Les nanoparticules (NPs) d’oxyde de fer susceptibles de présenter un comportement superparamagnétique ont connu ces dernières années un intérêt considérable en vue de leur application en nanomédecine. Leurs propriétés magnétiques et biocompatibilités permettent notamment leur utilisation à des fins de diagnostic (IRM, imagerie optique et nucléaire…) et aussi de thérapie (hyperthermie, nano vectorisation…). L’objectif de cette thèse a été d’étudier l’influence des paramètres de synthèse sur les propriétés finales des NPs d’oxyde de fer magnétique dopé au zinc. Cette étude avait plus particulièrement pour but l’optimisation des méthodes de synthèse qui sont la coprécipitation et la décomposition thermique. A ce sujet, la caractérisation des NPs par diverses techniques a permis notamment d’étudier les liens entre la taille, la forme, la composition chimique d’une part, et les propriétés magnétiques des NPs d’autre part. Dans un deuxième temps, la fonctionnalisation des NPs qui est une étape indispensable pour assurer leurs biocompatibilités a été réalisée, elle était suivie par des mesures d’hyperthermie magnétique. / The superparamagnetic iron oxide nanoparticles (NPs) are a class of nanomaterials with a high interest in the nanomedicine field. Their magnetic properties and biocompatibility recommend them as potential candidates for diagnostics purposes (MRI, optical or nuclear Imaging ...) and therapy (hyperthermia, nanovectorization...). The aim of this thesis was to study the influence of the synthesis parameters on the final properties of magnetic zinc doped iron oxide nanoparticles. Two synthesis methods were considered, the co-precipitation and the thermal decomposition. The characterization of the obtained nanoparticles by complementary techniques allowed us to propose a consistent relationship between the size, shape and chemical composition on the one hand, and the magnetic properties of the nanoparticles on the other hand. The functionalization of NPs, that is a crucial step for ensuring their biocompatibility and use in magnetic hyperthermia, was also realised and the hyperthermia properties were measured on some typical nanoparticles.

Hyperthermia damages both developing and adult brains, especially when it occurs after ischemia or stroke. Work presented in this dissertation used in vitro models of these stresses to investigate mechanisms underlying damage to immature neurons and neural precursors cultured from embryonic rat brain. Studies described in Chapter 2 investigated the effects of a brief, intense hyperthermic stress (30-45 min at 43ºC). This stress produced a selective depletion of nestin-immunoreactive neural precursor cells, and reduced proliferation, as evidenced by reduced BrdU incorporation into young Tuj1-immunoreactive neurons. The stress activated caspase 3, and produced multiple signs of nuclear damage as well as early and persisting mitochondrial depolarization. Cycloheximide, an inhibitor of protein synthesis, reduced cell death. All these findings suggest an apoptotic death process. Studies described in Chapter 3 used a combination of oxygen-glucose deprivation (OGD, 2 h) followed by mild 41ºC hyperthermia for 90 min (T). The combined OGDT stress reduced both survival in monolayer cultures and colony-forming ability in neurospheres. Cell death occurred gradually over 2 days, and was accompanied by caspase activation that began within 6 h post-stress. Post-stress application of cycloheximide or a general caspase inhibitor (especially qVD-OPH) reduced cell death, but specific inhibitors of caspases 2, 3, 8 or 9 were ineffective. OGDT led to upregulation of the pro-apoptotic protein Bim as well as redistribution of Bax from cytoplasm to mitochondria within 6 h. Persisting mitochondrial depolarization began within 3 h following the combined OGDT stress, but not following individual OGD or T stresses alone. These findings suggest that OGD sensitizes neural precursor cells to hyperthermia-induced damage, and that the combined OGDT stress kills neural precursors via apoptotic mechanisms that include activation of mitochondrial death pathways. Results of these studies suggest that immature neurons and neural precursors are especially vulnerable to hyperthermia-induced damage via apoptotic mechanisms. Pan-caspase inhibitors may be a promising therapeutic strategy to preserve viability of these cells following stroke with hyperthermia.

