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    Nanocaged platforms: Modification, drug delivery and nanotoxicity. Opening synthetic cages to release the tiger

    , Article Nanoscale ; Volume 9, Issue 4 , 2017 , Pages 1356-1392 ; 20403364 (ISSN) Sahandi Zangabad, P ; Karimi, M ; Mehdizadeh, F ; Malekzad, H ; Ghasemi, A ; Bahrami, S ; Zare, H ; Moghoofei, M ; Hekmatmanesh, A ; Hamblin, M. R ; Sharif University of Technology
    Royal Society of Chemistry  2017
    Abstract
    Nanocages (NCs) have emerged as a new class of drug-carriers, with a wide range of possibilities in multi-modality medical treatments and theranostics. Nanocages can overcome such limitations as high toxicity caused by anti-cancer chemotherapy or by the nanocarrier itself, due to their unique characteristics. These properties consist of: (1) a high loading-capacity (spacious interior); (2) a porous structure (analogous to openings between the bars of the cage); (3) enabling smart release (a key to unlock the cage); and (4) a low likelihood of unfavorable immune responses (the outside of the cage is safe). In this review, we cover different classes of NC structures such as virus-like... 

    Chemo-mechanistic multi-scale model of a three-dimensional tumor microenvironment to quantify the chemotherapy response of cancer

    , Article Biotechnology and Bioengineering ; Volume 118, Issue 10 , 2021 , Pages 3871-3887 ; 00063592 (ISSN) Nikmaneshi, M. R ; Firoozabadi, B ; Mozafari, A ; Sharif University of Technology
    John Wiley and Sons Inc  2021
    Abstract
    Exploring efficient chemotherapy would benefit from a deeper understanding of the tumor microenvironment (TME) and its role in tumor progression. As in vivo experimental methods are unable to isolate or control individual factors of the TME, and in vitro models often cannot include all the contributing factors, some questions are best addressed with mathematical models of systems biology. In this study, we establish a multi-scale mathematical model of the TME to simulate three-dimensional tumor growth and angiogenesis and then implement the model for an array of chemotherapy approaches to elucidate the effect of TME conditions and drug scheduling on controlling tumor progression. The... 

    Optimization of Combination Chemotherapy Problem with Uncertain Cell Cxycle

    , M.Sc. Thesis Sharif University of Technology Jafari, Ali (Author) ; Rafiee, Majid (Supervisor) ; Najafi, Mehdi (Supervisor)
    Abstract
    Nowadays, chemotherapy is one of the common ways to treat cancer. Although, chemotherapy is used to kill cancer cells , chemotherapy drugs also target healthy cells and tissues of the body. In practice, it is difficult to strike a balance between injectable doses of drugs and toxicity in the body, and physicians are always looking for an effective treatment plan. One of the most common drugs that physicians use in chemotherapy is cell-cycle-specific drugs. These types of chemotherapy drugs affect only a certain phase of cell cycle and to a certain extent. Since the lifetime of the cancer cells is uncertain, the effective use of these drugs depends on the correct injection time of the drugs... 

    Optimal-Robust Control of Drug Delivery in Cancer Chemotherapy

    , M.Sc. Thesis Sharif University of Technology Hosseini, Fatemeh (Author) ; Moradi, Hamed (Supervisor)
    Abstract
    Chemotherapy is a proven and effective systematic approach to treat various types of cancers. Despite its advantages, chemotherapy would kill healthy as well as cancer cells. To overcome this problem, different controlling strategies are implemented. This study aims to provide a medicine drug delivery schedule for chemotherapy (by designing a proper controlling system) based on the verifiable mathematical models. First, the dynamic model is analysed and stability points are reviewed. The selected model has five state variables and two inputs. In this study, the focus is on dynamic model analysis and obtaining an effective and appropriate treatment pattern by designing a proper controller. To... 

    Using Robust Control in Drug and Virus Scheduling in Chemovirotherapy Nonlinear Model

    , M.Sc. Thesis Sharif University of Technology Mobaraki, Mobina (Author) ; Moradi, Hamed (Supervisor)
    Abstract
    Best cancer treatment is the one which reduces the tumor density in minimum time and side effects, considering the input limitations. In this paper, tracking controller and robust controllers are designed to achieve the mentioned objectives, simultaneously. An ODE-based mathematical model of the human body under chemovirotherapy is selected, which includes the uninfected and infected tumor cells, free viruses, immune cells, and a chemotherapeutic drug. For tracking purposes, a servo controller based on the entire eigenstructure assignment (EESA) approach is applied to the model, continuously and discretely. For robust purposes H-infinity and D-K iteration approaches are implemented and... 

