Intelligent Size-Switchable Iron Carbide-Based Nanocapsules with Cascade Delivery Capacity for Hyperthermia-Enhanced Deep Tumor Ferroptosis.

The ferroptosis pathway is recognized as an essential strategy for tumor treatment. However, killing tumor cells in deep tumor regions with ferroptosis agents is still challenging because of distinct size requirements for intratumoral accumulation and deep tumor penetration. Herein, intelligent nanocapsules with size-switchable capability that responds to acid/hyperthermia stimulation to achieve deep tumor ferroptosis are developed. These nanocapsules are constructed using poly(lactic-co-glycolic) acid and Pluronic F127 as carrier materials, with Au-Fe2 C Janus nanoparticles serving as photothermal and ferroptosis agents, and sorafenib (SRF) as the ferroptosis enhancer. The PFP@Au-Fe2 C-SRF nanocapsules, designed with an appropriate size, exhibit superior intratumoral accumulation compared to free Au-Fe2 C nanoparticles, as evidenced by photoacoustic and magnetic resonance imaging. These nanocapsules can degrade within the acidic tumor microenvironment when subjected to laser irradiation, releasing free Au-Fe2 C nanoparticles. This enables them to penetrate deep into tumor regions and disrupt intracellular redox balance. Under the guidance of imaging, these PFP@Au-Fe2 C-SRF nanocapsules effectively inhibit tumor growth when exposed to laser irradiation, capitalizing on the synergistic photothermal and ferroptosis effects. This study presents an intelligent formulation based on iron carbide for achieving deep tumor ferroptosis through size-switchable cascade delivery, thereby advancing the comprehension of ferroptosis in the context of tumor theranostics.

Influence of different heat transfer models on therapeutic temperature prediction and heat-induced damage during magnetic hyperthermia.

Magnetic hyperthermia regulates the therapeutic temperature within a specific range to damage malignant cells after exposing the magnetic nanoparticles inside tumor tissue to an alternating magnetic field. The therapeutic temperature of living tissues can be generally predicted using Pennes' bio-heat equation after ignoring both the inhomogeneity of biological structure and the microstructural responses. Although various of the bio-heat transfer models proposed in literature fix these shortages, there is still a lack of a comprehensive report on investigating the discrepancy for different models when applied in the magnetic hyperthermia context. This study compares four different bio-heat equations in terms of the therapeutic temperature distribution and the heat-induced damage situation for a proposed geometric model, which is established based on computed tomography images of a tumor bearing mouse. The therapeutic temperature is also used as an index to evaluate the effect of two key relaxation times for the phase lag behavior on bio-heat transfer. Moreover, this work evaluates the effects of two blood perfusion rates on both the treatment temperature and the cumulative equivalent heating minutes at 43 °C. Numerical analysis results reveal that relaxation times for phase-lag behavior as well as the porosity for living tissues directly affect the therapeutic temperature variation and ultimately the thermal damage for the malignant tissue during magnetic hyperthermia. The dual-phase-lag equation can be converted into Pennes' equation and simple-phase-lag equation when relaxation times meet specific conditions during the process of heat transfer. In addition, different blood perfusion rates can result in an amplitude discrepancy for treatment temperature, but this parameter does not change the characteristics of thermal propagation during therapy.

Photonic Hyperthermia Synergizes with Immune-Activators to Augment Tumor-Localized Immunotherapy.

Photothermal immunotherapy, the combination of photothermal hyperthermia and immunotherapy, is a noninvasive and desirable therapeutic strategy to address the deficiency of traditional photothermal ablation for tumor treatment. However, insufficient T-cell activation following photothermal treatment is a bottleneck to achieve satisfactory therapeutic effectiveness. In this work, a multifunctional nanoplatform is rationally designed and engineered on the basis of polypyrrole-based magnetic nanomedicine modified by T-cell activators of anti-CD3 and anti-CD28 monoclonal antibodies, which have achieved robust near infrared laser-triggered photothermal ablation and long-lasting T-cell activation, realizing diagnostic imaging-guided immunosuppressive tumor microenvironment regulation following photothermal hyperthermia by reinvigorating tumor-infiltrating lymphocytes. By virtue of high-efficient immunogenic cell death and dendritic cell maturation combined with T-cell activation, this nanosystem markedly restrains primary and abscopal tumors as well as metastatic tumors with negligible side effects in vivo, exerting the specific function for suppressing tumor recurrence and metastasis by establishing a long-term memory immune response.