<p>Numerous studies have shown that the combination of radiation therapy and hyperthermia, when delivered at moderate temperatures (40°-45°C) for sustained times (30-90 minutes), can help to provide palliative relief and augment tumor response, local control, and survival. However, the dependence of treatment success on achieved temperature highlights the need for accurate thermal dosimetry, so that the prescribed thermal dose can be delivered to the tumor. This can be achieved noninvasively with MR thermometry. However, there are many challenges to performing MR thermometry in the breast, where hyperthermia of locally advanced breast cancer can provide a benefit. These include magnetic field system drift, fatty tissue, and breathing motion.</p> <p>The purpose of this research was to develop a system for the hyperthermia treatment of LABC while performing MR thermometry. A hardware system was developed for performing the hyperthermia treatment within the MR bore. Methods were developed to correct for magnetic field system drift and to correct for breath hold artifacts in MR thermometry of the tumor using measurement of field changes in fat references. Lastly, techniques were developed for measuring temperature in the fatty tissue using multi-echo fat water separation methods, reducing the error of performing MR thermometry in such tissues. All of these methods were characterized with phantom and in vivo experiments in a 1.5T MR system. </p> <p>The results of this research can provide the means for successful hyperthermia treatment of LABC with MR thermometry. With this thermometry, accurate thermal doses can be obtained, potentially providing improved outcomes. However, these results are not only applicable in the breast, but can also be used for improved MR thermometry in other areas of the body, such as the extremities or abdomen.</p> / Dissertation

The clinical efficacy of chemotherapy in solid tumours is limited by systemic toxicity and the inability to deliver a cytotoxic concentration of anticancer drugs to all tumour cells. Temperature sensitive drug carriers provide a mechanism for triggering the rapid release of chemotherapeutic agents in a targeted region. Thermally mediated drug release also leverages the ability of hyperthermia to increase tumour blood flow, vessel permeability, and drug cytotoxicity. Drug release from thermosensitive liposome drug carriers in the tumour vasculature serves as a continuous intravascular infusion of free drug originating at the tumour site. However, localized drug release requires precise heating to improve drug delivery and efficacy in tumours while minimizing drug exposure in normal tissue. Focused ultrasound can noninvasively heat millimeter-sized regions deep within the body, and can be combined with MR thermometry for precise temperature control. This thesis describes the development of strategies to achieve localized hyperthermia using MRI-controlled focused ultrasound, for the purpose of image-guided heat-triggered drug release from thermosensitive drug carriers. First, a preclinical MRI-controlled focused ultrasound system was developed as a platform for studies of controlled hyperthermia and drug delivery in rabbits. The feasibility of using ultrasound hyperthermia to achieve localized doxorubicin release from thermosensitive liposomes was demonstrated in normal rabbit muscle. Second, strategies were described for using MR thermometry to control ultrasound heating at a muscle-bone interface based on MR temperature measurements in adjacent soft tissue, demonstrating localized drug delivery in adjacent muscle and bone marrow. Third, fluorescence microscopy was employed to demonstrate that increased overall drug accumulation in rabbit VX2 tumours corresponds to high levels of bioavailable drug reaching their active site in the nuclei of tumour cells. The results of this thesis demonstrate that image-guided drug delivery using thermosensitive liposomes and MRI-controlled focused ultrasound hyperthermia can be used to noninvasively achieve precisely localized drug deposition in soft tissue, at bone interfaces, and in solid tumours. Clinical application of this work could provide a noninvasive means of enhancing chemotherapy in a variety of solid tumours.

