Cerium oxide nanoparticles: Synthesis methods and applications in wound healing.

Wound care and treatment can be critical from a clinical standpoint. While different strategies for the management and treatment of skin wounds have been developed, the limitations inherent in the current approaches necessitate the development of more effective alternative strategies. Advances in tissue engineering have resulted in the development of novel promising approaches for accelerating wound healing. The use of various biomaterials capable of accelerating the regeneration of damaged tissue is critical in tissue engineering. In this regard, cerium oxide nanoparticles (CeO2 NPs) have recently received much attention because of their excellent biological properties, such as antibacterial, anti-inflammatory, antioxidant, and angiogenic features. The incorporation of CeO2 NPs into various polymer-based scaffolds developed for wound healing applications has led to accelerated wound healing due to the presence of CeO2 NPs. This paper discusses the structure and functions of the skin, the wound healing process, different methods for the synthesis of CeO2 NPs, the biological properties of CeO2 NPs, the role of CeO2 NPs in wound healing, the use of scaffolds containing CeO2 NPs for wound healing applications, and the potential toxicity of CeO2 NPs.

Facile preparation of silver based radiosensitizers via biomineralization method for enhanced in vivo breast cancer radiotherapy.

To solve the traditional radiotherapy obstacles, and also to enhance the radiation therapy efficacy various radiosensitizers have been developed. Radiosensitizers are promising agents that under X-ray irradiation enhance injury to tumor tissue by accelerating DNA damage. In this report, silver-silver sulfide nanoparticles (Ag-Ag2S NPs) were synthesized via a facile, one-pot and environmentally friendly biomineralization method. Ag-Ag2S was coated with bovine serum albumin (BSA) in situ and applied as an X-ray sensitizer to enhance the efficiency of radiotherapy. Also, folic acid (FA) was conjugated to Ag-Ag2S@BSA to impart active targeting capability to the final formulation (Ag-Ag2S@BSA-FA). Prepared NPs were characterized by transmission electron microscopes (TEM), scanning electron microscope (SEM), dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-Vis), X-ray diffraction analysis (XRD), and X-ray photoelectron spectroscopy (XPS) techniques. Results show that most of the NPs have well-defined uniform Janus structures. The biocompatibility of the NPs was then evaluated both in vitro and in vivo. A series of in vitro assays were performed on 4T1 cancer cells to evaluate the therapeutic efficacy of the designed NPs. In addition, the radio-enhancing ability of the NPs was tested on the 4T1 breast cancer murine model. MTT, live and dead cell staining, apoptosis, ROS generation, and clonogenic in vitro assays demonstrated the efficacy of NPs as radiosensitizers in radiotherapy. In vivo results as well as H&E staining tumor tissues confirmed tumor destruction in the group that received Ag-Ag2S@BSA-FA NPs and exposed to X-ray. The results showed that prepared tumor-targeted Ag-Ag2S@BSA-FA NPs could be potential candidates as radiosensitizers for enhanced radiotherapy.

Artificial Intelligence in Regenerative Medicine: Applications and Implications.

The field of regenerative medicine is constantly advancing and aims to repair, regenerate, or substitute impaired or unhealthy tissues and organs using cutting-edge approaches such as stem cell-based therapies, gene therapy, and tissue engineering. Nevertheless, incorporating artificial intelligence (AI) technologies has opened new doors for research in this field. AI refers to the ability of machines to perform tasks that typically require human intelligence in ways such as learning the patterns in the data and applying that to the new data without being explicitly programmed. AI has the potential to improve and accelerate various aspects of regenerative medicine research and development, particularly, although not exclusively, when complex patterns are involved. This review paper provides an overview of AI in the context of regenerative medicine, discusses its potential applications with a focus on personalized medicine, and highlights the challenges and opportunities in this field.

Magnetic ferrite nanoparticles coated with bovine serum albumin and glycine polymers for controlled release of curcumin as a model.

