that bottlebrushes with anchoring blocks effectively reduce the friction coefficient on modified surfaces by 75-95% compared to unmodified mica. The most efficient polymer appears to be the one with epoxide groups, which can react spontaneously with amines at room temperature. In this case, the value of the friction coefficient is the lowest and equals 0.009 ± 0.001, representing a 95% reduction compared to measurements on nonmodified mica. These results show that the presence of the functional groups within the anchoring blocks has a significant influence on interactions between the bottlebrush polymer and cartilage surface. All synthesized bottlebrush polymers are also used in the preliminary lubrication tests carried out on animal cartilage surfaces. The developed materials are very promising for future in vivo studies to be used in osteoarthritis treatment.

Development of New Resolvin D1 Analogues for Osteoarthritis Therapy: Acellular and Computational Approaches to Study Their Antioxidant Activities.

In osteoarthritis (OA), oxidative stress plays a crucial role in maintaining and sustaining cartilage degradation. Current OA management requires a combination of pharmaceutical and non-pharmacological strategies, including intraarticular injections of hyaluronic acid (HA). However, several lines of evidence reported that HA oxidation by reactive oxygen species (ROS) is linked with HA cleavage and fragmentation, resulting in reduced HA viscosity. Resolvin D1 (RvD1) is a lipid mediator that is biosynthesized from omega-3 polyunsaturated fatty acids and is a good candidate with the potential to regulate a panoply of biological processes, including tissue repair, inflammation, oxidative stress, and cell death in OA. Herein, newly designed and synthesized imidazole-derived RvD1 analogues were introduced to compare their potential antioxidant properties with commercially available RvD1. Their antioxidant capacities were investigated by several in vitro chemical assays including oxygen radical absorbance capacity, 2,2-diphenyl-1-picrylhydrazyl radical scavenging, ferric ion reducing antioxidant power, hydroxyl radical scavenging, and HA fragmentation assay. All results proved that imidazole-derived RvD1 analogues showed excellent antioxidant performance compared to RvD1 due to their structural modifications. Interestingly, they scavenged the formed reactive oxygen species (ROS) and protected HA from degradation, as verified by agarose gel electrophoresis and gel permission chromatography. A computational study using Gaussian 09 with DFT calculations and a B3LYP/6-31 G (d, p) basis set was also employed to study the relationship between the antioxidant properties and chemical structures as well as calculation of the molecular structures, frontier orbital energy, molecular electrostatic potential, and bond length. The results showed that the antioxidant activity of our analogues was higher than that of RvD1. In conclusion, the findings suggest that imidazole-derived RvD1 analogues can be good candidates as antioxidant molecules for the treatment of oxidative stress-related diseases like OA. Therefore, they can prolong the longevity of HA in the knee and thus may improve the mobility of the articulation.

Chitosan-based biomaterials for the treatment of bone disorders.

Bone is an alive and dynamic organ that is well-differentiated and originated from mesenchymal tissues. Bone undergoes continuous remodeling during the lifetime of an individual. Although knowledge regarding bones and their disorders has been constantly growing, much attention has been devoted to effective treatments that can be used, both from materials and medical performance points of view. Polymers derived from natural sources, for example polysaccharides, are generally biocompatible and are therefore considered excellent candidates for various biomedical applications. This review outlines the development of chitosan-based biomaterials for the treatment of bone disorders including bone fracture, osteoporosis, osteoarthritis, arthritis rheumatoid, and osteosarcoma. Different examples of chitosan-based formulations in the form of gels, micro/nanoparticles, and films are discussed herein. The work also reviews recent patents and important developments related to the use of chitosan in the treatment of bone disorders. Although most of the cited research was accomplished before reaching the clinical application level, this manuscript summarizes the latest achievements within chitosan-based biomaterials used for the treatment of bone disorders and provides perspectives for future scientific activities.

Oncostatic activities of melatonin: Roles in cell cycle, apoptosis, and autophagy.