Išstudijavus mokslinius literatūros šaltinius, pastebėta, kad kūno temperatūros, o tuo pačiu ir raumens vidinės temperatūros padidėjimas sukelia daug fiziologinių reakcijų žmogaus organizme, tačiau vis dar mažai darbų, nagrinėjančių aklimacijos (aklimacija �� tai dirbtinėse sąlygose (laboratorijoje) sukelta ilgalaikė aklimatizacija) hipertermijai, sukeltos dirbtiniu būdu, poveikį žmogaus fiziologinių rodiklių kaitai, raumens išvystomai maksimaliai valingai jėgai. Nepavyko rasti duomenų kaip maksimalios valingos jėgos metu keičiasi raumenų elektrinis aktyvumas, priklausantis nuo aklimacijos hipertermijai. Pagrindinis šio darbo tikslas buvo nustatyti ir įvertinti dirbtinės aklimacijos hipertermijai poveikį �����mogaus organizmui. Uždaviniai: Nustatyti ir įvertinti žmogaus fiziologinių rodiklių (rektalinę, odos bei kūno temperatūras, fiziologinį stresą, netenkamą kūno svorį, širdies susitraukimų dažnį ir šiluminį stresą) kaitą aklimacijos hipertermijai laikotarpyje: prieš pasyvų šildymą, šildymo metu ir po šildymo; nustatyti aklimacijos hipertermijai poveikį raumenų atsparumui nuovargiui; nustatyti aklimacijos hipertermijai poveikį raumenų centriniam aktyvacijos koeficientui; nustatyti ir įvertinti aklimacijos hipertermijai poveikį šlaunies raumens elektriniam aktyvumui. Šio tyrimo metu iš viso buvo atliekami aštuoni tyrimai — vienas kontrolinis ir septyni hipertermiją sukeliantys eksperimentiniai. Eksperimentiniai nuo kontrolinio skyrėsi pasyviu kojų pašildymu (tiriamieji... [toliau žr. visą tekstą] / Firstly, it is important to emphasize that the research of different scientific articles and other sources of information has proved that the increment of temperature in the man’s body as well as the inner muscle causes many physiologic reflexes in human’s organism. However not many research projects analyzing the impact of the acclimation (In vitro(in laboratory) related long term acclimatization) to hyperthermic environment, created in imitative way, neither on the fluctuation of man’s vital functions nor on the maximum voluntary muscle strength, could be found. Secondly, it should be noted, that none of the above mentioned sources provided the information on the change of muscle electric activity at the moment of its maximum voluntary strength. Therefore, the main purpose of this research was to establish and measure the influence of the imitative acclimation of hyperthermia on the man’s body. The main tasks of the project were to observe and evaluate the change of man’s physiological functions (rectal, skin and body temperature, physiologic stress, weight loss, heart rate and thermic stress) during the acclimation to hyperthermia process: before passive heating, during the heating time and after it; to establish the impact of acclimation to hyperthermia on the maximum voluntary force as well as on the maximum activation rate; to establish and measure the impact of the acclimation to hyperthermia on the muscle electrical activity. In order to achieve the desired... [to full text]

Pagal pasaulinę sveikatos organizaciją, sveikata — tai fizinė, dvasinė ir socialinė gerovė, o ne tik ligos ar negalios nebuvimas. Svarbus sveikatą veikiantis veiksnys yra aplinkos temperatūra. Kiekvieno žmogaus organizmas puikiai geba prisitaikyti prie kintančių aplinkos temperatūros sąlygų, tačiau skirtingi žmonės įvairiai reaguoja į temperatūros pasikeitimus. Padidėjus žmogaus kūno temperatūrai gali įvykti perkaitimas — hipertermija. Probleminis klausimas. Ar dirbtinėmis sąlygomis sukėlus hipertermiją, moterų organizmas adaptuosis prie jos? Ar hipertermija riboja raumens funkcines galimybes atliekant maksimalaus intensyvumo izometrinius pratimus? Tyrimo tikslas buvo įvertinti aklimatizacijos hipertermijai ��taką moterų organizmui. Tyrimo tikslui pasiekti iškelti uždaviniai: 1. Nustatyti hipertermijos poveikį tiriamųjų širdies susitraukimų dažniui bei pulsiniam spaudimui. 