    Asymptotic Analysis and Optimal Control of an Integro-Differential System Modeling Healthy and Cancer Cells Exposed to Chemotherapy

    , M.Sc. Thesis Sharif University of Technology Vosooq Nejad, Parisa (Author) ; Hesaraki, Mahmoud (Supervisor)
    Abstract
    We consider a system of two coupled integro-differential equations modelling populations of healthy and cancer cells under chemotherapy. Both populations are structured by a phenotypic variables, representing their level of resistance to the treatment. we analyse the asymptotic behaviour of the model under constant infusion of drugs. By designing an appropriate Lyapunov function, we prove that both cell densities converge to Dirac masses. We then define an optimal control problem, by considering all possible infusion protocols and minimising the number of cancer cells over a prescribed time frame. We provide a quasi-optimal strategy and prove that it solves this problem for large final... 

    Immunotherapy of Cancer Tumors Using Model Predictive Control Approach

    , M.Sc. Thesis Sharif University of Technology Mirbak, Mohammad (Author) ; Pishvaie, Mahmoud Reza (Supervisor)
    Abstract
    Statistics show that cancer is the second leading cause of death in the world. In recent years, several studies have shown that combination therapy is more effective than single therapy. Modeling and simulation the dynamics of cancer and the immune system and controlling the dose of cancer drugs complement preclinical trials. The aim of this study was to apply the model predictive control approach to determine the optimal dose of chemotherapy and immunotherapy drugs to treat cancerous tumors. Thus, with a preliminary analysis of the analytics, a six-state dynamic model has been selected as a hypothetical patient to advance therapeutic goals. Two sets of parameters for the hypothetical... 

    Carbosilane dendrimers: Drug and gene delivery applications

    , Article Journal of Drug Delivery Science and Technology ; Volume 59 , 2020 Rabiee, N ; Ahmadvand, S ; Ahmadi, S ; Fatahi, Y ; Dinarvand, R ; Bagherzadeh, M ; Rabiee, M ; Tahriri, M ; Tayebi, L ; Hamblin, M. R ; Sharif University of Technology
    Editions de Sante  2020
    Abstract
    Carbosilane dendrimers are a particular type of dendrimer structure that has been used as delivery vehicles for drugs and nucleic acids. They have a defined structure according to their generation number, and their terminal groups can be rendered cationic or anionic. The cationic charges can address the limitation of electrostatic repulsion between the negatively charged phosphate groups of nucleic acids and negatively charged cell membranes. Specific drugs can be loaded into the central part of the dendrimer or attached at the exterior, and the overall positive charge may improve the efficacy of anti-inflammatory drugs. One promising feature of dendrimers is their non-toxicity both in vitro... 

    A critical review of bioceramics for magnetic hyperthermia

    , Article Journal of the American Ceramic Society ; 2021 ; 00027820 (ISSN) Sedighi, O ; Alaghmandfard, A ; Montazerian, M ; Baino, F ; Sharif University of Technology
    Blackwell Publishing Inc  2021
    Abstract
    Magnetic hyperthermia (HT) using biocompatible ceramics is a ground-breaking, competent, and safe thermo-therapeutic strategy for cancer treatment. The magnetic properties of bioceramics, along with their structure and synthesis parameters, are responsible for the controlled heating of malignant tumors and are the key to clinical success. After providing a brief overview of magnetism and its significance in biomedicine, this review deals with materials selection and synthesis methods of bioceramics/glasses used for HT. Relevant research carried out on promising bioceramics for magnetic HT, with a focus on their size, shape, surface functionalization, magnetic field parameters, and in... 

    A critical review of bioceramics for magnetic hyperthermia

    , Article Journal of the American Ceramic Society ; Volume 105, Issue 3 , 2022 , Pages 1723-1747 ; 00027820 (ISSN) Sedighi, O ; Alaghmandfard, A ; Montazerian, M ; Baino, F ; Sharif University of Technology
    John Wiley and Sons Inc  2022
    Abstract
    Magnetic hyperthermia (HT) using biocompatible ceramics is a ground-breaking, competent, and safe thermo-therapeutic strategy for cancer treatment. The magnetic properties of bioceramics, along with their structure and synthesis parameters, are responsible for the controlled heating of malignant tumors and are the key to clinical success. After providing a brief overview of magnetism and its significance in biomedicine, this review deals with materials selection and synthesis methods of bioceramics/glasses used for HT. Relevant research carried out on promising bioceramics for magnetic HT, with a focus on their size, shape, surface functionalization, magnetic field parameters, and in... 

