A modular, human body-mimicking phantom with active thermoregulation capabilities for validation and verification of convective hyperthermia devices.

OBJECTIVES: This study aims to design and fabricate a modular phantom for hyperthermia applications, addressing interpatient variability in thermal regulation mechanisms like sweating rate, metabolic heat production, and blood redistribution. MATERIALS & METHODS: The phantom can be constructed in various weights and dimensions by connecting identical units. Each unit consists of an agar-based block, an ethyl cellulose-based top layer, a heat source, deep and superficial water circulation, and a sweating mechanism. Agar and ethyl cellulose gels mimic the thermal properties of human tissues and fat respectively. The blocks are wrapped in PVC foil to prevent water evaporation. A heating wire, coiled around an embedded aluminum tubing simulates metabolic heat production. A superficial water circulation mimics skin capillaries. A water pump ensures a steady flow rate throughout the tubing system. Sweat production is simulated using a water pump and perforated tubing. A programmed controller maintains core temperature in a normal operating mode and simulates an anesthetized patient in anesthesia mode. RESULTS: Temperature uniformity and regulation were assessed under varying environmental conditions. The phantom effectively regulated its core temperature at 37.0 °C +/- 0.7 °C with an ambient temperature ranging between 21 °C and 30 °C. Activating the water circulation reduced the maximum temperature gradient within the phantom from 4.70 °C to 1.92 °C. CONCLUSION: The versatile phantom successfully models heat exchange processes. Its thermal properties, dimensions, and heat exchange rates can be tuned to mimic different patient models. These are promising results as an effective tool for hyperthermia device validation and verification, representing human physiological responses.

Review of preclinical data on hyperthermia treatment in lymphomas and its potential for clinical application.

INTRODUCTION: Hyperthermia (HT) at temperatures between 39 °C and 44 °C is utilized as an adjunctive cancer therapy, serving as potent radio- and chemosensitizer. Its effectiveness in treating solid malignancies has been well established. This raises the question of whether HT can also benefit patients with nonsolid tumors, such as lymphomas. OBJECTIVE: To provide an overview of the current literature on research involving the use of HT in the treatment of lymphomas. MATERIAL AND METHODS: This systematic literature review was conducted following the PRISMA guidelines. For this purpose, a MeSH-term-defined literature search on MEDLINE (Pubmed) and Embase (Ovid) was conducted from June 25 to June 28, 2024. Included were in vitro studies on lymphoma cell lines and preclinical studies on animal models with lymphoma that were both treated with HT as monotherapy or HT in combination with another treatment, and studies on patients with lymphoma. Excluded were studies that used thermal ablation and hyperthermic perfusions. RESULTS: Thirty-nine studies were included, predominantly in vitro studies (n = 32) or studies on animal models (n = 5). The in vitro studies utilized HT either as monotherapy (n = 6), with substances that enhance HT efficacy (n = 18) or as a sensitizer for other treatments (n = 8). Additionally, two clinical case reports on the treatment of lymphoma patients were included. CONCLUSIONS: In vitro results suggest that HT can have anticancer effects on lymphoma cells and may enhance existing treatments. These findings are supported by in vivo studies and case reports. However, additional clinical data are needed before translation into the clinic can be implemented.

Management of Suspected α-Pyrrolidinoisohexanophenone (α-PiHP)-Related Hyperthermia in a Young Adult: A Case Report.

Synthetic cathinones, commonly known as "bath salts," have been increasingly implicated in severe health incidents. α-Pyrrolidinoisohexanophenone (α-PiHP) is one of the substances for which clinical data remain limited. In this article, we report a case of a 32-year-old male patient who ingested five grams of α-PiHP in a suicide attempt, resulting in hyperthermia and severe complications, including rhabdomyolysis and acute kidney injury. Despite the lack of confirmation for α-PiHP intoxication in toxicology screens, the patient's reported history was strongly suggestive. Considering a diagnostic uncertainty between serotonin syndrome and sympathomimetic toxidrome, and given the unavailability of cyproheptadine, dantrolene was administered to control the hyperthermia, resulting in a prompt and effective reduction in core body temperature. This case highlights the potential utility of dantrolene in treating hyperthermia induced by synthetic cathinones.