2. Nustatyti tiriamųjų rektalinės, odos, bendrą kūno temperatūrų kaitą ir netenkamą kūno svorį sukėlus hipertermiją. 3. Įvertinti tiriamųjų subjektyvų šiluminį pojūtį, šiluminį komfortą bei šiluminį stresą sukėlus hipertermiją. 4. Nustatyti hipertermijos poveikį maksimaliai valingai jėgai ir centriniam nuovargiui, atliekant 2 min. maksimalų izometrinį krūvį. Išanalizavus tyrimo rezultatus nustatyta, kad septynis kartus kas antrą dieną pasyviai šildant kūną, įmerkiant kojas į vandenį, kur vandens temperatūra 44oC, bei taikant maksimalios valingos jėgos 2 minučių krūvį (MVJ-2 min.), organizmo aklimatizacija... [toliau žr. visą tekstą] / According to the world health organization, health is physical, spiritual and social well-being and not just the absence of illness or disability. An important factor that affects health is the environmental temperature. Every person’s body can adapt well to changing environment conditions, however different people react in a variety of ways to changes in temperature. Increase in human body temperature can lead to overheating - hyperthermia. The goal of the research was to evaluate the effect of acclimatization to hyperthermia to the fatigue of skeletal muscles of adult women when performing maximum intensity isometric exercises. Tasks in order to reach the goal of the research: 1. To determine the effect of hyperthermia to the subjects' heart contraction rate and pulse pressure. 2. To determine the variation of the subjects' rectal, skin and general body temperature and body weight loss during induced hyperthermia. 3. To evaluate the subjective heat sensation, heat comfort and heat stress of the subjects during induced hyperthermia. 4. To determine the effect of hyperthermia to maximum volitional strength and central fatigue when performing maximum 2 min. isometric load. After analysing the results of the research it was found that by passively heating the body every two days seven times in total, by immersing feet into water, whose temperature is 44 oC, and by applying maximum volitional strength 2 minute load (MVJ-2 min.), the acclimatisation of the body to... [to full text]

Žmogaus adaptacija prie karščio yra visapusiškai nagrinėjama ir plati problema (Hori, 1978). Literatūroje gausu tyrimų, nagrinėjančių hipertermijos poveikį neuroraumeninei funkcijai po fizinių pratimų karštyje (Nybo & Nielsen, 2001) ar pasyvaus šildymo (Thomas et al., 2006; Todd et al., 2005). M. M. Thomas et al. (2006) nustatė, kad pasyvaus šildymo metu, padidinus vidinę kūno temperatūrą iki 39,5 oC, sumažėja maksimali izometrinė pėdos lenkiamųjų raumenų jėga ir tai įtakoja raumenų aktyvacijos iš CNS sumažėjimas. Anksčiau atlikti tyrimai patvirtina, kad aukšta organizmo vidinė temperatūra paveikia CNS ir jos galimybę aktyvuoti dirbančius raumenis (Nybo & Nielsen, 2001; Todd et al., 2005). Organizmui aklimuojantis prie karščio, sumažėja TREKT, ŠSD, FSI ir padidėja prakaitavimas, kas lemia mažesnį fiziologinį-terminį stresą hipertermijos sąlygomis (Brazaitis ir kt., 2009; Brazaitis ir Skurvydas, 2010), tačiau sunku rasti tyrimų, nagrinėjančių kaip tai paveikia neuroraumeninę funkciją. M. Brazaitis ir A. Skurvydas (2010) nustatė, kad po 7 pasyvaus šildymo procedūrų (~44 oC vandenyje po 45 minutes), kurios buvo vykdomos kas antrą dieną 2 savaičių laikotarpyje, organizmas aklimavosi prie