Melatonin, the major secretory product of the pineal gland, not only regulates circadian rhythms, mood, and sleep but also has actions in neoplastic processes which are being intensively investigated. Melatonin is a promising molecule which considered a differentiating agent in some cancer cells at both physiological and pharmacological concentrations. It can also reduce invasive and metastatic status through receptors MT1 and MT2 cytosolic binding sites, including calmodulin and quinone reductase II enzyme, and nuclear receptors related to orphan members of the superfamily RZR/ROR. Melatonin exerts oncostatic functions in numerous human malignancies. An increasing number of studies report that melatonin reduces the invasiveness of several human cancers such as prostate cancer, breast cancer, liver cancer, oral cancer, lung cancer, ovarian cancer, etc. Moreover, melatonin's oncostatic activities are exerted through different biological processes including antiproliferative actions, stimulation of anti-cancer immunity, modulation of the cell cycle, apoptosis, autophagy, the modulation of oncogene expression, and via antiangiogenic effects. This review focuses on the oncostatic activities of melatonin that targeted cell cycle control, with special attention to its modulatory effects on the key regulators of the cell cycle, apoptosis, and telomerase activity.

Oncostatic activities of melatonin: Roles in cell cycle, apoptosis, and autophagy.

Melatonin, the major secretory product of the pineal gland, not only regulates circadian rhythms, mood, and sleep but also has actions in neoplastic processes which are being intensively investigated. Melatonin is a promising molecule which considered a differentiating agent in some cancer cells at both physiological and pharmacological concentrations. It can also reduce invasive and metastatic status through receptors MT1 and MT2 cytosolic binding sites, including calmodulin and quinone reductase II enzyme, and nuclear receptors related to orphan members of the superfamily RZR/ROR. Melatonin exerts oncostatic functions in numerous human malignancies. An increasing number of studies report that melatonin reduces the invasiveness of several human cancers such as prostate cancer, breast cancer, liver cancer, oral cancer, lung cancer, ovarian cancer, etc. Moreover, melatonin's oncostatic activities are exerted through different biological processes including antiproliferative actions, stimulation of anti-cancer immunity, modulation of the cell cycle, apoptosis, autophagy, the modulation of oncogene expression, and via antiangiogenic effects. This review focuses on the oncostatic activities of melatonin that targeted cell cycle control, with special attention to its modulatory effects on the key regulators of the cell cycle, apoptosis, and telomerase activity.

Rational design of smart nano-platforms based on antifouling-nanomaterials toward multifunctional bioanalysis.

The ability to design nanoprobe devices with the capability of quantitative/qualitative operation in complex media will probably underpin the main upcoming progress in healthcare research and development. However, the biomolecules abundances in real samples can considerably alter the interface performance, where unwanted adsorption/adhesion can block signal response and significantly decrease the specificity of the assay. Herein, this review firstly offers a brief outline of several significances of fabricating high-sensitivity and low-background interfaces to adjust various targets' behaviors induced via bioactive molecules on the surface. Besides, some important strategies to resist non-specific protein adsorption and cell adhesion, followed by imperative categories of antifouling reagents utilized in the construction of high-performance solid sensory interfaces, are discussed. The next section specifically highlights the various nanocomposite probes based on antifouling-nanomaterials for electrode modification containing carbon nanomaterials, noble metal nanoparticles, magnetic nanoparticles, polymer, and silicon-based materials in terms of nanoparticles, rods, or porous materials through optical or chemical strategies. We specially outline those nanoprobes that are capable of identification in complex media or those using new constructions/methods. Finally, the necessity and requirements for future advances in this emerging field are also presented, followed by opportunities and challenges.

Molecular bottlebrush with pH-responsive cleavable bonds as a unimolecular vehicle for anticancer drug delivery.

Drug delivery systems with targeted and smart properties have emerged as an efficient strategy to overcome the challenges of cancer chemotherapy such as toxic side effects and the development of multidrug resistance. In this study, a biocompatible bottlebrush polymer poly((3-(2-bromo-2-methylpropionate)propyldimethylsilyloxy)ethyl methacrylate)-graft-poly(2-methacryloyloxyethyl phosphorylcholine) P(BIBS-EMA)-g-PMPC with pH-responsive silanol cleavable bond was designed and developed for delivery of doxorubicin. A549 cell line of human lung carcinoma was tested. The synthesized bottlebrush polymer was analyzed and characterized via Fourier transform infrared spectroscopy, FTIR, nuclear magnetic resonance spectroscopy, 1H NMR, gel permeation chromatography, GPC, dynamic laser light scattering, DLS, and static laser light scattering, SLS, techniques. The cleavage process was also precisely studied to confirm the pH-responsiveness of such bottlebrush polymers. In vitro loading and release studies of doxorubicin as a model drug were examined and the results showed a pH-dependent release manner with a twice higher release rate under cancerous tissue conditions compared to standard physiological conditions. MTT cytotoxicity assay was also performed to prove the biocompatibility of the designed polymeric platform on healthy human cells. Due to the presence of bio-inspired poly(2-methacryloyloxyethyl phosphorylcholine) side chains in the prepared bottlebrush polymer, the formed polymer-drug complex could also exhibit effective internalization into tumor cells. These facts further support the potential use of this carrier in drug delivery applications and for further in vivo studies.