Device-Assisted Therapy in Non-Muscle-Invasive Bladder Cancer.

Intravesical therapy is a critical component in the management of non-muscle-invasive bladder cancer (NMIBC), as it reduces rates of disease recurrence and progression. However, the presence of physiologic barriers in the urothelium reduces the penetration and distribution of intravesical chemotherapy, thereby limiting the therapeutic potential. Much progress to overcome this challenge has been made in the realm of intravesical device-assisted therapy. Novel device-assisted treatments include hyperthermia, the radiofrequency-induced thermochemotherapy effect, electromotive drug administration, and implantable drug delivery systems. Notably, chemotherapy enhanced by these device-assisted systems has shown improved oncologic efficacy relative to standard intravesical chemotherapy and comparable outcomes relative to Bacillus Calmette-Guérin (BCG) therapy in patients with intermediate- or high-risk NMIBC. Recent studies also support the utility of device-assisted therapy as a salvage treatment option in patients with BCG-unresponsive disease. Ongoing randomized controlled trials and prospective investigations will further help clarify indications and long-term safety outcomes of these treatment modalities in NMIBC. Herein, we present a comprehensive review of device-assisted therapies and discuss their clinical utilities for the management of NMIBC in the modern era.

Hyperthermia and biological investigation of a novel magnetic nanobiocomposite based on acacia gum-silk fibroin hydrogel embedded with poly vinyl alcohol.

The design and synthesis of biocompatible nanostructures for biomedical applications are considered vital challenges. Herein, a nanobiocomposite based on acacia hydrogel, natural silk fibroin protein, and synthetic protein fibers of polyvinyl alcohol was fabricated and magnetized with iron oxide nanoparticles (Fe3O4 MNPs). The structural properties of the hybrid nanobiocomposite were investigated by essential analyses such as Fourier Transform Infrared Spectrometer (FTIR), Field emission scanning electron microscopy (FE-SEM), and X-ray powder diffraction)XRD(analyses, Thermogravimetric and Differential thermogravimetric analysis (TGA-DTG), Vibrating-sample magnetometry (VSM), and Energy Dispersive X-Ray Analysis (EDX). The biological activities and functional properties of the prepared magnetic nanobiocomposite were studied. Results proved that this nanobiocomposite is non-toxic to the healthy HEK293T cell line. In addition, the synthesized nanobiocomposite showed an approximately 22 % reduction in cell viability of BT549 cells after 72 h. All results confirmed the anti-cancer properties of nanobiocomposite against breast cancer cell lines. Therefore, the prepared nanobiocomposite is an excellent material that can use for in-vivo application. Finally, the hyperthermia application was evaluated for this nanobiocomposite. The SAR was measured 93.08 (W/g) at 100 kHz.

Innovative cancer therapy: Unleashing the potential of macromolecule-loaded mesoporous bioactive glasses for precision diagnosis and treatment.

Cancer continues to pose a formidable threat, claiming millions of lives annually. A beacon of hope in this battle lies in the realm of bioactive glasses, which have undergone a remarkable evolution over the past five decades. Among these, mesoporous bioactive glasses (MBGs) emerge as a dynamic subset endowed with customizable attributes such as high surface area and porosity. While holding immense promise for cancer care, the full clinical potential of MBGs remains largely unexplored. This review delves into the cutting-edge advancements in MBG technology, illuminating their pivotal role in cancer management - spanning from early detection to targeted therapeutic interventions like photothermal and photodynamic treatments. Furthermore, the molecular mechanisms underpinning MBGs' anticancer properties are elucidated, alongside an exploration of existing limitations in their application. Through this comprehensive synthesis, the significance of MBGs in revolutionizing cancer therapy is underscored, underscoring the urgent need for continued research to unlock their full potential in reshaping the landscape of cancer care.