karščio, bet tai nepaveikė centrinio ir periferinio nuovargio MVJ-2min izometrinio krūvio metu hipertermijos sąlygomis. Mūsų atliktame tyrime buvo naudota unikali pasyvaus šildymo metodika (siekiama TREKT padidinti iki 39,5 0C, maksimalus šildymo procedūros laikas 120 min., šildymo procedūros... [toliau žr. visą tekstą] / Human adaptation to heat is comprehensive of a broad problem (Hori, 1978). The literature is rich in research of analyzing the influence of hyperthermia on neuromuscular function, after exercising in the heat (Nybo & Nielsen, 2001) or passive heating (Thomas et al., 2006; Todd et al., 2005). M. M. Thomas et al. (2006) ascertained that the increase to 39,5 oC of core temperature in passive heating, reduces maximal isometric force of plantar flexors and this is influence of the reduction on voluntary muscle activation from CNS. Earlier studies show, that high core temperature affects CNS and its ability to activate working muscles (Nybo & Nielsen, 2001; Todd et al., 2005). Heat acclimation occurs with reduced rectal temperature, heart rate, physiological strain index and increased sweat rate, which causes reduction in physiological-thermal stress in the hyperthermia (Brazaitis ir kt., 2009; Brazaitis ir Skurvydas, 2010), but it is difficult to find studies how this affects the neuromuscular function. M. Brazaitis & A. Skurvydas (2010) found out that after 7 passive heating procedures (in ~44 oC water, 45 minutes each), which was carried out every second day for two weeks, heat acclimation occurred, but did not change the central and peripheral fatigue during a 2-min MVC in hyperthermia. In our study, we used the unique passive heating technique (we tried to elevate rectal temperature to 39,5 0C, maximal passive heating time was 120 min., 16 days of passive heating procedure... [to full text]

Temperatūra yra svarbi kūno raumenų funkcijai. Jai padidėjus greitėja raumenų susitraukimas ir atsipalaidavimas, didėja išvystomas galingumas, o per didelė raumenų temperatūra gali sumažinti fizinį darbingumą. Padidėjus kūno temperatūrai perduodami nerviniai impulsai smegenims: padidėja prakaitavimas, suaktyvėja kraujo apykaita, susilpnina raumenų veiklą, medžiagų apykaitą, ir tai sukelia nuovargį. Dideli temperatūros pokyčiai gali paveikti maksimaliąją izometrinę jėgą. Aukšta rektalinė temperatūra (daugiau kaip 40ºC) gali neigiamai paveikti centrinę nervų sistemą (CNS) ir šilumos išsiskyrimą iš organizmo. Hipertermija yra limituojantis veiksnys atliekant fizinį krūvį. Hipotezė: Manom, kad adaptacija pasyviai hipertermijai padidins raumens atsparumą nuovargiui ir izometrinio krūvio jėgą. Tyrimo tikslas - ištirti pasyvios hipertermijos poveikį moterų keturgalvio šlaunies raumens adaptacijai izometrinio krūvio metu ir širdies kraujotakos sistemai. Buvo tiriamos 6 sveikos, aktyviai nesportuojančios moterys, kurių amžiaus vidurkis 21,5 ± 1,6 m. Tyrimą sudarė du etapai. Pirmajame etame tiriamieji buvo tiriami esant įparastinės raumens būsenos temperatūrai. Antrajame tyrimo etape, kuris vyko dvi savaites, kai raumuo buvo pašildytas. Buvo matuojama moterų dešinės kojos, keturgalvio šlaunies raumens izometrinė maksimali valinga jėga bei nevalinga jėga, naudojant 1, 10, d10, 20, 50 100 Hz dažnių elektrostimuliaciją. Buvo stebimi širdies kraujagyslių sistemos pokyčiai pasyvios... [toliau žr. visą tekstą] / Temperature is important for muscle function. Muscle contraction and relaxation becomes quicker, development of power increasing as the temperature of the body raises. Immoderate temperature of the muscle, as a result, can decrease physical efficiency. Increased body temperature