To conquer the low water solubility and bioavailability of curcumin (CUR), to corroborate its functional qualities and to broaden its applicability in the pharmaceutical sector, numerous nanoscale methods have been widely exploited for its administration. Because of its polycystic, biodegradable, biocompatibility, non-toxicity, and non-allergenic properties, bovine serum albumin (BSA) and glycine (Gly) have been actively investigated as natural biopolymers for decades. Various BSA and Gly-based nanocarriers with unique features for CUR delivery, such as magnetic ferrite nanoparticles, are being developed (MNPs). In this work, magnesium ferrite (MgFe2O4)/BSA and nickel ferrite (NiFe2O4)/Gly nanocomposites loaded with CUR (drug model) were manufactured for the first time using a chemical co-precipitation approach to create biocompatible drug nanocarriers. It was found that the synthesized MgFe2O4/BSA and NiFe2O4/Gly nanoparticles have a uniform particle distribution and their size is much less than 100 nm. Saturation magnetization in MgFe2O4 and NiFe2O4 reaches 13.07 and 33.4 emu/g the remarkable peak of magnetization decreases to 10.99 and 32.36 emu/g after the addition of polymers. These analyses also showed the presence of chemical bonds in the structure of the nanocomposite. The curcumin diffusion process in NPs were determined using a mathematical modeling. The yielding of the product for MgFe2O4/BSA and NiFe2O4/Gly in 200 h is about 72 and 63%, respectively. Also, regressed relative diffusivities (D/R2), including effective steric hindrance, were determined as 5.75 × 10-4 and 2.72 × 10-4 h-1 for MgFe2O4/BSA and NiFe2O4/Gly, respectively. It shows that there is a significant steric barrier that significantly deviates from the molecular diffusion of the liquid. As a result, the low effective release of curcumin in the particles is more noticeable. Our study demonstrated the effective relationship between the polymer architecture and the biophysical properties of the resulting nanoparticles and shed light on new approaches for the design of efficient NP-based drug carriers.

Synthesis of Pt nanoparticles with gelatin-assisted green route to improve sensitization of cancer cells to X-Ray irradiation.

This study aimed to develop a novel radiosensitizer consisting of platinum nanoparticles (Pt NPs) as a high-atomic-number element in order to maximize the generation of ROS under ionizing radiation at the tumor site. Pt NPs were produced via a green and facile method in the presence of gelatin (Gel) as both reducing and stabilizing agent. After determining the physical structure and chemical composition of Pt@Gel NPs by STEM, FeSEM, EDS, DLS, XRD and FTIR, in vitro cytotoxicity on human umbilical vein endothelial cells (HUVEC) and breast cancer cell line (4T1) was evaluated by MTT assay. Finally, ROS generation assay, calcein AM/PI staining assay and clonogenic test were performed on 4T1 cells under X-Ray irradiation to evaluate the radioenhancment efficiency of Pt@Gel. The prepared NPs exhibited spherical and uniform shapes and narrowly distributed sizes in addition to an acceptable radiosensitization capability. The nanosystem provided higher levels of intracellular ROS in malignant cells and enhanced cancer cell death rate under X-Ray irradiation. Overall, the findings suggested that Pt@Gel could be a safe and effective alternative to existing radiosensitizers and potentially be employed for the treatment of breast cancer.

Silver sulfide coated alginate radioenhancer for enhanced X-ray radiation therapy of breast cancer.

A wide range of high-Z nanomaterials are fabricated to decrease radiation dose by sensitizing cells to irradiation through various mechanisms such as ROS generation enhancement. Alginate-coated silver sulfide nanoparticles (Ag2S@Alg) were synthesized and characterized by SEM, TEM, DLS, XRD, EPS, FT-IR, and UV-vis analysis techniques. Cytotoxicity of nanoparticles was tested against HFF-2, MCF-7, and 4 T1 cell lines for biocompatibility and radio enhancement ability evaluation, respectively. Moreover, the hemolysis assay demonstrated that the nanoparticles were biocompatible and nontoxic. In vitro intracellular ROS generation and calcein AM/PI co-staining unveiled cancerous cell death induction by nanoradiosensitizer, Ag2S@Alg. Further, histopathology results emphasized the tumor ablation capability of Ag2S@Alg. Silver anticancer properties were also recognized and combined with its radiosensitizing effect under X-ray irradiation.