Tuning the physical properties of ternary alloys (NiCuCo) for in vitro magnetic hyperthermia: experimental and theoretical investigation.

Most of published research on magnetic hyperthermia focused on iron oxides, ferrites, and binary alloy nanostructures, while the ternary alloys attracted much limited interest. Herein, we prepared NiCuCo ternary alloy nanocomposites with variable compositions by mechanical alloying. Physical properties were fully characterized by XRD, Rietveld analysis, XPS, SEM/EDX, TEM, ZFC/FC and H-M loops. DFT calculations were used to confirm the experimental results in terms of structure and magnetism. The results showed that the fabricated nanoalloys are face centered cubic (FCC) with average core sizes of 9-40 nm and behave as superparamagnetic with saturation in the range 4.67-42.63 emu/g. Langevin fitting corroborated the superparamagnetic behavior, while law of approach to saturation (LAS) was used to calculate the magnetic anisotropy constants. Heating effciencies were performed under an alternating magnetic field (AMF, H0 = 170 Oe and f = 332.5 kHz), and specific absorption rate (SAR) values were determined. The highest magnetic saturation (Ms), heating potentials, and SAR values were attained for Ni35Cu30Co35 containing the lowest Cu but highest Ni and Co percentages, and the least for Ni15Cu70Co15. Importantly, the nanoalloys reached the required temperatures for magnetic hyperthermia (42 °C) in relatively short times. We also showed that heat dissipiation can be simply tuned by changing many parameters such as concentration, field amplitude, and frequency. Finally, cytotoxicity viability assays against two different breast cancer cell lines treated with Ni25Cu50Co25 nanoalloy in the presence and absence of AMF were investigated. No significant decrease in cancer cell viability was observed in the absence of AMF. When tested against tumorigenic KAIMRC2 breast cancer cells under AMF, the NiCuCo nanoalloy was found to be highly potent to the cells (~ 2-fold enhancement), killing almost all the cells in short times (20 min) and clinically-safe AC magnetic fields. These findings strongly suggest that the as-prepared ternary NiCuCo nanoalloys hold great promise for potential magnetically-triggered cancer hyperthermia.

A Case Report of Long-Term Survival Achieved by Nivolumab and Hyperthermia With Multiple Local Therapies for the Peritoneal Dissemination of Gastric Cancer.

A 60-year-old male with recurrent metastatic gastric cancer achieved long-term survival with nivolumab, hyperthermia, and local multisite therapy. The patient had a history of multiple relapses despite receiving standard treatment. After the failure of multiple lines of chemotherapy, nivolumab and hyperthermia were initiated. During this combination therapy, local treatments including surgery and radiation therapy were administered to treat the progressive disease. Remarkably, the patient achieved more than five years of overall survival time after starting nivolumab and external repeated hyperthermia with local therapies and has shown no measurable disease on imaging for the past 24 months. This case suggests that a combination of nivolumab, hyperthermia, and local therapies may offer a potential therapeutic strategy for patients with advanced gastric cancer.

Limb salvage using radical combined hyperthermia and radiotherapy for myxofibrosarcoma of the lower leg in an elderly patient.

Soft tissue sarcomas account for only 1.5% of malignant tumors in adults and are therefore challenging to treat. We present a case of myxofibrosarcoma of the lower leg in an 88-year-old woman who successfully responded to combined hyperthermia and radiotherapy. We proposed a below-knee amputation because of the spread of the lesion, but the patient opted for hyperthermia with radiotherapy. One and a half years later, the tumor partially regrew, and the regrown mass was resected with an R0 margin. Unfortunately, the patient developed a surgical site infection immediately after the resection, and a skin ulcer formed. It took about 2 years for conservative treatment to result in complete ulcer epithelization. The patient has been ambulant, and has not experienced any symptoms of local recurrence or metastasis in the two and a half years since the surgery. Although adverse events related to combined hyperthermia and radiotherapy, such as delayed wound healing, should be considered, it could be an option for the treatment of localized soft-tissue sarcoma, especially in elderly patients.