Optimization of hyperthermia process applied to cancer treatment using multi-objective optimization differential evolution.

Due to the number of cancer cases diagnosed each year and the fatality rate resulting from some more severe types, the improvement of less invasive and more efficient treatment techniques is of great importance. In this context, hyperthermia is a medical procedure in which the tumor region is heated by using an applicator for a certain period, aiming to destroy pathological cells. Computational models can be used to simulate the heating effect of tumors and adjacent cells. In general, the solution to an optimization problem considering factors such as heating temperature, applicator position, and the time in which the region will be subjected to heating can provide important information about the procedure. Traditionally, this type of problem has been addressed in a single objective context, focusing on minimizing the destruction of adjacent healthy tissue considering the area of the applicator constant. Our fundamental objective is to propose a multi-objective design problem considering the minimization of the area subject to the procedure and the time required for the process of hyperthermia in a breast cancer treatment. The problem is constrained by the degree of tissue destruction and by a partial differential equation that describes the phenomenon of heat transfer in both healthy and tumor tissues. The results obtained demonstrate that a point with a good compromise between the objectives can be chosen in such a way that a particular strategy can be defined for each patient.

Synergistic effect of tumor chemo-immunotherapy induced by leukocyte-hitchhiking thermal-sensitive micelles.

Some specific chemotherapeutic drugs are able to enhance tumor immunogenicity and facilitate antitumor immunity by inducing immunogenic cell death (ICD). However, tumor immunosuppression induced by the adenosine pathway hampers this effect. In this study, E-selectin-modified thermal-sensitive micelles are designed to co-deliver a chemotherapeutic drug (doxorubicin, DOX) and an A2A adenosine receptor antagonist (SCH 58261), which simultaneously exhibit chemo-immunotherapeutic effects when applied with microwave irradiation. After intravenous injection, the fabricated micelles effectively adhere to the surface of leukocytes in peripheral blood mediated by E-selectin, and thereby hitchhiking with leukocytes to achieve a higher accumulation at the tumor site. Further, local microwave irradiation is applied to induce hyperthermia and accelerates the release rate of drugs from micelles. Rapidly released DOX induces tumor ICD and elicits tumor-specific immunity, while SCH 58261 alleviates immunosuppression caused by the adenosine pathway, further enhancing DOX-induced antitumor immunity. In conclusion, this study presents a strategy to increase the tumor accumulation of drugs by hitchhiking with leukocytes, and the synergistic strategy of chemo-immunotherapy not only effectively arrested primary tumor growth, but also exhibited superior effects in terms of antimetastasis, antirecurrence and antirechallenge.

Manejo não farmacológico da febre e hipertermia da criança: revisão integrativa / Manejo no farmacológico de la fiebre e hipertermia en niños: revisión integradora / Non-pharmacological fever and hyperthermia management in children: an integrative review

Resumo Objetivo: Identificar as intervenções não farmacológicos para febre e hipertermia em crianças indicados na literatura científica. Métodos: Trata-se de uma revisão integrativa da literatura realizada nas bases de dados Lilacs, PubMed e CINAHL e as bibliotecas COCHRANE e SciELO. Foram incluídos artigos que abordassem as intervenções não farmacológicas para febre e hipertermia, publicados em português e inglês, no período de 2000 a 2019. Resultados: A amostra foi constituída por 27 artigos, que foram agrupados, conforme suas similaridades, em sete categorias. As intervenções utilizadas foram: banhos; compressas mornas; sponging ; incentivo à ingestão de líquidos; bolsas de gelo e cobertores refrigerados; e, por último, a categoria ventilação do ambiente. Observaram-se diferentes intervenções no manejo não farmacológico de febre e hipertermia. Conclusão: A prática de medidas não farmacológicas isoladamente não é recomendada para o tratamento de febre em crianças, exceto as intervenções que auxiliem nas respostas fisiológicas do corpo. Os resultados ressaltam a recomendação da realização de novas pesquisas que redundem em evidências para fundamentar o melhor cuidado do enfermeiro pediatra à criança com febre.

