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Low-melting-point polymeric nanoshells for thermal-triggered drug release under hyperthermia condition

Dabbagh A, Mahmoodian R, Abdullah BJ, Abdullah H, Hamdi M, Abu Kasim NH

Int J Hyperthermia, 2015;31(8):920-9.
PMID: 26670340 DOI: 10.3109/02656736.2015.1094147

The aim of this paper was to synthesise core-shell nanostructures comprised of mesoporous silica core and a low melting-point polyethylene glycol (PEG) nanoshell with a sharp gel-liquid phase transition for rapid drug release at hyperthermia temperature range.
A new mechanism of thermal sensitivity for rapid drug release and low systemic toxicity in hyperthermia and thermal ablation temperature ranges

Dabbagh A, Abdullah BJ, Abu Kasim NH, Abdullah H, Hamdi M

Int J Hyperthermia, 2015 Jun;31(4):375-85.
PMID: 25716769 DOI: 10.3109/02656736.2015.1006268

The aim of this paper was to introduce a new mechanism of thermal sensitivity in nanocarriers that results in a relatively low drug release at physiological temperature and rapid release of the encapsulated drug at hyperthermia and thermal ablation temperature range (40-60 °C).
Reusable heat-sensitive phantom for precise estimation of thermal profile in hyperthermia application

Dabbagh A, Abdullah BJ, Abu Kasim NH, Ramasindarum C

Int J Hyperthermia, 2014 Feb;30(1):66-74.
PMID: 24286257 DOI: 10.3109/02656736.2013.854930

The emergence of thermal modalities has promoted the use of heat-sensitive phantoms for calibration, measurement, and verification purposes. However, development of durable phantoms with high precision ability to represent the temperature distribution remains a challenge. This study aims to introduce a reusable phantom that provides an accurate assessment of the heated region in various thermal modalities.
Influence of natural convection on gold nanorods-assisted photothermal treatment of bladder cancer in mice

Ooi EH, Popov V, Alfano M, Cheong JKK

Int J Hyperthermia, 2020;37(1):634-650.
PMID: 32538190 DOI: 10.1080/02656736.2020.1771437

Background: The thermally-induced urine flow can generate cooling that may alter the treatment outcome during hyperthermic treatments of bladder cancer. This paper investigates the effects of natural convection inside the bladder and at skin surface during gold nanorods (GNR) - assisted photothermal therapy (PTT) of bladder cancer in mice. Methods: 3D models of mouse bladder at orientations corresponding to the mouse positioned on its back, its side and its abdomen were examined. Numerical simulations were carried out for GNR volume fractions of 0.001, 0.005 and 0.01% and laser power of 0.2 and 0.3 W. Results: The obtained results showed that cooling due to natural convection inside the bladder and above the skin depends on the mouse orientation. For a mouse positioned on its back, on its side or on its abdomen, the maximum temperature achieved inside the tumour at 0.001% GNR volume fraction and 0.2 W laser power was 55.2°C, 50.0°C and 52.2°C, respectively compared to 56.8°C when natural convection was not considered. The average thermal gradients when natural convection was considered were also lower, suggesting a more homogenous temperature distribution. Conclusions: Natural convection inside the bladder can be beneficial but also detrimental to GNR-assisted PTT depending on the level of heating. At low levels of heating due to low GNR volume fraction and/or laser power, flow inside the bladder may dissipate heat from the targeted tissue; making the treatment ineffective. At high levels of heating due to high GNR volume fraction and/or laser power, cooling may prevent excessive thermal damage to surrounding tissues.
Magnetic resonance imaging features influencing high-intensity focused ultrasound ablation of adenomyosis with a nonperfused volume ratio of ≥90% as a measure of clinical treatment success: retrospective multivariate analysis

Keserci B, Duc NM

Int J Hyperthermia, 2018;35(1):626-636.
PMID: 30307340 DOI: 10.1080/02656736.2018.1516301

OBJECTIVE: This retrospective study aimed (1) to investigate the magnetic resonance imaging (MRI) features influencing a nonperfused volume ratio (NPVr) ≥ 90% after high-intensity focussed ultrasound (HIFU) ablation of adenomyosis, and (2) to assess the safety, which was defined in terms of adverse events (AEs) and changes in anti-Mullerian hormone (AMH) concentrations, and clinical efficacy, which was defined in terms of adenomyosis volume reduction and symptom improvement at 6 months' follow-up.
METHODS: Sixty-six women who underwent HIFU treatment were divided into groups A (NPVr ≥90%; n = 26) and B (NPVr <90%, n = 40). Multivariate logistic regression analyses of MRI features were conducted to identify the potential predictors of an NPVr ≥90%.
RESULTS: Generalized estimating equation (GEE) analysis was used to model the prediction of an NPVr ≥90% with four significant predictors from multivariate analyses: the thickness of the subcutaneous fat layer, adenomyosis volume, T2 signal intensity (SI) ratio of adenomyosis to myometrium, and the Ktrans ratio of adenomyosis to myometrium. Clinical efficacy was significantly greater in group A than in group B. The findings showed no serious AEs and no significant differences between AMH concentrations before and 6 months after treatment.
CONCLUSIONS: The present retrospective study demonstrated that achievement of NPVr ≥90% as a measure of clinical treatment success in MRI-guided HIFU treatment of adenomyosis using multivariate analyses and a prediction model is clinically possible without compromising the safety of patients.
Polyethylene glycol-coated porous magnetic nanoparticles for targeted delivery of chemotherapeutics under magnetic hyperthermia condition

Dabbagh A, Hedayatnasab Z, Karimian H, Sarraf M, Yeong CH, Madaah Hosseini HR, et al.