Neoadjuvant chemoradiotherapy in combination with deep regional hyperthermia followed by surgery for rectal cancer: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Combining chemoradiotherapy (CRT) with deep regional hyperthermia (HT) shows promise for enhancing clinical outcomes in selected rectal cancer patients. This study aimed to integrate the evidence and evaluate the efficacy of this combined treatment approach. MATERIALS AND METHODS: A systematic search of the PubMed, Scopus, and Mendeley databases was performed. This review was conducted according to the PRISMA guidelines. The quality of studies was evaluated using the Newcastle-Ottawa scale (NOS). Random-effects meta-analyses (DerSimonian and Laird) were performed. The primary outcome was pathological complete response (pCR), and secondary endpoints were overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and toxicity. RESULTS: In total, 12 studies were included, mostly of moderate quality. Patients with locally advanced rectal cancer (LARC; n = 760) and locally recurrent rectal cancer (LRRC; n = 22) were eligible. The pooled pCR rate was 19% (95% confidence interval [CI]: 16-22%) among all 782 patients and 19% (95%CI:16-23%) among 760 LARC patients. Due to significant study heterogeneity, survival outcomes were pooled by excluding LRRC patients. The pooled 5­year OS rate among 433 LARC patients was 87% (95%CI: 83-90%). The pooled 5­year DFS and LRFS in LARC patients were 75% (95%CI: 70-80%) and 95% (95%CI: 92-97%), respectively. There was a lack of consistent reporting of HT treatment parameters and toxicity symptoms among the studies. CONCLUSION: The collective clinical evidence showed that neoadjuvant CRT combined with HT in rectal cancer patients is feasible, with a 19% pCR rate and excellent survival outcomes in long term follow-up.

Combination of magnetic hyperthermia and gene therapy for breast cancer.

This study presented a novel breast cancer therapy model that uses magnetic field-controlled heating to trigger gene expression in cancer cells. We created silica- and amine-modified superparamagnetic nanoparticles (MSNP-NH2) to carry genes and release heat under an alternating current (AC) magnetic field. The heat-inducible expression plasmid (pHSP-Azu) was designed to encode anti-cancer azurin and was delivered by magnetofection. MCF-7 cells demonstrated over 93% cell viability and 12% transfection efficiency when exposed to 75 µg/ml of MSNP-NH2, 3 µg of DNA, and PEI at a 0.75 PEI/DNA ratio (w: w), unlike non-tumorigenic cells (MCF-10 A). Magnetic hyperthermia (MHT) increased azurin expression by heat induction, leading to cell death in dual ways. The combination of MHT and heat-regulated azurin expression induced cell death, specifically in cancer cells, while having negligible effects on MCF-10 A cells. The proposed strategy clearly shows that simultaneous use of MHT and MHT-induced azurin gene expression may selectively target and kill cancer cells, offering a promising direction for cancer therapy.

Comparisons of computer simulations and experimental data for capacitive hyperthermia using different split-phantoms.

