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.

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.

Synthesis of Fe3O4-Gold hybrid nanoparticles coated by bovine serum albumin as a contrast agent in MR imaging.

Despite the over spatial separation and the ability to determine soft tissues, insufficient contrast is the shortcoming of magnetic resonance imaging (MRI) that could be circumvented by the use of contrast agents. The use of MRI contrast agents are widely applied to enhance the vision of internal body structures. Nano-sized contrast materials have unique application advantages compared to other contrast agents due to their size and shape. However, for contrast agents such as bare iron (II, III) oxide (Fe3O4) magnetic nanoparticles (NPs), aggregation and accumulation are the main shortcomings. Thus, surface modifications are necessary for their use in biopharmaceutical applications. Gold, Au, nanoparticles are of big interesting for use in biomedical purposes due to their chemical stability and oxidation resistance. In this study, we synthesized magnetic Fe3O4-Au hybrid NPs with a facile method and coated them with bovine serum albumin (BSA) to increase their chemical stability and biocompatibility. Afterwards, the hybrid nanosystem was characterized by some methods, and their potential to increase MRI contrast was investigated by the phantom MRI experiments. Our data showed that the signal intensity on MR images was significantly reduced, thus confirming the contrast ability of the formulated Fe3O4-Au-BSA NPs.

Folic acid-modified biocompatible Pullulan/poly(acrylic acid) nanogels for targeted delivery to MCF-7 cancer cells.

We prepared a novel nanogel consisting of poly(acrylic acid) (PAA) and pullulan (Pull) via a facile and green irradiation protocol. Synthesized nanogels were modified with bovine serum albumin (BSA) and folic acid (FA) and then loaded with doxorubicin (DOX) to obtain a delivery system with tumor-specific targeting ability and enhanced biocompatibility. In-vitro DOX release was investigated at different pH values, and it was found that DOX release was higher in acidic media, which is an advantage for the internalization of nanoparticles in acidic tumor environment. MTT assay and DAPI staining were performed to evaluate the effects of nanogels on L929 and MCF-7 cells. Based on the results of in vitro studies, DOX-loaded nanogels were found to be effective on cancer cells, while the neat ones were nondestructive in both lines. Overall, we envision that the biocompatible and tumor-specific nanogels could be a promising safe drug carrier system for cancer therapy.

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.

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.

Green and Facile Synthesis of Pullulan-Stabilized Silver and Gold Nanoparticles for the Inhibition of Quorum Sensing.

Pullulan (Pull) decorated with monodisperse Ag and Au nanoparticles (NPs) was synthesized by a simple and green method. Samples were characterized by FTIR, UV-vis, NMR, XRD, TGA, SEM, XPS, DLS, and TEM. SEM images showed highly oriented microforms reported for the first time for Pull, because of the supramolecular self-assembling behavior of Pull chains. Antimicrobial and quorum sensing (QS) inhibition activities were tested against six pathogen bacteria and reporter and biomonitor strain. Pull decorated with NPs, in particular, Ag-modified ones, outperformed pristine Pull. The cell proliferation was tested with an MTT assay. NPs-decorated Pull was studied for the first time as an inhibitory agent against bacterial signal molecules and found to be a good candidate. The promising performance of AgNPs@Pull compared to the commercial antibiotic gentamicin showed that it has great potential as a therapeutic approach to overcome the bacterial resistance that has developed against conventional antibiotics.

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.

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.

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.

Bovine serum albumin-mediated synthesis and quorum sensing inhibitory properties of Ag-Ag2S nanoparticles.

Aim: Quorum sensing (QS) is a density-dependent chemical process of cell-to-cell communication in which certain signals are activated, leading to the coordination of pathogenic behaviors and the regulation of virulence in bacteria. Inhibition of QS can prevent biofilm formation and reduce virulence behaviors of bacteria. Herein, bovine serum albumin (BSA)-coated silver nanoparticles (NPs) (Ag-Ag2S@BSA NPs) were synthesized and studied as an anti-QS agent. Materials & methods: Ag-Ag2S NPs prepared through a BSA-mediated biomineralization process under ambient aqueous conditions and their physicochemical properties were characterized. The anti-QS activity of the resulting BSA-coated NPs (Ag-Ag2S@BSA NPs) was investigated for the first time. Results & conclusion: The result confirmed the potential of Ag-Ag2S@BSA NPs as novel and useful therapeutic tools for antibacterial purposes.

The overuse of antibiotics has caused the development of drug-resistant strains of bacteria. Nowadays, drug resistance is one of the main challenges in the treatment and prevention of microbial diseases. In general, many bacterial species communicate with each other through a population-dependent mechanism called quorum sensing to control their physiological activities. Therefore, inhibiting the quorum sensing mechanism is an attractive alternative to antibiotics and also reduces the risk of drug resistance, and this can be achieved by nanoparticles (NPs). Among these nanostructures, Ag NPs have received particular attention due to their antimicrobial, antibiofilm, anticancer and antioxidant properties. Herein, we report a method that applies a BSA-guided green and one-pot approach for achieving Ag­Ag₂S NPs as potential antibacterial agents.

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.

CRISPR Systems for COVID-19 Diagnosis.

The emergence of the new coronavirus 2019 (COVID-19) was first seen in December 2019, which has spread rapidly and become a global pandemic. The number of cases of COVID-19 and its associated mortality have raised serious concerns worldwide. Early diagnosis of viral infection undoubtedly allows rapid intervention, disease management, and substantial control of the rapid spread of the disease. Currently, the standard approach for COVID-19 diagnosis globally is the RT-qPCR test; however, the limited access to kits and associated reagents, the need for specialized lab equipment, and the need for highly skilled personnel has led to a detection slowdown. Recently, the development of clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostic systems has reshaped molecular diagnosis. The benefits of the CRISPR system such as speed, precision, specificity, strength, efficiency, and versatility have inspired researchers to develop CRISPR-based diagnostic and therapeutic methods. With the global COVID-19 outbreak, different groups have begun to design and develop diagnostic and therapeutic programs based on the efficient CRISPR system. CRISPR-based COVID-19 diagnostic systems have advantages such as a high detection speed (i.e., 30 min from raw sample to reach a result), high sensitivity and precision, portability, and no need for specialized laboratory equipment. Here, we review contemporary studies on the detection of COVID-19 based on the CRISPR system.