affects the nerve impulses, transmitted to brains, sweating level and also activates the blood circulation process. Hyperthermia is a limiting factor during the physical load on muscles. Large variations in temperature can cause changes in maximal voluntary force. High rectal temperature (higher than 40ºC) may negatively affect the central nervous system and the thermal emission of the body. Heating affects the skin and superficial layers of human body. Optimal temperature of water in which the muscle is placed during the study is about 45 ºC, because the higher temperature may cause the degradation processes of the proteins. Increased body temperature reduces the metabolism and the activity of the skeletal muscle, which causes the fatigue. Hypothesis: We think that the effect of passive hyperthermia increases the muscle resistance to the fatigue and the increase of the isometric strain. Objective of this research is to explore the effect of passive hyperthermia on women quadriceps adaptation to the isometric strain and cardiovascular system. The experimental group 6 females: age average 21.5 ± 1.6 y. The research consisted of two stages: During the first stage volunteers were tested in the basic... [to full text]

The clinical efficacy of chemotherapy in solid tumours is limited by systemic toxicity and the inability to deliver a cytotoxic concentration of anticancer drugs to all tumour cells. Temperature sensitive drug carriers provide a mechanism for triggering the rapid release of chemotherapeutic agents in a targeted region. Thermally mediated drug release also leverages the ability of hyperthermia to increase tumour blood flow, vessel permeability, and drug cytotoxicity. Drug release from thermosensitive liposome drug carriers in the tumour vasculature serves as a continuous intravascular infusion of free drug originating at the tumour site. However, localized drug release requires precise heating to improve drug delivery and efficacy in tumours while minimizing drug exposure in normal tissue. Focused ultrasound can noninvasively heat millimeter-sized regions deep within the body, and can be combined with MR thermometry for precise temperature control. This thesis describes the development of strategies to achieve localized hyperthermia using MRI-controlled focused ultrasound, for the purpose of image-guided heat-triggered drug release from thermosensitive drug carriers. First, a preclinical MRI-controlled focused ultrasound system was developed as a platform for studies of controlled hyperthermia and drug delivery in rabbits. The feasibility of using ultrasound hyperthermia to achieve localized doxorubicin release from thermosensitive liposomes was demonstrated in normal rabbit muscle. Second, strategies were described for using MR thermometry to control ultrasound heating at a muscle-bone interface based on MR temperature measurements in adjacent soft tissue, demonstrating localized drug delivery in adjacent muscle and bone marrow. Third, fluorescence microscopy was employed to demonstrate that increased overall drug accumulation in rabbit VX2 tumours corresponds to high levels of bioavailable drug reaching their active site in the nuclei of tumour cells. The results of this thesis demonstrate that image-guided drug delivery using thermosensitive liposomes and MRI-controlled focused ultrasound hyperthermia can be used to noninvasively achieve precisely localized drug deposition in soft tissue, at bone interfaces, and in solid tumours. Clinical application of this work could provide a noninvasive means of enhancing chemotherapy in a variety of solid tumours.