INTRODUCTION: Several positive clinical trials have demonstrated that capacitive hyperthermia (CHT) improves the effectiveness of radiation therapy for the treatment of various cancer entities. However, the ability of CHT to induce significant heating throughout the body is under debate. OBJECTIVES: To perform a pilot study involving comparisons of computer simulations and experimental data using different split-phantoms to validate hyperthermia treatment modeling for pre-planning for a clinical CHT system and to investigate the feasibility of split-phantom measurements in capacitive hyperthermia. MATERIALS AND METHODS: The CHT system EHY-2030 (Oncotherm, Budapest, Hungary) was used. The system provides two electrode sizes, but only the smaller electrode, indicated as D200 electrode, was investigated in this pilot study. Horizontally and vertically splittable, different multi-slice phantoms with dielectric material properties simulating muscle and electrically low conductive fat were produced and heated. During the heating procedure, temperature-time curves were measured, and thermal images were captured. Specific absorption rate values were derived from the temperature rise (TR) values. Concomitantly, computer field simulations utilizing a detailed CAD-based model of the CHT system were performed using the simulation platform Sim4Life and compared with measurements. RESULTS: For the investigated electrode D200 the system power of 75 W was applied, which is half of the maximum power of 150 W and lies in the range of usual values for this electrode applied in patient treatments in our clinic. For 75 W, a heating of 3.6 °C in 6 min in a depth of 1 cm in an agar-based, muscle tissue-equivalent phantom was achieved. The addition of a 1 cm thick, synthetic, low dielectric fat layer reduced the TR up until a depth of 8.5 cm by on average around 38% (from 8.5 cm onwards the absolute local TR is similar, deviations are ≤0.1 °C). In terms of point-to-point absolute SAR comparison (without any normalization), up to a depth of 11 cm in the phantoms central vertical plot, the simulation differs from the measured TR points by on average 25% (ranging from 7% to 36%) for the homogeneous phantom and by on average 43% (ranging from 26% to 60%) for the inhomogeneous phantom. CONCLUSION: Computer simulations and experimental data were compared for the CHT system EHY-2030 using the D200 electrode, applying a thermal imaging technique for different vertically splittable phantoms. This pilot study data can be used as a guidance regarding the expected heating for this commonly used electrode size but also to further elucidate the significance of non-thermal anticancer effects. Further studies are needed for different sizes and geometries of electrodes and phantoms.

Synergistic effects of combined hyperthermia and electric fields treatment in non-small cell lung-cancer (NSCLC) cell lines.

PURPOSE: Lung cancer remains a leading cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) being particularly challenging due to poor survival rates, emphasizing the need for new treatments. This study examined the therapeutic effects of combining hyperthermia (HT) with tumor-treating electric fields (TTF) in NSCLC. METHODS: Cells were exposed to four different conditions: hyperthermia at 42 °C for 30 min, electric fields at 150 kHz and 0.8 V/cm for 24 h, a combination of both treatments, or no treatment (control). Cell proliferation was measured using WST and colony-formation assays, while apoptosis, DNA damage, and repair protein levels were analyzed via Western blotting. Metastatic potential was evaluated with a transwell assay, and cell migration was assessed using the wound-healing assay. RESULTS: The combination therapy significantly inhibited colony formation and reduced cell migration and invasion more effectively than individual treatments. The combined treatment also enhanced apoptosis, as indicated by increased cleaved-PARP and Annexin V levels. In addition, the DNA-damage marker γ-H2AX was elevated, while BRCA1, a protein involved in DNA repair, was significantly downregulated compared to the individual treatments. CONCLUSIONS: These results suggest that the enhanced anticancer effects of HT and TTF are due to increased DNA damage and suppression of DNA-repair mechanisms, highlighting the potential of this combination therapy for NSCLC treatment.

Comprehensive succinylome analyses reveal that hyperthermia upregulates lysine succinylation of annexin A2 by downregulating sirtuin7 in human keratinocytes.

Background and Objectives: Local hyperthermia at 44°C can clear multiple human papillomavirus (HPV)-infected skin lesions (warts) by targeting a single lesion, which is considered as a success of inducing antiviral immunity in the human body. However, approximately 30% of the patients had a lower response to this intervention. To identify novel molecular targets for anti-HPV immunity induction to improve local hyperthermia efficacy, we conducted a lysine succinylome assay in HaCaT cells (subjected to 44°C and 37°C water baths for 30 min). Methods: The succinylome analysis was conducted on HaCaT subjected to 44°C and 37°C water bath for 30 min using antibody affinity enrichment together with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results were validated by western blot (WB), immunoprecipitation (IP), and co-immunoprecipitation (Co-IP). Then, bioinformatic analysis including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, motif characterization, secondary structure, and protein-protein interaction (PPI) was performed. Results: A total of 119 proteins with 197 succinylated sites were upregulated in 44°C-treated HaCaT cells. GO annotation demonstrated that differential proteins were involved in the immune system process and viral transcription. Succinylation was significantly upregulated in annexin A2. We found that hyperthermia upregulated the succinylated level of global proteins in HaCaT cells by downregulating the desuccinylase sirtuin7 (SIRT7), which can interact with annexin A2. Conclusions: Taken together, these data indicated that succinylation of annexin A2 may serve as a new drug target, which could be intervened in combination with local hyperthermia for better treatment of cutaneous warts.