Int J Hyperthermia, 2019;36(1):104-114.
PMID: 30428737 DOI: 10.1080/02656736.2018.1536809

PURPOSE: Although magnetite nanoparticles (MNPs) are promising agents for hyperthermia therapy, insufficient drug encapsulation efficacies inhibit their application as nanocarriers in the targeted drug delivery systems. In this study, porous magnetite nanoparticles (PMNPs) were synthesized and coated with a thermosensitive polymeric shell to obtain a synergistic effect of hyperthermia and chemotherapy.
MATERIALS AND METHODS: PMNPs were produced using cetyltrimethyl ammonium bromide template and then coated by a polyethylene glycol layer with molecular weight of 1500 Da (PEG1500) and phase transition temperature of 48 ± 2 °C to endow a thermosensitive behavior. The profile of drug release from the nanostructure was studied at various hyperthermia conditions generated by waterbath, magnetic resonance-guided focused ultrasound (MRgFUS), and alternating magnetic field (AMF). The in vitro cytotoxicity and hyperthermia efficacy of the doxorubicin-loaded nanoparticles (DOX-PEG1500-PMNPs) were assessed using human lung adenocarcinoma (A549) cells.
RESULTS: Heat treatment of DOX-PEG1500-PMNPs containing 235 ± 26 mg·g-1 DOX at 48 °C by waterbath, MRgFUS, and AMF, respectively led to 71 ± 4%, 48 ± 3%, and 74 ± 5% drug release. Hyperthermia treatment of the A549 cells using DOX-PEG1500-PMNPs led to 77% decrease in the cell viability due to the synergistic effects of magnetic hyperthermia and chemotherapy.
CONCLUSION: The large pores generated in the PMNPs structure could provide a sufficient space for encapsulation of the chemotherapeutics as well as fast drug encapsulation and release kinetics, which together with thermosensitive characteristics of the PEG1500 shell, make DOX-PEG1500-PMNPs promising adjuvants to the magnetic hyperthermia modality.
Experimental assessment on feasibility of computed tomography-based thermometry for radiofrequency ablation on tissue equivalent polyacrylamide phantom

Tan D, Mohamad NA, Wong YH, Yeong CH, Cheah PL, Sulaiman N, et al.

Int J Hyperthermia, 2019;36(1):554-561.
PMID: 31132888 DOI: 10.1080/02656736.2019.1610800

Purpose: This study aimed to evaluate the effects of various computed tomography (CT) acquisition parameters and metal artifacts on CT number measurement for CT thermometry during CT-guided thermal ablation. Methods: The effects of tube voltage (100-140 kVp), tube current (20-250 mAs), pitch (0.6-1.5) and gantry rotation time (0.5, 1.0 s) as well as metal artifacts from a radiofrequency ablation (RFA) needle on CT number were evaluated using liver tissue equivalent polyacrylamide (PAA) phantom. The correlation between CT number and temperature from 37 to 80 °C was studied on PAA phantom using optimum CT acquisition parameters. Results: No statistical significant difference (p > 0.05) was found on CT numbers under the variation of different acquisition parameters for the same temperature setting. On the other hand, the RFA needle has induced metal artifacts on the CT images of up to 8 mm. The CT numbers decreased linearly when the phantom temperature increased from 37 to 80 °C. A linear regression analysis on the CT numbers and temperature suggested that the CT thermal sensitivity was -0.521 ± 0.061 HU/°C (R2 = 0.998). Conclusion: CT thermometry is feasible for temperature assessment during RFA with the current CT technology, which produced a high CT number reproducibility and stable measurement at different CT acquisition parameters. Despite being affected by metal artifacts, the CT-based thermometry could be further developed as a tissue temperature monitoring tool during CT-guided thermal ablation.
Comparison between single- and dual-porosity models for fluid transport in predicting lesion volume following saline-infused radiofrequency ablation

Ooi EH, J Y Chia N, Ooi ET, Foo JJ, Liao IY, R Nair S, et al.

Int J Hyperthermia, 2018 12;34(8):1142-1156.
PMID: 29490513 DOI: 10.1080/02656736.2018.1437282

A recent study by Ooi and Ooi (EH Ooi, ET Ooi, Mass transport in biological tissues: Comparisons between single- and dual-porosity models in the context of saline-infused radiofrequency ablation, Applied Mathematical Modelling, 2017, 41, 271-284) has shown that single-porosity (SP) models for describing fluid transport in biological tissues significantly underestimate the fluid penetration depth when compared to dual-porosity (DP) models. This has raised some concerns on whether the SP model, when coupled with models of radiofrequency ablation (RFA) to simulate saline-infused RFA, could lead to an underestimation of the coagulation size. This paper compares the coagulation volumes obtained following saline-infused RFA predicted based on the SP and DP models for fluid transport. Results showed that the SP model predicted coagulation zones that are consistently 0.5 to 0.9 times smaller than that of DP model. This may be explained by the low permeability value of the tissue interstitial space, which causes the majority of the saline to flow through the vasculature. The absence of fluid flow tracking in the vasculature in the SP model meant that any flow of saline into the vasculature is treated as losses and do not contribute to the saline penetration depth of the tissue. Comparisons with experimental results from the literature revealed that the DP models predicted coagulation zone sizes that are closer to the experimental values than the SP models. This supports the hypothesis that the SP model is a poor choice for simulating the outcome of saline-infused RFA.