نانوذرات طلای حامی پیش داروی پلیمری کنژوگه شده با متوترکسات برای شیمی/رادیو درمانی ترکیبی

عنوان انگليسی

Methotrexate conjugated polymeric prodrug encapsulating gold nanoparticles for combined chemo/radiation therapies

خلاصه انگلیسی

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.

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