Submitted by Anna Carolina Telatin Tognolo null (carol.telatin@hotmail.com) on 2017-08-31T18:27:57Z No. of bitstreams: 1 Defesa_final Anna Carolina Telatin Tognolo.pdf: 2257425 bytes, checksum: 23469d70943bc2e64ecd46da99e37dc2 (MD5) / Approved for entry into archive by Luiz Galeffi (luizgaleffi@gmail.com) on 2017-09-01T14:39:51Z (GMT) No. of bitstreams: 1 tognolo_act_me_araiq.pdf: 2257425 bytes, checksum: 23469d70943bc2e64ecd46da99e37dc2 (MD5) / Made available in DSpace on 2017-09-01T14:39:51Z (GMT). No. of bitstreams: 1 tognolo_act_me_araiq.pdf: 2257425 bytes, checksum: 23469d70943bc2e64ecd46da99e37dc2 (MD5) Previous issue date: 2017-08-07 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O câncer é uma das doenças mais desafiadoras e não solucionadas até hoje na medicina moderna. Apesar das terapias padrões como radioterapia, quimioterapia, cirurgia ou combinações desses tratamentos serem efetivos, esses procedimentos apresentam diversos efeitos colaterais. Portanto, há uma vasta investigação por tratamentos alternativos a fim de diminuir os efeitos colaterais dessas terapias. Nanopartículas magnéticas de óxido de ferro (NP) modificadas com polímeros termossensíveis, vêm sendo desenvolvidas como um sistema de liberação controlada de fármaco e hipertermia magnética. Na presença de um campo magnético alternado externo (AC), esses sistemas são aquecidos induzindo a transição do polímero e, consequentemente, liberando o fármaco. Sendo assim, a proposta deste trabalho foi o desenvolvimento de um nanosistema terapêutico multifuncional. Nanopartículas superparamagnéticas de óxido de ferro foram sintetizadas, funcionalizadas com o alcoxisilano 3-mercaptopropil – trimetoxisilano (MPTS) e modificadas com o copolímero termossensível Poli(N-isopropilacrilamida-co-dimetilacrilamida), P(NIPAAm-co-DMAAm), para encapsulamento e liberação controlada do fármaco quimioterápico metotrexato e no tratamento por hipertermia magnética. A funcionalização com o MPTS foi confirmada por espectroscopia na região do infravermelho (FT-IR) e pela análise termogravimétrica (TGA). A copolimerização na superfície das nanopartículas foi confirmada pelas técnicas de FT-IR, medidas de potencial zeta, TGA e pela medida do diâmetro hidrodinâmico em função da temperatura. Determinou-se a baixa temperatura crítica de solução (LCST) do copolímero sintetizado, através da espectroscopia no UV-vis em função da temperatura. O valor de LCST determinado foi de 40,5 ºC e está dentro do esperado para aplicações biomédicas. Pela microscopia eletrônica de transmissão (MET), observou-se que as nanopartículas magnéticas apresentaram forma esférica e estreita distribuição de tamanho mesmo após serem modificadas com o copolímero. Os resultados obtidos na magnetermia, mostraram que as amostras aquecem quando são submetidas a um campo magnético externo, atingindo temperaturas esperadas para a hipertermia. E por fim, o encapsulamento e a liberação do metotrexato foram realizados com êxito, sendo que a liberação do fármaco acima da LCST do copolímero, apresentou melhor resultado quando comparado com a liberação abaixo dessa temperatura. / Nowadays, cancer is one of the biggest challenges in medicine. Besides the standards treatments such as chemotherapy, radiotherapy and surgery been affect, those procedures have several sides effects. In order to reduce the sides effects, there is extensive research for alternative treatments. Iron oxide magnetic nanoparticles (NP) modified with thermosensitive polymers, has been developed as a simultaneous system, for drug delivery and for magnetic hyperthermia. In the presence of an alternating magnetic field (AC), this system will be heated, inducing a phase transition of the thermoresponsive polymer and them, consequently releasing the drug inside the tumor cells. Therefore, the proposed of this work is the development of a therapeutic multifunctional nanosystem. Iron oxide magnetic nanoparticles were synthesized, functionalized with the alkoxysilane 3- mercaptopropyl trimethoxysilane (MPTS) and modified with the thermoresponsive copolymer P(NIPAAm-co-DMAAm), for the encapsulation and controlled release of the methotrexate (MTX) and for the magnetic hyperthermia. The surface modification of nanoparticles was monitored by Fourier Transform Infrared spectroscopy (FT-IR). TEM images showed nanoparticles with average size of 10 nm. The hydrodynamic diameter of the nanosystem as a function of the temperature was measured by dynamic light scattering and the hydrodynamic diameter for the P(NIPAAm-coDMAAm) surface modified nanoparticles, changes near 40 °C. Under an alternative AC, the nanosystem showed a high performance for hyperthermia treatment. Drug loading and release rate of methotrexate at different temperatures showed ideal behaviour for its application as drug delivery system.