Were magnetic materials useful in cancer therapy?

Cancer is one of the major challenges fronting the biomedical basic researches in our time. The study and development of effective therapeutic strategies for cancer therapy are vital. Among the many probable core constituents of nanoparticles, magnetite-based nanoparticles have been widely studied for cancer therapy owing to their inherent magnetic features, multifunctional design, biodegradable and biocompatible properties. Magnetic nanoparticles have been also designed for utilizing as contrast enhancer agents for magnetic resonance imaging, drug delivery systems, and most recently as a therapeutic element in inducing cellular death in tumor ablation therapies. This review aimed to provide an overview of the various applications of magnetic nanoparticles and recent achievements in developing these advanced materials for cancer therapy.

Novel Methotrexate-Ciprofloxacin Loaded Alginate-Clay Based Nanocomposite as Anticancer and Antibacterial Co-Drug Delivery System.

Purpose: In last decades, by increasing multi-drug resistant microbial pathogens an urgent demand was felt in the development of novel antimicrobial agents. Methods: Promising nanocomposites composed of clay/alginate/imidazolium-based ionic liquid, have been developed via intercalation of calcium alginate and ionic liquid by ion exchange method. These tailored nanocomposites were used as nanocarriers to simultaneously deliver methotrexate (MTX), and ciprofloxacin (CIP), as anticancer and antibacterial agents, respectively to MCF-7 breast cancer cells. Nanocomposites were fully characterized by scanning electron microscopy studies (SEM), X-ray diffraction (XRD), Fourier transforms infrared (FTIR) spectroscopy, and thermogravimetric analysis (TGA) methods. The in vitro antimicrobial potential of the mentioned nanocomposites in free and dual-drug loaded form was investigated on Pseudomonas aeruginosa and Escherichia coli bacteria. The antitumor activity of nano-formulations was evaluated by both MTT assay and cell cycle arrest. Results: The dual drug-loaded nanocomposites with exceptionally high loading efficiency (MTX: 99 ±0.4% and CIP: 98 ±1.2%) and mean particle size of 70 nm were obtained with obvious pH-responsive MTX and CIP release (both drugs release rate was increased at pH 5.8 compared to 7.4). The antibacterial activity of CIP-loaded nanocomposites was significantly higher in comparison with free CIP (P <0.001). The antitumor activity results revealed that MTX cytotoxicity on MCF-7 cells was significantly higher in nano-formulations compared to free MTX (P <0.001). Both MTX-loaded nanocomposites caused S-phase arrest in MCF-7 cells compared to non-treated cells (P ˂ 0.001). Conclusion: Newly developed smart nanocomposites are potentially effective pH-sustainable delivery systems for enhanced tumor therapy.

Antimicrobial bio-nanocomposite films based on gelatin, tragacanth, and zinc oxide nanoparticles - Microstructural, mechanical, thermo-physical, and barrier properties.

Gelatin and tragacanth were employed to fabricate antimicrobial nanocomposites with 1, 3, and 5% zinc oxide nanoparticles (ZnO-NPs). FT-IR and XRD proved new chemical interactions among GEL/TGC/ZnO-NPs and higher crystallinity of nanocomposites, respectively. DSC showed a significant increase in melting point temperature (Tm) from ~ 90 to ~ 93-101 °C after adding 1-5% ZnO-NPs. Ultimate tensile strength (UTS) was remarkably increased to 31.21, 34.57, and 35.06 MPa, as well as Young's Modulus to 287.44, 335.47, and 367.04 MPa after incorporating 1, 3, and 5% ZnO-NPs. The ZnO-NPs dose-dependently reduced the water vapor permeability (WVP) of the films. FE-SEM analysis from surface and cross-section illustrated the compact and homogenous structure of the nanocomposites even up to 5% ZnO-NPs. The ZnO-NPs-containing nanocomposites had a good antimicrobial activity (~10-20 mm) against both Staphylococcus aureus and Escherichia coli. Generally, the results indicated that the prepared nanocomposite films are promising antimicrobial bio-materials for food packaging.

