Abstract:For the first time, inspired by magnetic resonance imaging-guidance high intensity focused ultrasound (MR-HIFU) technology, i.e., medication therapy and thermal ablation in one session, in a preclinical setting based on a developed mathematical model, the performance of doxorubicin (Dox) and its encapsulation have been investigated in this study. Five different treatment methods, that combine medication therapy with mild hyperthermia by MRI contrast ($$\gamma -{Fe}_{2}{O}_{3}$$
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“…The obtained value for IFP is consistent with the experimental investigations of Huber et al 69 and Arifin et al 70 , and the numerical studies of Sefidgar et al 27 , Soltani et al 71 , and Moradi Kashkooli et al 32 , 72 . The IFV amount (median value ~ 0.031 µm/s) is also in good correspondence with numerical studies of Pishko et al 73 , Souri et al 74 , and Zhao et al 75 ; and in the same order with the value reported by experimental study of Homopland et al 76 .…”
The development of an in silico approach that evaluates and identifies appropriate treatment protocols for individuals could help grow personalized treatment and increase cancer patient lifespans. With this motivation, the present study introduces a novel approach for sequential treatment cycles based on simultaneously examining drug delivery, tumor growth, and chemotherapy efficacy. This model incorporates the physical conditions of tumor geometry, including tumor, capillary network, and normal tissue assuming real circumstances, as well as the intravascular and interstitial fluid flow, drug concentration, chemotherapy efficacy, and tumor recurrence. Three treatment approaches—maximum tolerated dose (MTD), metronomic chemotherapy (MC), and chemo-switching (CS)—as well as different chemotherapy schedules are investigated on a real tumor geometry extracted from image. Additionally, a sensitivity analysis of effective parameters of drug is carried out to evaluate the potential of using different other drugs in cancer treatment. The main findings are: (i) CS, MC, and MTD have the best performance in reducing tumor cells, respectively; (ii) multiple doses raise the efficacy of drugs that have slower clearance, higher diffusivity, and lower to medium binding affinities; (iii) the suggested approach to eradicating tumors is to reduce their cells to a predetermined rate through chemotherapy and then apply adjunct therapy.
“…The obtained value for IFP is consistent with the experimental investigations of Huber et al 69 and Arifin et al 70 , and the numerical studies of Sefidgar et al 27 , Soltani et al 71 , and Moradi Kashkooli et al 32 , 72 . The IFV amount (median value ~ 0.031 µm/s) is also in good correspondence with numerical studies of Pishko et al 73 , Souri et al 74 , and Zhao et al 75 ; and in the same order with the value reported by experimental study of Homopland et al 76 .…”
The development of an in silico approach that evaluates and identifies appropriate treatment protocols for individuals could help grow personalized treatment and increase cancer patient lifespans. With this motivation, the present study introduces a novel approach for sequential treatment cycles based on simultaneously examining drug delivery, tumor growth, and chemotherapy efficacy. This model incorporates the physical conditions of tumor geometry, including tumor, capillary network, and normal tissue assuming real circumstances, as well as the intravascular and interstitial fluid flow, drug concentration, chemotherapy efficacy, and tumor recurrence. Three treatment approaches—maximum tolerated dose (MTD), metronomic chemotherapy (MC), and chemo-switching (CS)—as well as different chemotherapy schedules are investigated on a real tumor geometry extracted from image. Additionally, a sensitivity analysis of effective parameters of drug is carried out to evaluate the potential of using different other drugs in cancer treatment. The main findings are: (i) CS, MC, and MTD have the best performance in reducing tumor cells, respectively; (ii) multiple doses raise the efficacy of drugs that have slower clearance, higher diffusivity, and lower to medium binding affinities; (iii) the suggested approach to eradicating tumors is to reduce their cells to a predetermined rate through chemotherapy and then apply adjunct therapy.