The Impact of Photobiomodulation Therapy on Enhancing Spermatogenesis and Blood-Testis Barrier Integrity in Adult Male Mice Subjected to Scrotal Hyperthermia.

Introduction: Unhealthy lifestyle choices such as alcohol, chemicals, and heat stress can worsen male infertility. Heat stress can cause damage to the essential structure known as the blood-testis barrier (BTB). Photobiomodulation therapy (PBMT) has been employed in various studies to enhance sperm quality in individuals with genital inflammatory conditions in recent times. The current research sought to study how laser therapy affects spermatogenesis and the structure of the BTB in a mouse model of scrotal heat exposure. Methods: Thirty adult male NMRI mice, 8 weeks old, were divided into three groups: Control, Hyperthermia, and Hyperthermia+Laser 0.03 J/cm2. The animals in the hyperthermia group had their testicles exposed to water at 43 °C for 20 minutes five times every other day. Then, the testicles were exposed to laser radiation every other day for 35 days, lasting 3 minutes each time, with an energy density of 0.03 J/cm2. Animals were sacrificed, and sperm parameters, reactive oxygen species (ROS) and glutathione (GSH) levels, stereological parameters, and gene expression were assessed in the end. Results: The study showed that PBMT can significantly enhance sperm quality, quantity of spermatogenic cells, testicular volume, levels of ROS and GSH, and gene expression related to the blood-testis barrier. Conclusion: Currently, PBMT is a novel approach for addressing male infertility by preserving the integrity of the BTB in Sertoli cells, which in turn supports the growth and specialization of germ cells.

Anesthetic Challenges of a Patient With Limb-Girdle Muscular Dystrophy in a Patient With Colon Cancer.

Limb-girdle muscular dystrophy (LGMD) presents a unique challenge for anesthesiologists because of the potential complications related to surgery and anesthesia. This is a case of a 55-year-old male with colon cancer and a history of LGMD, who underwent a low anterior resection colectomy under general anesthesia. Because of the pathogenic variants in the RYR1 gene implicated in various congenital myopathies, we review clinical concerns associated with LGMD and describe the anesthetic management of our patient with LGMD and a potentially difficult airway.

Protective impact of Betanin against noise and scrotal hyperthermia on testicular toxicity in Wistar rat: Role of apoptosis, oxidative stress and inflammation.

The heat exposure and white noise can induce damage on reproductive organs. The main objective of this study is to observe, if betanin administration could ameliorate oxidative stress, apoptosis and inflammation in testis of rodents following noise and scrotal hyperthermia exposure. Wistar rats were divided into 6 groups; control, betanin, noise, hyperthermia and two treatment groups. Scrotal hyperthermia model was performed by heat exposure of rat testicular (43 °C) for 15 min and 3 times per weeks for 14 days. Noise induction model was done following exposure of rats with 100-dB noise level for 14 days and 8 h daily similar to real exposure condition in human. Betanin was administrated at the sub-effective dose (15 mg/kg) by gavage route for 4 weeks (5 times a week) to male rats. The animals were euthanized and testis were dissected and stored at -80 °C. Then, the oxidative stress biomarkers (MDA and GSH), apoptosis (cytochrome c & Annexin V), and inflammatory cytokines (TNF-α & IL-6) were measured by the real time polymerase chain reaction (RT-PCR) of testis collected samples. The data output demonstrates the impact of noise and hyperthermia in testicular toxicity induction by mitigating oxidative damage, apoptosis and inflammatory mediators. Following treatment with 15 mg/kg per day of betanin, lipid peroxidation and GSH content have been modulated, and TNF-α and IL-6 gene expression has been declined. Our results revealed that in Wistar rats, betanin displays protective effects against noise and scrotal hyperthermia-induced acute testicular toxicity through the inhibition of oxidative stress, apoptosis, and inflammation.