Recent developments in natural and synthetic polymeric drug delivery systems used for the treatment of osteoarthritis.

Osteoarthritis (OA), is a common musculoskeletal disorder that will progressively increase in older populations and is expected to be the most dominant cause of disability in the world population by 2030. The progression of OA is controlled by a multi-factorial pathway that has not been completely elucidated and understood yet. However, over the years, research efforts have provided a significant understanding of some of the processes contributing to the progression of OA. Both cartilage and bone degradation processes induce articular cells to produce inflammatory mediators that produce proinflammatory cytokines that block the synthesis of collagen type II and aggrecan, the major components of cartilage. Systemic administration and intraarticular injection of anti-inflammatory agents are the first-line treatments of OA. However, small anti-inflammatory molecules are rapidly cleared from the joint cavity which limits their therapeutic efficacy. To palliate this strong technological drawback, different types of polymeric materials such as microparticles, nanoparticles, and hydrogels, have been examined as drug carriers for the delivery of therapeutic agents to articular joints. The main purpose of this review is to provide a summary of recent developments in natural and synthetic polymeric drug delivery systems for the delivery of anti-inflammatory agents to arthritic joints. Furthermore, this review provides an overview of the design rules that have been proposed so far for the development of drug carriers used in OA therapy. Overall it is difficult to state clearly which polymeric platform is the most efficient one because many advantages and disadvantages could be pointed to both natural and synthetic formulations. That requires further research in the near future.

Para-sulfonatocalix[n]arene-based biomaterials: Recent progress in pharmaceutical and biological applications.

The history, properties, and characteristics of para-sulfonato-calixarenes are described. On the one hand, the inherent antibacterial and antifungal properties against microorganisms, and on the other hand non-toxicity of these supramolecules toward human organs are analyzed. The resulting biocompatibility of para-sulfonato-calixarenes makes them potential candidates for diverse life sciences and pharmaceutical applications without significant side effects. The interactions with different drugs, the capability of drug encapsulation, delivery, and release, the formation of host-quest assemblies and inclusion complexation between para-sulfonato-calixarenes and drugs were also investigated in detail. Besides, their function in cancer treatment and their toxicity against different cancer cell lines were fully reviewed and summarized. Afterward, the capability of these macrocyclic compounds for biosensing of organic compounds, peptides and enzymes activity was highlighted. In this review, we also take a brief look at recent reports on the applications of para-sulfonato-calixarenes in fluorescence imaging and their usage as highly stable and bright probes for in vivo and in vitro imaging and sensing.

Overcoming multidrug resistance in cancer: Recent progress in nanotechnology and new horizons.

Multidrug resistance (MDR), defined as the ability of cancer cells to gain resistance to both conventional and novel chemotherapy agents, is an important barrier in treating malignancies. Initially, it was discovered that cellular pumps dependent on ATP were the cause of resistance to chemotherapy, and further studies have found that other mechanisms such as increased metabolism of drugs, decreased drug entry, and defective apoptotic pathways are involved in this process. MDR has been the focus of numerous initiatives and countless studies have been undertaken to better understand MDR and formulate strategies to overcome its effects. The current review highlights various nano-drug delivery systems including polymeric/solid lipid/mesoporous silica/metal nanoparticles, dendrimers, liposomes, micelles, and nanostructured lipid carriers to overcome the mechanism of MDR. Nanoparticles are novel gateways to enhance the therapeutic efficacy of anticancer agents at the target site of action due to their tumor-targeting abilities, which can limit the unwanted systemic effects of chemotherapy agents and also reduce drug resistance. Additionally, other innovative strategies including RNA interference as a biological process used to inhibit or silence specific gene expression, natural products as MDR modulators with little systemic toxic effects, which interfere with the functions of proteins involved in drug efflux, and physical approaches such as combination of conventional drug administration with thermal/ultrasound/photodynamic strategies are also highlighted.