    Optimal robust control of drug delivery in cancer chemotherapy: A comparison between three control approaches

    , Article Computer Methods and Programs in Biomedicine ; Volume 112, Issue 1 , 2013 , Pages 69-83 ; 01692607 (ISSN) Moradi, H ; Vossoughi, G ; Salarieh, H ; Sharif University of Technology
    2013
    Abstract
    During the drug delivery process in chemotherapy, both of the cancer cells and normal healthy cells may be killed. In this paper, three mathematical cell-kill models including log-kill hypothesis, Norton-Simon hypothesis and Emax hypothesis are considered. Three control approaches including optimal linear regulation, nonlinear optimal control based on variation of extremals and H∞-robust control based on μ-synthesis are developed. An appropriate cost function is defined such that the amount of required drug is minimized while the tumor volume is reduced. For the first time, performance of the system is investigated and compared for three control strategies; applied on three nonlinear models... 

    Nonlinear composite adaptive control of cancer chemotherapy with online identification of uncertain parameters

    , Article Biomedical Signal Processing and Control ; Volume 49 , 2019 , Pages 360-374 ; 17468094 (ISSN) Sharifi, M ; Moradi, H ; Sharif University of Technology
    Elsevier Ltd  2019
    Abstract
    A new composite adaptive control strategy is developed for both of the reduction of cancer tumor volume and the online identification of tumor parameters during the drug delivery process in chemotherapy. This control strategy is developed for three different nonlinear mathematical cell-kill models of the cancer tumor including the log-kill hypothesis, Norton-Simon hypothesis and Emax hypothesis. All of these models are considered to have fully parametric uncertainties. The stability, tracking convergence and parameters identification convergence during the chemotherapy process are proved using the Lyapunov method. For the first time, the parameters identification of the uncertain... 

    Investigation of cancer response to chemotherapy: a hybrid multi-scale mathematical and computational model of the tumor microenvironment

    , Article Biomechanics and Modeling in Mechanobiology ; Volume 21, Issue 4 , 2022 , Pages 1233-1249 ; 16177959 (ISSN) Nikmaneshi, M. R ; Firoozabadi, B ; Sharif University of Technology
    Springer Science and Business Media Deutschland GmbH  2022
    Abstract
    Tumor microenvironment (TME) is a multi-scale biological environment that can control tumor dynamics with many biomechanical and biochemical factors. Investigating the physiology of TME with a heterogeneous structure and abnormal functions not only can achieve a deeper understanding of tumor behavior but also can help develop more efficient anti-cancer strategies. In this work, we develop a hybrid multi-scale mathematical model of TME to simulate the progression of a three-dimensional tumor and elucidate its response to different chemotherapy approaches. The chemotherapy approaches include multiple low dose (MLD) of anti-cancer drug, maximum tolerated dose (MTD) of anti-cancer drug,... 

    Development of a Meta-heuristic Algorithm based on Chemotherapy Science

    , Ph.D. Dissertation Sharif University of Technology Salmani, Mohammad Hassan (Author) ; Eshghi, Kourosh (Supervisor)
    Abstract
    Among scientific fields of study, mathematical programming has high status and its importance has led researchers to develop accurate models and effective solving approaches to addressing optimization problems. In particular, meta-heuristic algorithms are approximate methods for solving optimization problems whereby good (not necessarily optimum) solutions can be generated via their implementation. In this study, we propose a population-based meta-heuristic algorithm according to chemotherapy method to cure cancers that mainly search the infeasible region. As in chemotherapy, Chemotherapy Science Algorithm (CSA) tries to kill inappropriate solutions (cancers and bad cells of the human body);... 

    An Experimental Study of Cancer Treatment Using Combined Hyperthermia and Chemotherapy Methods

    , Ph.D. Dissertation Sharif University of Technology Khafaji, Mona (Author) ; Vosoghi, Manoucher (Supervisor) ; Hormozinezhad, Mohammad Reza (Supervisor) ; Dinarvand, Rasoul (Supervisor) ; Iraji Zad, Azam (Co-Advisor)
    Abstract
    Cancer treatment is one of the most challenging issues of recent years. Extensive researches have been conducted in various fields of medicine, pharmacy, and medical physics in this regard. Today, considering nanotechnology developments, researchers believe that full cancer treatment is possible through the use of nano-systems designed with scientific background to overcome the defects of previous methods. In this research, the main purpose is to design and synthesize multifunctional hybrid nanostructures with favorable optical and magnetic properties providing a way to combine chemotherapy and thermal treatment. Accordingly, two different structures were designed and experimentally... 

