Hamed Nosrati

Among the potent anticancer agents, methotrexate (MTX) is very effective against many different types of cancer cells. Implementation of chemotherapy along with radiotherapy, known as synchronous chemoradiotherapy, can augment the treatment efficacy. In the present study self‐assembled MTX conjugated mPEG‐PCL copolymer encapsulating gold nanoparticles (AuNPs) hybrid (mPEG‐PCL‐MTX@Au) was developed as both drug carrier and radiosensitizer. After successful synthesis and characterization of hybrids with different techniques such as hydrogen nuclear magnetic resonance (HNMR), Fourier transform infrared spectroscopy (FTIR), ultraviolet–visible (UV‐Vis), x‐ray diffraction analysis (XRD), dynamic light scattering (DLS), and transmission electron microscopy (TEM). The anticancer activity of designed system was evaluated with a series of biological assays. TEM image indicate that AuNPs encapsulated by self‐assembled mPEG‐PCL‐MTX NPs. It was found that the micelle of that shown in the TEM image contains nine gold nanoparticles (NPs). The hydrodynamic diameter of mPEG‐PCL‐MTX@Au was 81.40 ± 8 nm. As a result, at acidic pH, which simulates tumor tissue, the most drug release is done compared to neutral pH conditions, which are the physiological conditions of the body. About 70% of the drug was released in acidic pH, while in alkaline pH, it was about 35%. The effectiveness of cancer treatment was significantly improved by using developed NPs, which introduces simultaneous chemotherapy and radiotherapy. MTT and apoptosis assays show that the mPEG‐PCL‐MTX@Au as the final formulation improves the radiosensitivity of the 4T1 breast cancer cells and also remarkably kills breast cancer. Furthermore, the result revealed that designed hybrid system extremely able to produce reactive oxygen species (ROS) within cancer cells. These results offer powerful evidence for the potential capability of mPEG‐PCL‐MTX@Au in radiosensitization of malignant tumors and opens up a new avenue of research in this area.

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.

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.

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.