Preparation of alginate coated Pt nanoparticle for radiosensitization of breast cancer tumor.

Noble metals as high atomic number elements can localize X-ray radiation within tumor cells by exploiting different mechanisms. Here, alginate (Alg)-coated platinum nanoparticles (Pt@Alg) were synthesized, characterized, and implemented as a radiosensitizer to enhance X-ray therapeutic efficacy in breast cancer in vitro and in vivo. Alg not only improves the biocompatibility of the radioenhancer, but also stabilizes the nanoparticles. Pt@Alg was studied by different characterization methods including DLS, STEM, Fe-SEM, XRD, XPS, FT-IR and UV-Vis spectrophotometry. The nanosystem provided a higher level of intracellular ROS in malignant cells and enhanced cancer cell death under X-Ray irradiation. Clonogenic assay also demonstrated the radiosensitizing properties of the nanosystem, in vitro. In vivo result show tumor growth restraining properties of the nanosystem when it was administrated along with X-Ray irradiation. Histopathology results confirmed the impact of nanosystem and X-ray co-treatment, as well. Altogether, the importance of radiosensitizers for improving radiotherapy outcomes was highlighted.

Enhanced In Vivo Radiotherapy of Breast Cancer Using Gadolinium Oxide and Gold Hybrid Nanoparticles.

Radiation therapy has demonstrated promising effectiveness against several types of cancers. X-ray radiation therapy can be made further effective by utilizing nanoparticles of high-atomic-number (high-Z) materials that act as radiosensitizers. Here, in purpose of maximizing the radiation therapy within tumors, bovine serum albumin capped gadolinium oxide and gold nanoparticles (Gd2O3@BSA-Au NPs) are developed as a bimetallic radiosensitizer. In this study, we incorporate two high-Z-based nanoparticles, Au and Gd, in a single nanoplatform. The radiosensitizing ability of the nanoparticles was assessed with a series of in vitro tests, following evaluation in vivo in a breast cancer murine model. Enhanced tumor suppression is observed in the group that received radiation after administration of Gd2O3@BSA-Au NPs. As a result, cancer therapy efficacy is significantly improved by applying Gd2O3@BSA-Au NPs under X-ray irradiation, as evidenced by studies evaluating cell viability, proliferation, reactive oxygen species production, and in vivo anti-tumor effect.

Targeted CuFe2O4 hybrid nanoradiosensitizers for synchronous chemoradiotherapy.

Multifunctional nanoplatforms based on novel bimetallic nanoparticles have emerged as effective radiosensitizers owing to their potential capability in cancer cells radiosensitization. Implementation of chemotherapy along with radiotherapy, known as synchronous chemoradiotherapy, can augment the treatment efficacy. Herein, a tumor targeted nanoradiosensitizer with synchronous chemoradiotion properties, termed as CuFe2O4@BSA-FA-CUR, loaded with curcumin (CUR) and modified by bovine serum albumin (BSA) and folic acid (FA) was developed to enhance tumor accumulation and promote the anti-cancer activity while attenuating adverse effects. Both copper (Cu) and iron (Fe) were utilized in the construction of these submicron scale entities, therefore strong radiosensitization effect is anticipated by implementation of these two metals. The structure-function relationships between constituents of nanomaterials and their function led to the development of nanoscale materials with great radiosensitizing capacity and biosafety. BSA was used to anchor Fe and Cu ions but also to improve colloidal stability, blood circulation time, biocompatibility, and further functionalization. Moreover, to specifically target tumor sites and enhance cellular uptake, FA was conjugated onto the surface of hybrid bimetallic nanoparticles. Finally, CUR as a natural chemotherapeutic agent was encapsulated into the developed bimetallic nanoparticles. With incorporation of all abovementioned stages into one multifunctional nanoplatform, CuFe2O4@BSA-FA-CUR is produced for synergistic chemoradiotherapy with positive outcomes. In vitro investigation revealed that these nanoplatforms bear excellent biosafety, great tumor cell killing ability and radiosensitizing capacity. In addition, high cancer-suppression efficiency was observed through in vivo studies. It is worth mentioning that co-use of CuFe2O4@BSA-FA-CUR nanoplatforms and X-ray radiation led to complete tumor ablation in almost all of the treated mice. No mortality or radiation-induced normal tissue toxicity were observed following administration of CuFe2O4@BSA-FA-CUR nanoparticles which highlights the biosafety of these submicron scale entities. These results offer powerful evidence for the potential capability of CuFe2O4@BSA-FA-CUR in radiosensitization of malignant tumors and opens up a new avenue of research in this area.