Resumen Objetivo: Identificar las intervenciones no farmacológicas para la fiebre e hipertermia en niños recomendadas en la literatura científica. Métodos: Se trata de una revisión integradora de la literatura realizada en las bases de datos Lilacs, PubMed y CINAHL y las bibliotecas COCHRANE y SciELO. Se incluyeron artículos que abordaran las intervenciones no farmacológicas para la fiebre e hipertermia, publicados en portugués e inglés, en el período de 2000 a 2019. Resultados: La muestra estuvo compuesta por 27 artículos, que fueron agrupados en siete categorías según sus similitudes. Las intervenciones utilizadas fueron: baños, compresas tibias, sponging , incentivo a la ingesta de líquidos, bolsas de hielo y mantas refrigeradas y, por último, la categoría ventilación del ambiente. Se observaron diferentes intervenciones en el manejo no farmacológico de la fiebre e hipertermia. Conclusión: No se recomienda la práctica de medidas no farmacológicas de forma aislada para tratar la fiebre en niños, excepto las intervenciones que ayuden a las respuestas fisiológicas del cuerpo. Los resultados resaltan la recomendación de realizar nuevos estudios que tengan como resultado evidencias para fundamentar un mejor cuidado del enfermero pediatra a niños con fiebre.

Abstract Objective: To identify non-pharmacological interventions for fever and hyperthermia in children indicated in the scientific literature. Methods: an integrative literature review carried out in the LILACS, PubMed and CINAHL databases and in the COCHRANE and SciELO libraries. Articles that addressed non-pharmacological interventions for fever and hyperthermia, published in Portuguese and English, from 2000 to 2019, have been included. Results: The sample consisted of 27 articles, which were grouped, according to their similarities, into seven categories. The interventions used were baths, warm compresses, sponging, encouraging fluid intake, ice packs, cooled blankets, and room ventilation. Different interventions were observed in non-pharmacological fever and hyperthermia management. Conclusion: Practicing non-pharmacological measures alone is not recommended for fever treatment in children, except for interventions that assist in the physiological responses of the body. The results highlight the recommendation of conducting further research that results in evidence to support the best care provided by pediatric nurses to children with fever.

Deep brain stimulation as a possible treatment of hyperthermia in patients with serotonin syndrome.

Maintaining a body temperature within a narrow range is vital for the survival of all mammals, including humans. With the help of optogenetics, a better understanding of the thermoregulatory organs and pathways is achieved. Optogenetic activation of the GABAergic neurons in the ventral part of the lateral preoptic nucleus (VLPO) leads to decrease in the body temperature. On the other hand, number of drugs could alter the thermoregulatory balance, leading to a hyperthermic state, such as serotonin syndrome (SS). SS is a potentially life-threatening clinical condition that occurs as a result of a drug-induced increase in the intrasynaptic serotonin (5-hydroxytryptamine, 5-HT) levels due to overdose of a single drug or due to interaction between two or more drugs with serotonergic mechanism of action. In this hypothesis, we propose a novel method for the treatment of hyperthermia, a core clinical sign of serotonin syndrome, through deep brain stimulation (DBS). An electrode is stereotactically placed in the VLPO, which may lead to reduction of the core body temperature. If proven effective, this technique should be left as a salvage method for reduction of hyperthermia, where the drug treatment is insufficient or ineffective. This technique could be used for the treatment of other syndromes, where hyperthermia takes a central place, including malignant hyperthermia, neuroleptic malignant syndrome, etc. DBS, on the other hand, could be used alone to induce hyperthermia in patients with malignant diseases. Hyperthermia improves the immune response, improves the drug penetration and stop the repair of already damaged tumor cells after chemotherapy or radiotherapy.

Quality indicators for hyperthermia treatment: Italian survey analysis.

AIM: Nowadays, no Quality Indicators (QI) have been proposed for Hyperthermia treatments. Starting from radiotherapy experience, the aim of this work is to adapt radiotherapy indicators to Hyperthermia and to propose a new specific set of QI in Hyperthermia field. MATERIAL AND METHODS: At first, radiotherapy quality indicators published in literature have been adapted to hyperthermia setting. Moreover, new specific indicators for the treatment of hyperthermia have been defined. To obtain the standard reference values of quality indicators, a questionnaire was sent to 7 Italian hyperthermia Institutes with a list of questions on physical and clinical hyperthermia treatment in order to highlight the different therapeutic approaches. RESULTS: Three structure, five process and two outcome QI were selected. It has been possible to adapt seven indicators from radiotherapy, while three indicators have been defined as new specific indicators for hyperthermia. Average values used as standard reference values have been obtained and proposed. CONCLUSION: The survey performed on 7 Italian centres allowed to derive the standard reference value for each indicator. The proposed indicators are available to be investigated and applied by a larger number of Institutes in which hyperthermia treatment is performed in order to monitor the operational procedures and to confirm or modify the reference standard value derived for each indicator.