Real-time non-invasive control of ultrasound hyperthermia using high-frequency ultrasonic backscattered energy inex vivotissue andin vivoanimal studies.

Objective.A reliable, calibrated, non-invasive thermometry method is essential for thermal therapies to monitor and control the treatment. Ultrasound (US) is an effective thermometry modality due to its relatively high sensitivity to temperature changes, and fast data acquisition and processing capabilities.Approach.In this work, the change in backscattered energy (CBE) was used to control the tissue temperature non-invasively using a real-time proportional-integral-derivative (PID) controller. A clinical high-frequency US scanner was used to acquire radio-frequency echo data fromex vivoporcine tissue samples andin vivomice hind leg tissue while the tissue was treated with mild hyperthermia by a focused US applicator. The PID controller maintained the focal temperature at approximately 40 °C for about 4 min.Main results.The results show that the US thermometry based on CBE estimated by a high-frequency US scanner can produce 2D temperature maps of a localized heating region and to estimate the focal temperature during mild hyperthermia treatments. The CBE estimated temperature varied by an average of ±0.85 °C and ±0.97 °C, compared to a calibrated thermocouple, inex vivoandin vivostudies, respectively. The mean absolute deviations of CBE thermometry during the controlled hyperthermia treatment were ±0.45 °C and ±0.54 °C inex vivoandin vivo,respectively.Significance.It is concluded that non-invasive US thermometry via backscattered energies at high frequencies can be used for real-time monitoring and control of hyperthermia treatments with acceptable accuracy. This provides a foundation for an US mediated drug delivery system.

Mitochondrial-uncoupling nanomedicine for self-heating and immunometabolism regulation in cancer cells.

Developing endogenous hyperthermia offers a promising strategy to address challenges with current exogenous hyperthermia techniques in clinics. Herein, a CD44-targeted and thermal-responsive nanocarrier was developed for the simultaneous delivery of 2,4-dinitrophenol and syrosingopine. The objective was to induce endogenous hyperthermia and regulate immunometabolism, ultimately augmenting anti-tumour immune responses. Dinitrophenol as mitochondrial uncoupler can convert electrochemical potential energy of inner mitochondrial membrane into heat, facilitating endogenous hyperthermia. Meanwhile, syrosingopine not only inhibits excessive lactate efflux caused by dinitrophenol but also downregulates tumour cell glycolysis, thus alleviating immunosuppression and heat shock protein (HSP)-dependent thermo-resistance through immunometabolism regulation. The synergistic effects of endogenous hyperthermia and immunometabolism regulation by this nanomedicine have potential to enhance tumor immunogenicity, reshape the tumour immune microenvironment, and effectively suppress the growth of subcutaneous tumours and patient-derived organoids in triple-negative breast cancer. Therefore, the endogenous hyperthermia strategy developed in this study would revolutionize hyperthermia for cancer treatment.

Effect of magnetic anisotropy and interaction on spatial focused hyperthermia for rotating and oscillating fields.

The behavior of magnetic nanoparticles in a time-varying magnetic field has several practical applications. One of these is hyperthermia used in the treatment of cancer. The nanoparticles injected in the tumor cells release the energy absorbed from the time dependent external magnetic field in the form of heat to its environment in a well-localized way. The aim of the research in this area is to maximize the amount of the dissipated energy. Using a combination of an oscillating and static magnetic field, this dissipated energy can be more focused in space. In this article, we investigated whether this spatial focusing is also present using a rotating and static field together. Furthermore, we investigated the effects of anisotropy and interaction between nanoparticles on this spatial focusing effect using the jump-diffusion model for Néel relaxation in both cases. This kinetic Monte Carlo (MC) method was validated and compared with the stochastic Landau-Lifshitz-Gilbert (SLLG) equation based model. We have shown that the spatial focusing effect is also present for these non-idealized experimentally realizable cases. Also, the effect of rotating magnetic field on magnetic nanoparticles was not investigated in kinetic Monte Carlo simulations before.