Prodrug polymeric nanoconjugates encapsulating gold nanoparticles for enhanced X-Ray radiation therapy in breast cancer

This work was supported by the Deputy of Research of Zanjan University of Medical Sciences (A-12-848-30). J.C. acknowledges financial support from the European Research Council – ERC Starting Grant 848325.An optimal radiosensitizer with improved tumor retention have an important effect in tumor radiation therapy. Herein, gold nanoparticles (Au NPs) and drug containing, mPEG-conjugated CUR (mPEG-CUR), self-assembled NPs (mPEG-CUR@Au) were developed and evaluated as a drug carrier and radiosensitizer in a breast cancer mice model. As a result, cancer therapy efficacy was 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 showed that the mPEG-CUR@Au system improves the radiation sensitivity of 4T1 mammary carcinoma and completely abrogates breast cancer. This article is protected by copyright. All rights reserved.publishersversionpublishe

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 RTqPCR 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 CRISPRbased 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

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

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

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

© 2023Noble 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

Preparation and evaluation of bismuth sulfide and magnetite-based theranostic nanohybrid as drug carrier and dual MRI/CT contrast agent

Due to the increased incidence and population growth that has been leading to growing number of cases worldwide, early diagnosis and treatment of cancer is crucial. Low density cancer tissue cannot be diagnosed before progressing toward a metastatic stage. Thus, theranostic systems play a significant role in assisting timely diagnosis and treatment. The combination of magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents in a single probe is of high importance and necessity, where individual strengths of each approach can be merged while shortcomings of each modality could be compensated. With this motivation, we have developed and synthesized Bi2S3@BSA-Fe3O4 nanoparticles as a dual MRI/CT contrast agent and carrier of curcumin (CUR) as natural anticancer drug. The nanoparticles shortened both the longitudinal (T-1) and transverse (T-2), MRI relaxation times, with a more distinct effect on producing negative contrast (T-2) images with a relaxivity (r(2)) of 54.73 mM(-1) s(-1). The magnetite/bismuth hybrid nanoparticle also was capable of increasing CT image contrast. Further, in vitro cytotoxicity assay showed high biocompatibility of the synthesized nanoparticles. Furthermore, in vitro cytotoxicity assay on cancer cells showed high anticancer activity of the synthesized nanoparticles

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

Abstract 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

Chemoradiation therapy of 4T1 cancer cells with methotrexate conjugated platinum nanoparticles under X-Ray irradiation

© 2023 Elsevier B.V.Bovine serum albumin (BSA) coated platinum (Pt) nanoparticles (Pt@BSA NPs) were synthesized, followed by the conjugation of an anticancer drug (MTX) with the aim of chemoradiation therapy. The physical and chemical properties of Pt@BSA-MTX were evaluated by DLS, FESEM, STEM, UV–Vis and XRD. A release study was performed in the presence and absence of the proteinase K enzyme. In terms of morphology, nanoparticles appeared to be monodispersed and spherical. The size of nanoparticles was 7.4 ± 1.4 nm. Release behavior of Pt@BSA-MTX depended significantly on enzyme presence which accelerated and promoted the release of MTX. The improved chemoradiation was demonstrated in vitro using MTT, colony formation and apoptosis assays on mouse breast carcinoma cells (4T1). It was concluded that the combination of a nanoradiosensitizer with a chemotherapeutic agent resulted in superior anticancer activity after X-ray exposure

Targeted CuFe2O4 hybrid nanoradiosensitizers for synchronous chemoradiotherapy

© 2022 Elsevier B.V.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 bime-tallic 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