Improving tumor treatment through intratumoral injection of drug-loaded magnetic nanoparticles and low-intensity ultrasound.

The intratumoral injection of therapeutic agents responsive to external stimuli has gained considerable interest in treating accessible tumors due to its biocompatibility and capacity to reduce side effects. For the first time, a novel approach is explored to investigate the feasibility of utilizing low-intensity ultrasound in combination with intratumoral injection of drug-loaded magnetic nanoparticles (MNPs) to thermal necrosis and chemotherapy with the objective of maximizing tumor damage while avoiding harm to surrounding healthy tissue. In this study, a mathematical framework is proposed based on a multi-compartment model to evaluate the effects of ultrasound transducer's specifications, MNPs size and distribution, and drug release in response to the tumor microenvironment characteristics. The results indicate that while a higher injection rate may increase interstitial fluid pressure, it also simultaneously enhances the concentration of the therapeutic agent. Moreover, by increasing the power and frequency of the transducer, the acoustic pressure and intensity can be enhanced. This, in turn, increases the impact on accumulated MNPs, resulting in a rise in temperature and localized heat generation. Results have demonstrated that smaller MNPs have a lower capacity to generate heat compared to larger MNPs, primarily due to the impact of sound waves on them. It is worth noting that smaller MNPs have been observed to have enhanced diffusion, allowing them to effectively spread within the tumor. However, their smaller size also leads to rapid elimination from the extracellular space into the bloodstream. To summarize, this study demonstrated that the local injection of MNPs carrying drugs not only enables localized chemotherapy but also enhances the effectiveness of low-intensity ultrasound in inducing tissue thermal necrosis. The findings of this study can serve as a valuable and reliable resource for future research in this field and contribute to the development of personalized medicine.

Analysis of Magneto-Hyperthermia Duration in Nano-sized Drug Delivery System to Solid Tumors Using Intravascular-Triggered Thermosensitive-Liposome.

Computational models have been developed as a potential platform to identify bio-interactions that cannot be properly understood by experimental models. In the present study, a mathematical model has been employed to investigate the therapeutic response of drug-loaded thermosensitive liposome (TSL) following intravascular release paradigm. Thermal field created by an alternating magnetic field is utilized to release the drug within microvessels. Determining the time required for the application of magneto-hyperthermia is the main purpose of this study. Results show that applying a long-term continuous or pulsed hyperthermia can affect the concentration level of drugs in the extracellular space. The peak value of free and bound drug concentrations in the extracellular space is equal for all hyperthermia programs. Additionally, the concentrations of free and bound drugs are retained at a higher level in pulsed mode compared to the continuous mode (i.e., area under curve (AUC) of pulsed case is slightly higher than continuous case). However, there is no significant difference in bioavailability time. Hence, onset time of tumor growth is similar for different conditions. This study shows that the appropriate time to apply hyperthermia is post-bolus injection until reaching the peak concentration profile in extracellular space. Therefore, in clinical applications similar to the present study's circumstances, continuous hyperthermia for 30 min can be a better choice. This study can be a useful guideline for experimental studies to reduce the number of in vivo tests as well as for clinical trials to make the right decision to provide optimal medication programs.

Computational modeling of thermal combination therapies by magneto-ultrasonic heating to enhance drug delivery to solid tumors.

For the first time, inspired by magnetic resonance imaging-guidance high intensity focused ultrasound (MR-HIFU) technology, i.e., medication therapy and thermal ablation in one session, in a preclinical setting based on a developed mathematical model, the performance of doxorubicin (Dox) and its encapsulation have been investigated in this study. Five different treatment methods, that combine medication therapy with mild hyperthermia by MRI contrast ([Formula: see text]) and thermal ablation via HIFU, are investigated in detail. A comparison between classical chemotherapy and thermochemistry shows that temperature can improve the therapeutic outcome by stimulating biological properties. On the other hand, the intravascular release of ThermoDox increases the concentration of free drug by 2.6 times compared to classical chemotherapy. The transport of drug in interstitium relies mainly on the diffusion mechanism to be able to penetrate deeper and reach the cancer cells in the inner regions of the tumor. Due to the low drug penetration into the tumor center, thermal ablation has been used for necrosis of the central areas before thermochemotherapy and ThermoDox therapy. Perfusion of the region around the necrotic zone is found to be damaged, while cells in the region are alive and not affected by medication therapy; so, there is a risk of tumor recurrence. Therefore, it is recommended that ablation be performed after the medication therapy. Our model describes a comprehensive assessment of MR-HIFU technology, taking into account many effective details, which can be a reliable guide towards the optimal use of drug delivery systems.