Computational Modeling of Combination of Magnetic Hyperthermia and Temperature-Sensitive Liposome for Controlled Drug Release in Solid Tumor

Abstract

Combination therapy, a treatment modality that combines two or more therapeutic methods, provides a novel pathway for cancer treatment, as it targets the region of interest (ROI) in a characteristically synergistic or additive manner. To date, liposomes are the only nano-drug delivery platforms that have been used in clinical trials. Here, we speculated that it could be promising to improve treatment efficacy and reduce side effects by intravenous administration of thermo-sensitive liposomes loaded with doxorubicin (TSL-Dox) during magnetic hyperthermia (MHT). A multi-scale computational model using the finite element method was developed to simulate both MHT and temperature-sensitive liposome (TSL) delivery to a solid tumor to obtain spatial drug concentration maps and temperature profiles. The results showed that the killing rate of MHT alone was about 15%, which increased to 50% using the suggested combination therapy. The results also revealed that this combination treatment increased the fraction of killed cells (FKCs) inside the tumor compared to conventional chemotherapy by 15% in addition to reducing side effects. Furthermore, the impacts of vessel wall pore size, the time interval between TSL delivery and MHT, and the initial dose of TSLs were also investigated. A considerable reduction in drug accumulation was observed in the tumor by decreasing the vessel wall pore size of the tumor. The results also revealed that the treatment procedure plays an essential role in the therapeutic potential of anti-cancer drugs. The results suggest that the administration of MHT can be beneficial in the TSL delivery system and that it can be employed as a guideline for upcoming preclinical studies.

Ultrasound‐mediated nano‐sized drug delivery systems for cancer treatment: Multi‐scale and multi‐physics computational modeling

“…The stimuli‐responsive drug release approach has many variables that are spatially‐temporally varying and interdependent (Dewhirst & Secomb, 2017; Tehrani et al, 2021; Ten Hagen et al, 2021; Figure 2c). Transport characteristics (e.g., plasma half‐life and microvessel permeability) depend on whether the drug is free or associated with a DDS.…”

“…Drugs may diffuse back into the bloodstream, due to the concentration gradient across the vessel wall. (c) Schematic depicting the interaction among three categories: physiology/biology, DDS, and drug (extracted with modifications from Ten Hagen et al, 2021).…”

“…This limitation of conventional NP-based DDSs has inspired researchers to look for various ways to enhance the drug delivery efficacy of NPs. Since the EPR has been shown to be less prominent in human tumors, alternate approaches are required to increase drug bioavailability locally (Danhier, 2016;Ten Hagen et al, 2021). Active targeting using stimuli-triggered drug release from nanocarriers could be advantageous.…”

The future opportunities and remaining challenges in the application of nanoparticle‐mediated hyperthermia combined with chemo‐radiotherapy in cancer

“…Generally, liposomes are small vesicles made up of a phospholipid bilayer membrane (Bangham, 1993). Tehrani et al demonstrated that thermo‐sensitive liposomes loaded with doxorubicin (TSL‐Dox) with magnetic hyperthermia (MHT) resulted in more effective treatment, as well as Rahim et al's study shows their fabricated liposomes give sufficient insight into a safe and effective chemotherapy‐based therapeutic method for hepatocellular cancer (Rahim et al, 2021; Tehrani et al, 2022). Also, Bredlau et al showed that TSL‐Dox with localized hyperthermia could enhance localized doxorubicin delivery to the brain while causing no substantial neurological deficits (Bredlau et al, 2018).…”

Advances in biomaterials for the treatment of retinoblastoma

“…[299][300][301] Therapeutic breakthroughs of liposomal tools also include their aptitude to be chemically and physically modulated, 302 their potency to encapsulate different agents including chemotherapeutics and genetic molecules, 303,304 their enhanced capability to reach the tumor site via different administration procedures, 305 and their ability to persuade a tuned release of the loaded agents. [306][307][308] All of these aspects have made liposome nanosystems an increasingly attractive drug delivery system. Recent signs of progress in the research sector of liposomal technology have led to innovative claims in the diagnosis and theranostics of retinoblastoma.…”