UV-Cured Green Polymers for Biosensorics: Correlation of Operational Parameters of Highly Sensitive Biosensors with Nano-Volumes and Adsorption Properties.

The investigated polymeric matrixes consisted of epoxidized linseed oil (ELO), acrylated epoxidized soybean oil (AESO), trimethylolpropane triglycidyl ether (RD1), vanillin dimethacrylate (VDM), triarylsulfonium hexafluorophosphate salts (PI), and 2,2-dimethoxy-2-phenylacetophenone (DMPA). Linseed oil-based (ELO/PI, ELO/10RD1/PI) and soybean oil-based (AESO/VDM, AESO/VDM/DMPA) polymers were obtained by cationic and radical photopolymerization reactions, respectively. In order to improve the cross-linking density of the resulting polymers, 10 mol.% of RD1 was used as a reactive diluent in the cationic photopolymerization of ELO. In parallel, VDM was used as a plasticizer in AESO radical photopolymerization reactions. Positron annihilation lifetime spectroscopy (PALS) was used to characterize vegetable oil-based UV-cured polymers regarding their structural stability in a wide range of temperatures (120-320 K) and humidity. The polymers were used as laccase immobilization matrixes for the construction of amperometric biosensors. A direct dependence of the main operational parameters of the biosensors and microscopical characteristics of polymer matrixes (mostly on the size of free volumes and water content) was established. The biosensors are intended for the detection of trace water pollution with xenobiotics, carcinogenic substances with a very negative impact on human health. These findings will allow better predictions for novel polymers as immobilization matrixes for biosensing or biotechnology applications.

Magnetite and bismuth sulfide Janus heterostructures as radiosensitizers for in vivo enhanced radiotherapy in breast cancer.

Janus heterostructures based on bimetallic nanoparticles have emerged as effective radiosensitizers owing to their radiosensitization capabilities in cancer cells. In this context, this study aims at developing a novel bimetallic nanoradiosensitizer, Bi2S3-Fe3O4, to enhance tumor accumulation and promote radiation-induced DNA damage while reducing adverse effects. Due to the presence of both iron oxide and bismuth sulfide metallic nanoparticles in these newly developed nanoparticle, strong radiosensitizing capacity is anticipated through the generation of reactive oxygen species (ROS) to induce DNA damage under X-Ray irradiation. To improve blood circulation time, biocompatibility, colloidal stability, and tuning surface functionalization, the surface of Bi2S3-Fe3O4 bimetallic nanoparticles was coated with bovine serum albumin (BSA). Moreover, to achieve higher cellular uptake and efficient tumor site specificity, folic acid (FA) as a targeting moiety was conjugated onto the bimetallic nanoparticles, termed Bi2S3@BSA-Fe3O4-FA. Biocompatibility, safety, radiation-induced DNA damage by ROS activation and generation, and radiosensitizing ability were confirmed via in vitro and in vivo assays. The administration of Bi2S3@BSA-Fe3O4-FA in 4T1 breast cancer murine model upon X-ray radiation revealed highly effective tumor eradication without causing any mortality or severe toxicity in healthy tissues. These findings offer compelling evidence for the potential capability of Bi2S3@BSA-Fe3O4-FA as an ideal nanoparticle for radiation-induced cancer therapy and open interesting avenues of future research in this area.