Carbohydrate polymer-based silver nanocomposites: Recent progress in the antimicrobial wound dressings.

Wound healing is a dynamic and complex process which affects the quality of life in patients and annually causes high costs for the health system, worldwide. Polymers from natural origins such as polysaccharides have gained particular interest between researchers for wound dressing applications due to their abundance in nature, biocompatibility with human tissues, and ideal physicochemical properties. Aside from their supportive effect in wound care, polysaccharides and their derivatives can actively contribute to the healing process. Silver nanoparticles are widely used noble metal nanoparticles incorporated in wound dressings due to their low toxicity for human cells, naturally availability, and strong antimicrobial effects. In the present study, we will review the most frequently used polysaccharides in wound dressing procedure with silver or silver nanoparticles accommodated. The methods of synthesis, physicochemical properties, healing efficiencies, toxicity against human tissues, antibacterial and antifungal effects of each material will also be discussed.

Graphene quantum dot cross-linked carboxymethyl cellulose nanocomposite hydrogel for pH-sensitive oral anticancer drug delivery with potential bioimaging properties.

Herein, graphene quantum dots (GQDs) were introduced as a novel and safe crosslinker for carboxymethyl cellulose to make biodegradable and biocompatible hydrogels. The casting was used as a simple method for the preparation of the CMC/GQDs films. Effects of the GQDs percentage on the physicochemical properties of the films were studied, and several characterizations were performed including Fourier transform infrared spectroscopy, UV-vis spectroscopy, scanning electron microscopy, gas permeability, and mechanical testing analysis. The CMC/GQDs showed a pH-sensitive swelling and degradation with improved tensile strength. Fluorescent properties were also studied to evaluate the potential of the prepared CMC/GQDs nanocomposite for fluorescent bioimaging applications. Drug delivery property of the CMC-GQDs were studied using doxorubicin (DOX) as a model anticancer drug. Cytotoxicity studies were carried out using human colon adenocarcinoma HT29 cells. The prepared CMC/GQDs exhibited biocompatibility and pH-sensitive drug delivery behavior which proposed the prepared nanocomposite hydrogel has the potential to be used as a pH-triggered site-specific drug delivery system.

Needle-shaped amphoteric calix[4]arene as a magnetic nanocarrier for simultaneous delivery of anticancer drugs to the breast cancer cells.

BACKGROUND: Chemotherapy as an important tool for cancer treatment faces many obstacles such as multidrug resistance and adverse toxic effects on healthy tissues. Drug delivery systems has opened a new window to overcome these problems. There has been a strong interest development of new platform and system for delivof chemotherapeutic agents. PURPOSE: In the present study, a green synthesis method was chosen and performed for preparation of a novel amphoteric calix[4]arene (Calix) macrocycle with low toxicity to the human body. MATERIALS AND METHODS: The amphoteric Calix was coated on the surface of Fe3O4 magnetic nanoparticles and used as a magnetic nanocarrier for simultaneous delivery of two anticancer agents, doxorubicin and methotrexate, against MCF7 cancer cells. Several chemical characterizations were done for validation of prepared nanocarrier, and in vitro loading and release studies of drugs were performed with good encapsulation efficiency. RESULTS: In vitro biological studies including hemolysis assay, erythrocytes sedimentation rate, red blood cells aggregation, cyto cellular internalization, and apoptosis evaluations were performed. Based on results, the developed nanocarrier has many advantages and capability for an efficient codelivery of DOX and MTX, which has a highly potent ability to kill cancer cells. CONCLUSION: All these results persuade us, this nanocarrier could be effectively used for cancer therapy of MCF7 breast cancer cells and is suitable for use in further animal studies in future investigations.

New potentials for 3-hydroxy-3-methyl-glutaryl-coenzymeA reductase inhibitors: Possible applications in retarding diabetic complications.