“…The mean spatial value of tumor IFP for the networks 1–6 is 1525.7 Pa, 1585.5 Pa, 1698.3 Pa, 1570.2 Pa, 1700.7 Pa and 1868.2 Pa, respectively. The results are good compatible with the numerical studies of Soltani et al 61 , Souri et al 62 , Al-Zu’bi and Mohan 63 as well as the experimental study of Butcher et al 64 , which demonstrated the range of 586–4200 Pa for IFP in the tumor. Moreover, the IFP value in normal tissue is around 53.7–97.5 Pa, that agrees with the values of the experimental study 65 , 66 , which demonstrated the range of − 400 to 800 Pa for IFP in normal tissue.…”
Section: Resultssupporting
confidence: 89%
“…Indeed, the maximum value of IFV occurs at the boundary between tumor and normal tissue where there is a large IFP gradient. IFV results are in the same order as the prediction of Jain et al 38 , Soltani et al 61 , Souri et al 62 , Kashkooli et al 67 , and experimental observation of Hompland et al 68 . Figure 8 Interstitial fluid velocity distribution for six considered networks.…”
We present comprehensive mathematical modeling of radiopharmaceutical spatiotemporal distributions within vascularized solid tumors. The novelty of the presented model is at mathematical level. From the mathematical viewpoint, we provide a general modeling framework for the process of radiopharmaceutical distribution in the tumor microenvironment to enable an analysis of the effect of various tumor-related parameters on the distribution of different radiopharmaceuticals. We argue that partial differential equations (PDEs), beyond conventional methods, including ODE-based kinetic compartment modeling, can be used to evaluate radiopharmaceutical distribution in both time and space. In addition, we consider the spatially-variable dynamic structure of tumor microvascular networks to simulate blood flow distribution. To examine the robustness of the model, the effects of microvessel density (MVD) and tumor size, as two important factors in tumor prognosis, on the radiopharmaceutical distribution within the tumor are investigated over time (in the present work, we focus on the radiopharmaceutical [18F]FDG, yet the framework is broadly applicable to radiopharmaceuticals). Results demonstrate that the maximum total uptake of [18F]FDG at all time frames occurs in the tumor area due to the high capillary permeability and lack of a functional lymphatic system. As the MVD of networks increases, the mean total uptake in the tumor is also enhanced, where the rate of diffusion from vessel to tissue has the highest contribution and the rate of convection transport has the lowest contribution. The results of this study can be used to better investigate various phenomena and bridge a gap among cancer biology, mathematical oncology, medical physics, and radiology.
“…In free injection of drugs, they can damage non-infected cells, while higher doses can cause some organs to become ineffective. The unique properties of nanocarriers such as good solubility, biocompatibility, long circulation time, as well as surface performance, make them an excellent candidate for the delivery of therapeutic agents [ 28 , 244 , 245 ]. Different types of nanocarriers have been introduced for drug delivery applications ( Figure 12 ).…”
Following the announcement of the outbreak of COVID-19 by the World Health Organization, unprecedented efforts were made by researchers around the world to combat the disease. So far, various methods have been developed to combat this “virus” nano enemy, in close collaboration with the clinical and scientific communities. Nanotechnology based on modifiable engineering materials and useful physicochemical properties has demonstrated several methods in the fight against SARS-CoV-2. Here, based on what has been clarified so far from the life cycle of SARS-CoV-2, through an interdisciplinary perspective based on computational science, engineering, pharmacology, medicine, biology, and virology, the role of nano-tools in the trio of prevention, diagnosis, and treatment is highlighted. The special properties of different nanomaterials have led to their widespread use in the development of personal protective equipment, anti-viral nano-coats, and disinfectants in the fight against SARS-CoV-2 out-body. The development of nano-based vaccines acts as a strong shield in-body. In addition, fast detection with high efficiency of SARS-CoV-2 by nanomaterial-based point-of-care devices is another nanotechnology capability. Finally, nanotechnology can play an effective role as an agents carrier, such as agents for blocking angiotensin-converting enzyme 2 (ACE2) receptors, gene editing agents, and therapeutic agents. As a general conclusion, it can be said that nanoparticles can be widely used in disinfection applications outside in vivo. However, in in vivo applications, although it has provided promising results, it still needs to be evaluated for possible unintended immunotoxicity. Reviews like these can be important documents for future unwanted pandemics.
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