BSA-PEI Nanoparticle Mediated Efficient Delivery of CRISPR/Cas9 into MDA-MB-231 Cells.

The discovery of bacterial-derived Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has revolutionized genome engineering and gene therapy due to its wide range of applications. One of the major challenging issues in CRISPR/Cas system is the lack of an efficient, safe, and clinically suitable delivery of the system's components into target cells. Here, we describe the development of polyethylenimine coated-bovine serum albumin nanoparticles (BSA-PEI NPs) for efficient delivery of CRISPR/Cas9 system in both DNA (px458 plasmid) and ribonucleoprotein (RNP) forms into MDA-MB-231 human breast cancer cell line. Our data showed that synthesized BSA-PEI (BP) NPs delivered plasmid px458 at concentrations of 0.15, 0.25, and 0.35 µg/µl with efficiencies of approximately 29.7, 54.8, and 84.1% into MDA-MB-231 cells, respectively. Our study demonstrated that Cas9/sgRNA RNP complex efficiently (~ 92.6%) delivered by BSA-PEI NPs into the same cells. Analysis of toxicity and biocompatibility of synthesized NPs on human red blood cells, MDA-MB-231 cells, and mice showed that the selected concentration (28 µg/µl) of BSA-PEI NPs for transfection had no remarkable toxicity effects. Thus, obtained results suggest BSA-PEI NPs as one of the most promising carrier for delivering CRISPR/Cas9 to target cells.

Electrosprayed cefazolin-loaded niosomes onto electrospun chitosan nanofibrous membrane for wound healing applications.

Chronic wounds are among the most therapeutically challenging conditions, which are commonly followed by bacterial infection. The ideal approach to treat such injuries are synergistic infection therapy and skin tissue regeneration. In the recent decades, nanotechnology has played a critical role in eradicating bacterial infections by introducing several carriers developed for drug delivery. Moreover, advances in tissue engineering have resulted in new drug delivery systems that can improve the skin regeneration rate and quality. In this study, cefazolin-loaded niosomes were electrosprayed onto chitosan membrane for wound healing applications. For this purpose, niosomes were obtained by the thin-film hydration method; electrospinning was then conducted to fabricate nanofibrous mats. In vitro characterization of the scaffold was performed to evaluate the physicochemical and biological properties. Finally, in vivo studies were carried out to evaluate the potential use of the membrane for skin regeneration. In vitro results indicated the antibacterial properties of the membrane against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) due to the gradual release of cefazolin from niosomes. The scaffolds also showed no cell toxicity. In vivo studies also confirmed the ability of the membrane to enhance skin regeneration by improving re-epithelialization, tissue remodeling, and angiogenesis. The current study could well show the promising role of the prepared scaffold for skin regeneration and bacterial infection elimination.

Curcumin delivery by modified biosourced carbon-based nanoparticles.

Aim: To prepare a novel hybrid system for the controlled release and delivery of curcumin (CUR). Methods: A method for the ultrasound-assisted fabrication of protein-modified nanosized graphene oxide-like carbon-based nanoparticles (CBNPs) was developed. After being modified with bovine serum albumin (BSA), CUR was loaded onto the synthesized hybrid (labeled CBNPs@BSA-CUR). The structure and properties of the synthesized nanoparticles were elucidated using transmission electron microscopy (TEM), atomic force microscopy (AFM), ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR) and x-ray photoelectron spectroscopy (XPS) methods. Results: CBNPs@BSA-CUR showed pH sensitivity and were calculated as controlled CUR release behavior. The drug-free system exhibited good biocompatibility and was nontoxic. However, CBNPs@BSA-CUR showed acceptable antiproliferative ability against MCF-7 breast cancer cells. Conclusion: CBNPs@BSA-CUR could be considered a highly promising nontoxic nanocarrier for the delivery of CUR with good biosafety.

