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    Optimal-Robust Control of Drug Delivery in Cancer Chemotherapy

    , M.Sc. Thesis Sharif University of Technology Hosseini, Fatemeh (Author) ; Moradi, Hamed (Supervisor)
    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)
    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)
    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)
    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... 

    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
    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... 

    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
    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... 

    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)
    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)
    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
    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,... 

    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
    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
    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... 

    Graphene oxide functionalized with oxygen-rich polymers as a pH-sensitive carrier for co-delivery of hydrophobic and hydrophilic drugs

    , Article Journal of Drug Delivery Science and Technology ; Volume 56 , 2020 Pourjavadi, A ; Asgari, S ; Hosseini, S. H ; Sharif University of Technology
    Editions de Sante  2020
    In this work, a novel carrier based-on modified graphene oxide was designed for co-delivery of hydrophobic and hydrophilic anticancer drugs (curcumin (Cur) and doxorubicin (DOX) as the model of drugs). The hydroxyl groups at the edges of graphene oxide (GO) sheets were used as the initiation sites for growing poly(epichlorohydrin) (PCH) chains. Then, hyperbranched polyglycerol (HPG) was grafted on the hydroxyl end groups of PCH (PCH-g-HPG). Pendant chlorines in the main chain of GO-PCH-g-HPG were replaced with hydrazine. The modification of GO sheets with oxygen-rich polymers increased water solubility of graphene oxide. Doxorubicin was loaded onto the nanocarrier by covalent bonding with... 

    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
    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... 

    Tunable surface plasmon resonance–based remote actuation of bimetallic core-shell nanoparticle-coated Stimuli responsive polymer for switchable chemo-photothermal synergistic cancer therapy

    , Article Journal of Pharmaceutical Sciences ; Volume 107, Issue 10 , 2018 , Pages 2618-2627 ; 00223549 (ISSN) Amoli Diva, M ; Sadighi Bonabi, R ; Pourghazi, K ; Hadilou, N ; Sharif University of Technology
    New dual light/temperature-responsive nanocarriers were synthesized using bimetallic plasmonic Au-Ag and Ag-Au nanoparticles (NPs) as cores of vehicles which subsequently functionalized with an upper critical solubility temperature–based poly acrylamide-co-acrylonitrile using reversible addition-fragmentation chain transfer for spatiotemporally controlled chemo-photothermal synergistic cancer therapy. The bimetallic cores were assigned to sense wavelengths close to the localized surface plasmon resonance of monometallic NP shell to produce heat which not only can increase the surrounding temperature over the upper critical solubility temperature of polymer to open its valves and promote drug... 

    Doxorubicin hydrochloride - loaded electrospun chitosan/cobalt ferrite/titanium oxide nanofibers for hyperthermic tumor cell treatment and controlled drug release

    , Article International Journal of Biological Macromolecules ; Volume 116 , 2018 , Pages 378-384 ; 01418130 (ISSN) Radmansouri, M ; Bahmani, E ; Sarikhani, E ; Rahmani, K ; Sharifianjazi, F ; Irani, M ; Sharif University of Technology
    In the present study, the potential of doxorubicin hydrochloride (DOX)-loaded electrospun chitosan/cobalt ferrite/titanium oxide nanofibers was studied to investigate the simultaneous effect of hyperthermia and chemotherapy against melanoma cancer B16F10 cell lines. The cobalt ferrite nanoparticles were synthesized via microwave heating method. The titanium oxide nanoparticles were mixed with cobalt ferrite to control the temperature rise. The synthesized nanoparticles and nanofibers were characterized using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and vibrating sample magnetometer (VSM) analysis. The DOX loading efficiency and in vitro drug release of... 

    Inorganic nanomaterials for chemo/photothermal therapy: a promising horizon on effective cancer treatment

    , Article Biophysical Reviews ; Volume 11, Issue 3 , 2019 , Pages 335-352 ; 18672450 (ISSN) Khafaji, M ; Zamani, M ; Golizadeh, M ; Bavi, O ; Sharif University of Technology
    Springer Verlag  2019
    During the last few decades, nanotechnology has established many essential applications in the biomedical field and in particular for cancer therapy. Not only can nanodelivery systems address the shortcomings of conventional chemotherapy such as limited stability, non-specific biodistribution and targeting, poor water solubility, low therapeutic indices, and severe toxic side effects, but some of them can also provide simultaneous combination of therapies and diagnostics. Among the various therapies, the combination of chemo- and photothermal therapy (CT-PTT) has demonstrated synergistic therapeutic efficacies with minimal side effects in several preclinical studies. In this regard,...