    Robust Optimal Control of Drug Delivery in Cancer Chemotherapy based on a New Realistic Dynamic Model of the Process

    , M.Sc. Thesis Sharif University of Technology Rafiei, Behrooz (Author) ; Moradi, Hamed (Supervisor)
    Abstract
    Today, cancer mortality is one of the most important problems, even considering the scientific advances that offer more effective solutions to treat some diseases, providing a way to prevent and treat this disease is one of the most important issues that engineers have considered. This is achieved by designing a controller to minimize the size of the cancer tumor population, increase healthy cells, optimize treatment time, and drug dose.To achieve this goal, pharmacokinetic, pharmacodynamic, tumor growth, and healthy cell growth models, and mathematical models for subsystems that affect tumor growth, such as the angiogenic system, have been studied to develop a single mathematical model. In... 

    Synthesis and Evaluation of Molybdenum Disulfide for Combined Photothermal-chemo Therapy

    , Ph.D. Dissertation Sharif University of Technology Salimi, Marzieh (Author) ; Vosoughi, Manouchehr (Supervisor) ; Shokrgozar, Mohammad Ali (Supervisor) ; Delavari, Hamid (Co-Supervisor)
    Abstract
    New methods of cancer treatment are always the attention of researchers all over the world, among which the photothermal treatment method is of particular importance. In addition to being easy, this treatment method has the least invasiveness. Studies have shown that combining this method with other methods such as chemotherapy not only can be very effective in destroying tumor tissue, but can significantly reduce the side effects of chemotherapy drugs.In order to apply the photothermal treatment method, an effective photothermal agent is needed. Molybdenum disulfide nanosheets have performed successfully in this field, which have been of great interest, due to their high efficiency in... 

    Navigating drug-like chemical space of anticancer molecules using genetic algorithms and counterpropagation artificial neural networks

    , Article Molecular Informatics ; Volume 31, Issue 1 , JAN , 2012 , Pages 63-74 ; 18681743 (ISSN) Jalali Heravi, M ; Mani Varnosfaderani, A ; Sharif University of Technology
    2012
    Abstract
    A total of 6289 drug-like anticancer molecules were collected from Binding database and were analyzed by using the classification techniques. The collected molecules were encoded to a diverse set of descriptors, spanning different physical and chemical properties of the molecules. A combination of genetic algorithms and counterpropagation artificial neural networks was used for navigating the generated drug-like chemical space and selecting the most relevant molecular descriptors. The proposed method was used for the classification of the molecules according to their therapeutic targets and activities. The selected molecular descriptors in this work define discrete areas in chemical space,... 

    Observer based feedback control of a biodynamical model of tumor growth with sampled measurements

    , Article 2016 European Control Conference, ECC 2016, 29 June 2016 through 1 July 2016 ; 2017 , Pages 2423-2428 ; 9781509025916 (ISBN) Gholami, S ; Salarieh, H ; Alasty, A ; Sharif University of Technology
    Institute of Electrical and Electronics Engineers Inc  2017
    Abstract
    This paper deals with the cancer treatment scheduling via observer-based feedback control of a tumor growth biodynamical model. An experimental nonlinear model is utilized to design a feedback controller. This model was validated by a pharmacological study on xenograft models obtained by transplantation of colon carcinoma cell lines in athymic mice. Input-output feedback linearization approach is used to linearize the nonlinear model of the system and design a control law. It is assumed that tumor weight can be measured in definite intervals. So a continuous-discrete observer is designed to estimate states of the system based on discrete sampled data which are tumor weight in this case. To... 

    Design of robust control strategy in drug and virus scheduling in nonlinear process of chemovirotherapy

    , Article Computers and Chemical Engineering ; Volume 150 , 2021 ; 00981354 (ISSN) Mobaraki, M ; Moradi, H ; Sharif University of Technology
    Elsevier Ltd  2021
    Abstract
    Since the injection of the oncolytic viruses in the virotherapy process reduces the toxicity and drug resistance inherent in the chemotherapy; chemovirotherapy as a novel combination therapy has become an efficient cancer treatment. The primary purpose of this paper is to design a robust optimal control strategy for the chemovirotherapy through which the tumor density decreases to its stable condition with limited drug and virus delivery. This desired treatment should be responsive in the presence of input disturbances and parametric uncertainties. In this regard, an ODE (Ordinary Differential Equation) mathematical model of the chemovirotherapy process presenting the connection between the...