Anticancer evaluation of methotrexate and curcumin-coencapsulated niosomes against colorectal cancer cell lines.

Aim: The aim of the present investigation was to develop niosomes containing both curcumin (CUR) and methotrexate (MTX). Also, the combinational effect of CUR and MTX in both free and niosomal forms on growth inhibition potential and induction of apoptosis in the HCT-116 cell line were exploited. Materials & methods: Niosomes were prepared by the thin-film hydration method and their physicochemical properties were determined by various techniques. Cellular uptake, cell apoptosis, wound healing and MTT assay were conducted to ascertain niosomes' feasibility for cancer therapy. Results: The combination of CUR and MTX in niosomal formulation showed more toxicity than their combination in free form. Conclusion: The nanocarrier-based approach was effective for the codelivery of CUR and MTX against cancer cells in vitro.

Prodrug Polymeric Nanoconjugates Encapsulating Gold Nanoparticles for Enhanced X-Ray Radiation Therapy in Breast Cancer.

An optimal radiosensitizer with improved tumor retention has an important effect on tumor radiation therapy. Herein, gold nanoparticles (Au NPs) and drug-containing, mPEG-conjugated CUR (mPEG-CUR), self-assembled NPs (mPEG-CUR@Au) are developed and evaluated as a drug carrier and radiosensitizer in a breast cancer mice model. As a result, cancer therapy efficacy is improved significantly by applying all-in-one NPs to achieve synchronous chemoradiotherapy, as evidenced by studies evaluating cell viability, proliferation, and ROS production. In vivo anticancer experiments show that the mPEG-CUR@Au system improves the radiation sensitivity of 4T1 mammary carcinoma and completely abrogates breast cancer.

Complete ablation of tumors using synchronous chemoradiation with bimetallic theranostic nanoparticles.

Synchronous chemotherapy and radiotherapy, termed chemoradiation therapy, is now an important standard regime for synergistic cancer treatment. For such treatment, nanoparticles can serve as improved carriers of chemotherapeutics into tumors and as better radiosensitizers for localized radiotherapy. Herein, we designed a Schottky-type theranostic heterostructure, Bi2S3-Au, with deep level defects (DLDs) in Bi2S3 as a nano-radiosensitizer and CT imaging contrast agent which can generate reactive free radicals to initiate DNA damage within tumor cells under X-ray irradiation. Methotrexate (MTX) was conjugated onto the Bi2S3-Au nanoparticles as a chemotherapeutic agent showing enzymatic stimuli-responsive release behavior. The designed hybrid system also contained curcumin (CUR), which cannot only serve as a nutritional supplement for chemotherapy, but also can play an important role in the radioprotection of normal cells. Impressively, this combined one-dose chemoradiation therapeutic injection of co-drug loaded bimetallic multifunctional theranostic nanoparticles with a one-time clinical X-ray irradiation, completely eradicated tumors in mice after approximately 20 days after irradiation showing extremely effective anticancer efficacy which should be further studied for numerous anti-cancer applications.

Cationic, anionic and neutral polysaccharides for skin tissue engineering and wound healing applications.

