Methotrexate-conjugated L-lysine coated iron oxide magnetic nanoparticles for inhibition of MCF-7 breast cancer cells.

Methotrexate (MTX), a stoichiometric inhibitor of dihydrofolate reductase enzyme, is a chemotherapeutic agent for treating a diversity of neoplasms. In this study, we design and developed a new formulation of MTX that serves as drug carrier and examined its cytotoxic effect in vitro. This target drug delivery system is dependent on the release of the MTX within the lysosomal compartment. The iron oxide magnetic nanoparticles (IONPs) were first surface-coated with L-lysine and subsequently conjugated with MTX through amidation between the carboxylic acid end groups on MTX and the amine groups on the IONPs surface. MTX-conjugated L-lysine coated IONPs (F-Lys-MTX NPs) was characterized by X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, vibrating sample magnetometer, and transmission electron microscopy techniques. The cytotoxicity of the void of MTX and F-Lys-MTX NPs were compared to each other by MTT assay of the treated MCF-7 cell lines. The results showed that the ζ-potential of F-Lys-MTX NPs was about -5.49 mV and the average size was 43.72 ± 4.73 nm. Model studies exhibited the release of MTX via peptide bond cleavage in the presence of proteinase K and at low pH. These studies specify that F-Lys-MTX NPs have a very remarkable anticancer effect, for breast cancer cell lines.

Theranostic nanoparticles based on magnetic nanoparticles: design, preparation, characterization, and evaluation as novel anticancer drug carrier and MRI contrast agent.

In this work, we reported the synthesis of curcumin (CUR)-loaded hydrophilic and hydrophobic natural amino acids (AAs)-modified iron oxide magnetic nanoparticles (IONPs). Two types of AAs, l-lysine (Lys) and l-phenylalanine (PhA), were selected to study their effects on loading capacity, release profile of CUR, biocompatibility, and anticancer activity. CUR-loaded AAs-modified IONPs (F@AAs@CUR NPs) were characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM), and transmission electron microscopy (TEM) techniques. Next, the various kinetic equations were fitted to the release data of CUR from F@Lys@CUR NPs and F@PhA@CUR NPs. Additionally, hemolysis test and MTT assays on HFF-2 and HEK-293 cell lines were performed for determination of biocompatibility of AAs-coated IONPs. Finally, the anticancer activity of F@AAs@CUR NPs examined on MCF-7 breast cancer cell line. The results indicate that these nanocarriers are nontoxic and biocompatible and also F@AAs@CUR NPs are suitable carriers for delivery of curcumin and even other hydrophobic drugs. Also, the MRI training established the effectiveness of IONPs as contrast agent for the revealing of tumor as evidenced from the phantom images as well as higher T2 relaxivity.

Preparation, characterization, and evaluation of amino acid modified magnetic nanoparticles: drug delivery and MRI contrast agent applications.

This study is a report about the synthesis iron oxide magnetic nanoparticles (IONPs) which modified with positive and negative charged amino acids (AAs). l-Arginine (Arg) and l-aspartic acid (Asp) which have of guanidinium and carboxylic acid groups, respectively, were selected for this study. After loading chrysin in amino acids modified iron oxide magnetic nanoparticles (F@AAs@Chrysin NPs), it was characterized by XRD, TGA, FTIR, VSM, and TEM techniques. Finally, MTT assays on HFF-2 and HEK-293 cell lines were performed for determination of biocompatibility of AA coated IONPs. The results show that, the ζ-potential and average size of F@Arg@chrysin NPs and F@Asp@chrysin NPs were to -3.87, -2.12 mV, 18.75 ± 2.40 (mean ± SD (n = 50)) nm, and 19.86 ± 2.22 (mean ± SD (n = 48)) nm, respectively. Also, the results indicated that these F@AAs@Chrysin NPs were appropriate for delivery of chrysin. Furthermore, the phantom MRI studies showed the IONPs can be used as contrast agent for the revealing of tumor.

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.

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.

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.

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.

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.

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.

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.

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.

Nanotechnology against the novel coronavirus (severe acute respiratory syndrome coronavirus 2): diagnosis, treatment, therapy and future perspectives.

COVID-19, as an emerging infectious disease, has caused significant mortality and morbidity along with socioeconomic impact. No effective treatment or vaccine has been approved yet for this pandemic disease. Cutting-edge tools, especially nanotechnology, should be strongly considered to tackle this virus. This review aims to propose several strategies to design and fabricate effective diagnostic and therapeutic agents against COVID-19 by the aid of nanotechnology. Polymeric, inorganic self-assembling materials and peptide-based nanoparticles are promising tools for battling COVID-19 as well as its rapid diagnosis. This review summarizes all of the exciting advances nanomaterials are making toward COVID-19 prevention, diagnosis and therapy.

Tumor Targeted Albumin Coated Bismuth Sulfide Nanoparticles (Bi2S3) as Radiosensitizers and Carriers of Curcumin for Enhanced Chemoradiation Therapy.