The prevalence of diabetes mellitus is increasing all over the world and it is apparent that treatment of diabetic complications has the same importance as primary diabetes treatment and glycemic control. Diabetic complications occur as a result of prolonged hyperglycemia and its consequences, such as advanced glycation end products and reactive oxygen species. Impairment of lipid profile is also contributed to worsening diabetic complications. Therefore, it seems that the application of lipid-lowering agents may have positive effects on reversing diabetic complications besides glycemic control. Statins, a group of lipid-lowering compounds, have been shown to exert antioxidant, immunomodulatory, anti-inflammatory, and antiproliferative properties beyond their lipid-lowering effects. Furthermore, they have been reported to improve diabetic complications with different pathways. In this review, we will discuss the clinical importance, molecular biology of the most important microvascular/macrovascular diabetic complications, possible application of statins and their mechanism of action in retarding these complications.

A novel bioactive quaternized chitosan and its silver-containing nanocomposites as a potent antimicrobial wound dressing: Structural and biological properties.

Wound care is crucial for controlling infections of the injured area. Regarding this, wound dressings with antimicrobial activities are useful to minimize the microbial infections of the wounds. Herein, a series of quaternized chitosan nanocomposite films blended with silver nanoparticles were fabricated with high potential for wound dressing applications. After characterization of the prepared films by Fourier-transform infrared spectroscopy (FTIR), X-Ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and element mapping analysis (MAP). Other parameters such as swelling ratio, blood clotting activity, and biocompatibility of the films were also investigated. Besides, the antibacterial and antifungal activities of prepared samples were examined against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and a multi drug resistance Pseudomonas aeruginosa as a drug resistance bacterium strain. Interestingly, the designed quaternized chitosan film (even without silver nanoparticles) showed high antimicrobial activity against all tested microbial strains which is probably due to the presence of imidazolium moiety in the film matrix. Furthermore, all nanocomposites showed a potent antimicrobial activity. Generally, the results of cell proliferation and attachment with MTT assay and DAPI staining on HFFF cells, have proved the cytocompatibility nature of the nanocomposite films. These results indicate that the developed bioactive quaternized chitosan nanocomposite films can be considered as biomaterial for wound dressing applications.

Nanocrystalline cellulose: Preparation, physicochemical properties, and applications in drug delivery systems.

Cancer is the leading cause of death all over the world and chemotherapy is an important approach to fight cancer, however, there are many obstacles against successful cancer chemotherapy such as development of multidrug resistance, poor solubility of chemotherapeutic agents and adverse side effects to healthy tissues. An important strategy to overcome these obstacles, is the use of nanotechnology. In recent years, natural polymers such as cellulose and its nanoform structure, nanocrystalline cellulose (NCC), have attracted the interest of researchers in the field of nanotechnology and specially drug delivery systems, due to biocompatibility and biodegradability of NCC. Cellulose is the most abundant natural biopolymer and changes to NCC by several chemical and mechanical methods. In this review, we mainly focus on the methods for production of NCC, physicochemical properties and medical applications of NCC (e.g. regenerative medicine, replacement of vascular grafts, tissue engineering, anti-bacterial/anti-viral applications, diagnosis and biosensing) with a special emphasize on drug delivery systems.

Polyelectrolyte Carboxymethyl Cellulose for Enhanced Delivery of Doxorubicin in MCF7 Breast Cancer Cells: Toxicological Evaluations in Mice Model.

PURPOSE: Chemotherapy as an important tool for cancer treatment faces many obstacles such as multidrug resistance and adverse toxic effects on healthy tissues. Drug delivery systems have opened a new window to overcome these problems. METHODS: A polyelectrolyte carboxymethyl cellulose polymer as a magnetic nanocarrier was synthesized for enhancing delivery and uptake of doxorubicin in MCF7 breast cancer cells and decreasing the adverse toxic effects to healthy tissues. RESULTS: The physicochemical properties of developed nanocarrier showed that it can be used in drug delivery purposes. The efficiency of the delivery system was assessed by loading and release studies. Besides, biological assays including protein-particle interaction, hemolysis assay, cytotoxicity study, cellular uptake, and apoptosis analysis were performed. All results persuaded us to investigate the cytotoxic effects of nanocarrier in an animal model by determining the biochemical parameters attributed to organ injuries, and hematoxylin and eosin (H&E) staining for histopathological manifestations. We observed that the nanocarrier has no toxic effect on healthy tissues, while, it is capable of reducing the toxic side effects of doxorubicin by more cellular internalization. CONCLUSION: Chemical characterizations and biological studies confirmed that developed nanocarrier with permanent cationic groups of imidazolium and anionic carboxylic acid groups is an effective candidate for anticancer drug delivery.