Today, chronic wound care and management can be regarded as a clinically critical issue. However, the limitations of current approaches for wound healing have encouraged researchers and physicians to develop more efficient alternative approaches. Advances in tissue engineering and regenerative medicine have resulted in the development of promising approaches that can accelerate wound healing and improve the skin regeneration rate and quality. The design and fabrication of scaffolds that can address the multifactorial nature of chronic wound occurrence and provide support for the healing process can be considered an important area requiring improvement. In this regard, polysaccharide-based scaffolds have distinctive properties such as biocompatibility, biodegradability, high water retention capacity and nontoxicity, making them ideal for wound healing applications. Their tunable structure and networked morphology could facilitate a number of functions, such as controlling their diffusion, maintaining wound moisture, absorbing a large amount of exudates and facilitating gas exchange. In this review, the wound healing process and the influential factors, structure and properties of carbohydrate polymers, physical and chemical crosslinking of polysaccharides, scaffold fabrication techniques, and the use of polysaccharide-based scaffolds in skin tissue engineering and wound healing applications are discussed.

The potential renal toxicity of silver nanoparticles after repeated oral exposure and its underlying mechanisms.

BACKGROUND: Silver nanoparticles (AgNPs) can accumulate in various organs after oral exposure. The main objective of the current study is to evaluate the renal toxicity induced by AgNPs after repeated oral exposure and to determine the relevant molecular mechanisms. METHODS: In this study, 40 male Wistar rats were treated with solutions containing 30, 125, 300, and 700 mg/kg of AgNPs. After 28 days of exposure, histopathological changes were assessed using hematoxylin-eosin (H&E), Masson's trichrome, and periodic acid-Schiff (PAS) staining. Apoptosis was quantified by TUNEL and immunohistochemistry of caspase-3, and the level of expression of the mRNAs of growth factors was determined using RT-PCR. RESULTS: Histopathologic examination revealed degenerative changes in the glomeruli, loss of tubular architecture, loss of brush border, and interrupted tubular basal laminae. These changes were more noticeable in groups treated with 30 and 125 mg/kg. The collagen intensity increased in the group treated with 30 mg/kg in both the cortex and the medulla. Apoptosis was much more evident in middle-dose groups (i.e., 125 and 300 mg/kg). The results of RT-PCR indicated that Bcl-2 and Bax mRNAs upregulated in the treated groups (p < 0.05). Moreover, the data related to EGF, TNF-α, and TGF-ß1 revealed that AgNPs induced significant changes in gene expression in the groups treated with 30 and 700 mg/kg compared to the control group. CONCLUSION: Our observations showed that AgNPs played a critical role in in vivo renal toxicity.

Iron oxide and gold bimetallic radiosensitizers for synchronous tumor chemoradiation therapy in 4T1 breast cancer murine model.

The development of highly integrated multifunctional nanomaterials with a superadditive therapeutic effect and good safety is an urgent but challenging task in cancer therapy research. The present study aims to design a nanoplatform that offers the opportunity to enhance antitumor activity while minimizing side effects. Given the Au-mediated X-ray radiation enhancement and the ability of Fe-based nanomaterials to create reactive oxygen species (ROS) and DNA damage, we anticipated that bimetallic Fe3O4-Au heterodimer would bring strong radiosensitizing capacity. Fe3O4-Au heterodimer surface was covered with bovine serum albumin (BSA) to achieve good surface functionality, stability and prolonged blood circulation. Folic acid (FA) moieties were added to the nanoformulation to increase tumor-homing, specificity and uptake. Finally, curcumin (CUR) was incorporated into the nanoparticle to function as a natural anticancer agent. The integration of all these components has yielded a single nanoplatform, Fe3O4-Au-BSA-FA-CUR, capable of successfully fulfilling the mission of superadditive cancer therapy to avoid the risks of organ removal surgery. The efficacy of the proposed nanoplatform was investigated in vitro and in vivo. High radiosensitizing ability, X-ray-induced ROS generation and DNA damage, and good biocompatibility were demonstrated through in vitro experiments. Also, the administration of Fe3O4-Au-BSA-FA-CUR with X-ray irradiation completely eradicated the tumor without any mortality and toxicity in healthy tissues in vivo. Our results highlight the potential of CUR-loaded Fe3O4-Au-BSA-FA heteronanostructure to enable synergistic localized radiochemotherapy and open up a new door to attractive possibilities that warrant further exploration.