Combination therapy such as radiotherapy combined with chemotherapy has attracted excessive interest in the new cancer research area. Therefore, developing nanobiomaterials for combination of radiotherapy and chemotherapy is required for more powerful and successful cures. Because of the amazing X-ray sensitization proficiency of Bi based nanoparticles, in this work, we synthesized and used Bi2S3 as an enhancer of X-ray radiation therapy, and furthermore, Bi2S3 served as carrier of curcumin (CUR), a chemotherapy drug, for the goal of combination therapy. Additionally, we selected and conjugated folic acid (FA) as a targeting molecule for the direction of the designed system to the tumor site. After characterization of drug loaded FA conjugated Bi2S3@BSA nanoparticles (Bi2S3@BSA-FA-CUR) and in vitro and in vivo safety assessment, we applied it for enhanced chemotherapy and X-ray radiation therapy in cancer cells and a tumor bearing mice model. Moreover, the CT contrast ability of synthesized nanoparticles was examined. Here, we (1) for the first time developed the novel and targeted CUR loaded Bi2S3@BSA (Bi2S3@BSA-FA-CUR) to promote chemoradiation therapy in 4T1 cells and breast tumor in mice; (2) found the synthesized nanoparticles to have good stability; (3) injected a single dose of the designed radiosensitizer for cancer therapy; and (4) used a conventional X-ray dose, 2Gy, for X-ray radiation therapy. The result of in vivo X-ray radiotherapy shows that the mice tumors vanished near 3 weeks after radiation. Interestingly, these results show that Bi2S3@BSA-FA-CUR with the aid of X-ray can clearly promote the efficacy of chemoradiation therapy.

New Insight about Biocompatibility and Biodegradability of Iron Oxide Magnetic Nanoparticles: Stereological and In Vivo MRI Monitor.

Iron oxide magnetic nanoparticles (IONPs) have attracted enormous attention because of their extensive medicinal and industrial applicability. PEGylated L-arginine modified iron oxide magnetic nanoparticles (PEG-Arg@IONPs) were synthesized and functioned in the present research as MRI contrast agents considered in vivo BALB/c model. The Synthesized PEG-Arg@IONPs were tracked in certain time intervals by MRI. The intensity of MR imaging of kidneys increased after administration of PEG-Arg@IONPs, which could confirm the emission of these nanoparticles by kidneys shortly after administration. Although PEG-Arg@IONPs were uptake by liver within 2 hours after injection, whereas, the signal change intensity of spleen, heart and kidneys confirmed that PEG-Arg@IONPs existed in other organs. The results illustrated that IONPs coated with PEGylated natural amino acid thin layers had a long circulation time and could be served as T2 contrast agents for diagnosis purpose. Notably, to the best of our knowledge, it was the first time the biocompatibility and biodegradability of IONPs was studied and evaluated by stereological and MRI technique.

Facile Synthesis and Characterization of L-Aspartic Acid Coated Iron Oxide Magnetic Nanoparticles (IONPs) For Biomedical Applications.

Natural L-aspartic acid coated iron oxide magnetic nanoparticles (Asp@IONPs) were prepared by a one pot, in-situ and green co-precipitation method in an aqueous medium. Functionalized iron oxide magnetic nanoparticles (IONPs) were characterized by Vibrating Sample Magnetometer (VSM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) and Transmission electron microscopy (TEM) techniques. Cellular toxicity of IONPs was also investigated on HEK-293 cell lines. The results showed that the zeta potential of Asp@IONPs was about -21.1 mV and the average size was 17.80±3.09 nm. Cell toxicity results show that as prepared IONPs are biocompatible. Asp@IONPs show the possibility of using these nanoparticles in the development of in vitro and in vivo biomedical fields due to do not possess a toxic effect, good ζ-potential and related small and narrow size distribution.

Preparation of magnetic albumin nanoparticles via a simple and one-pot desolvation and co-precipitation method for medical and pharmaceutical applications.

In this study, iron oxide magnetic bovine serum albumin core-shell nanoparticles (BSA coated IONPs) with narrow particle size distribution were synthesized under one-pot reaction via the desolvation and chemical co-precipitation method. Functionalized IONPs were characterized by X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM) techniques. Furthermore, vibrating sample magnetometer (VSM) analysis show these nanoparticles (NPs) have an excellent magnetic properties. Cellular toxicity of IONPs was also investigated on HFF2 cell lines. Additionally, a hemolysis test of as prepared core-shell NPs were performed. The presence of albumin as a biomolecule coating on the surface of IONPs showed an improving effect to reduce the cytotoxicity. The properties of the designed NPs propose the BSA coated IONPs as a promising candidate for multifunctional biomedical applications.

Production of biological nanoparticles from bovine serum albumin as controlled release carrier for curcumin delivery.

This study described a curcumin (CUR) loaded bovine serum albumin nanoparticles (BSA@CUR NPs), which could solubilize the poorly water-soluble drug and increase the therapeutic efficacy of the drug. BSA@CUR NPs were synthesized by a simple coacervation procedure. The resultant BSA@CUR NPs showed a spherical shape, with a diameter of 92.59±16.75nm (mean ± SD) nm and a ζ-potential of - 9.19mV. The in vitro drug release study of CUR showed a sustained and controlled release pattern. Cellular toxicity of BSA NPs was also investigated on HFF2 cell lines. Additionally, a hemolysis test of as prepared NPs were performed for investigation of hemocompatibility. Hemolysis assay and cytotoxicity study results on HFF-2 cell line show that as prepared BSA NPs are biocompatible. The in vitro anticancer activity of the BSA@CUR NPs were performed by MTT assay on MCF-7 cancer cells. These results suggest that BSA@CUR NPs are a new drug delivery system for cancer therapy.