Periodic Reporting for period 1 - NanoTAS (Nanoagent-based three-method treatment for atherosclerosis: Combination of thermal, mechanical, and drug-based methods)
Reporting period: 2023-02-01 to 2025-01-31
Atherosclerosis, a vascular disease, is one of the leading causes of endangering human health; so that its severe and developed stages follow up irrecoverable outcomes such as heart attacks and strokes that result in killing large numbers of patients every year worldwide. In a general definition, the Atherosclerosis refers to the accumulation and deposition of plaques (lipids, extracellular matrix, and cellular debris) in blood vessels, leading to narrowing the vessels. However, it has recently been demonstrated that the Atherosclerosis is essentially an inflammatory process in which inflammatory macrophages contribute to plaque formation and consequently play pivotal roles in the blood vessel stenosis and disease progress.
The aim of NanoTAS is to implement of an efficient treatment for the atherosclerosis disease based on thermal treatment using heat-generating nano-structured agents (NAs). The heat generation for thermal treatment is accomplished using the thermal ability of the NAs which can remotely be activated by physical stimuli such as alternating magnetic field (known as magnetic hyperthermia Therapy; MHT) and near infrared laser (known as photothermal therapy; PTT). Accordingly, the main objective of NanoTAS is design and synthesis of biocompatible NAs with high heating efficiencies under external stimuli, that are able to significantly damage to inflammatory macrophage cells. Although such a thermal treatment is mostly focused on the cancer treatment, it is expected to take one step further and play an important role in the decrease of the inflammation in the atherosclerosis disease.
The aim of NanoTAS is to implement of an efficient treatment for the atherosclerosis disease based on thermal treatment using heat-generating nano-structured agents (NAs). The heat generation for thermal treatment is accomplished using the thermal ability of the NAs which can remotely be activated by physical stimuli such as alternating magnetic field (known as magnetic hyperthermia Therapy; MHT) and near infrared laser (known as photothermal therapy; PTT). Accordingly, the main objective of NanoTAS is design and synthesis of biocompatible NAs with high heating efficiencies under external stimuli, that are able to significantly damage to inflammatory macrophage cells. Although such a thermal treatment is mostly focused on the cancer treatment, it is expected to take one step further and play an important role in the decrease of the inflammation in the atherosclerosis disease.
The main activities performed in this project can be summarized as bellow:
1- Magnetite nanorods were synthesized by various wet chemistry methods, and then, their physico-chemical properties were characterized by different analyses including HRTEM, XRD, VSM, XPS, DLS, FTIR, TG, etc. The magnetite nanorods showed significant magnetic properties and prominent potential to act as dual-responsive heat-generating NAs in the MHT and PTT.
2- The magnetite nanorods were covered with different biocompatible polymers using in-situ or ex-situ methods. Several synthesis methods were used to produce the magnetite nanorods with a perfect morphology and surface coating because the polymer coating process, in many cases, caused significant adverse changes in the morphology and the purity of magnetite phase. Finally, highly stable, water soluble, and multi-core polyethylenemine-coated magnetite nanorods (as final NAs) were synthesized through a robust multi-step method based on hydrolysis procedure. The self-assembly of the nanorods to a multi-core state causes to significantly strengthen the magnetic properties and magneto/photothermal efficiency. Moreover, the NAs were investigated in terms of biocompatibility and heat-generating ability and the results revealed a high degree of biocompatibility and magnetic hyperthermia efficiency.
3- The NAs were added to inflammatory macrophages (cell line RAW 264.7) that are responsible for atherosclerosis disease. After ensuring the uptake of the NAs by inflammatory macrophage cells through HRTEM analysis, the cells were subjected to an alternating magnetic field. The analysis of cell viability by confocal microscopy revealed that a significant percent of the treated cells with the NAs and MHT underwent cellular death. As a main result, The NAs showed high degree of anti-inflammation ability which is of high importance in the atherosclerosis treatment.
1- Magnetite nanorods were synthesized by various wet chemistry methods, and then, their physico-chemical properties were characterized by different analyses including HRTEM, XRD, VSM, XPS, DLS, FTIR, TG, etc. The magnetite nanorods showed significant magnetic properties and prominent potential to act as dual-responsive heat-generating NAs in the MHT and PTT.
2- The magnetite nanorods were covered with different biocompatible polymers using in-situ or ex-situ methods. Several synthesis methods were used to produce the magnetite nanorods with a perfect morphology and surface coating because the polymer coating process, in many cases, caused significant adverse changes in the morphology and the purity of magnetite phase. Finally, highly stable, water soluble, and multi-core polyethylenemine-coated magnetite nanorods (as final NAs) were synthesized through a robust multi-step method based on hydrolysis procedure. The self-assembly of the nanorods to a multi-core state causes to significantly strengthen the magnetic properties and magneto/photothermal efficiency. Moreover, the NAs were investigated in terms of biocompatibility and heat-generating ability and the results revealed a high degree of biocompatibility and magnetic hyperthermia efficiency.
3- The NAs were added to inflammatory macrophages (cell line RAW 264.7) that are responsible for atherosclerosis disease. After ensuring the uptake of the NAs by inflammatory macrophage cells through HRTEM analysis, the cells were subjected to an alternating magnetic field. The analysis of cell viability by confocal microscopy revealed that a significant percent of the treated cells with the NAs and MHT underwent cellular death. As a main result, The NAs showed high degree of anti-inflammation ability which is of high importance in the atherosclerosis treatment.
NanoTAS research contributes to the development of an effective thermal treatment for the atherosclerosis disease based on the heat-generating NAs. The NAs, polyethylenemine-coated magnetite nanorods, showed high degree of biocompatibility and anti-inflammation ability on the inflammatory macrophage cells (cell line RAW 264.7) that are responsible for atherosclerosis disease. Further research on the results (i.e. in vivo evaluations through animal and human trials) is expected to provide new therapeutic approaches for the researchers from treatment sector. Moreover, The NanoTAS results might not only contribute to the improvement of the life quality of atherosclerosis patients but also can be useful for other research fields such as cancer treatment, drug delivery, and contrast agent for different imaging modalities.