Preclinical Studies in Small Animals for Advanced Drug Delivery Using Hyperthermia and Intravital Microscopy

Priester, Marjolein I; Curto, Sergio; Seynhaeve, Ann L.B.; Perdomo, Anderson Cruz; Amin, Mohamadreza; Agnass, Pierre; Salimibani, Milad; Faridi, Pegah; Prakash, Punit; Rhoon, Gerard C. van; Hagen, Timo L.M. ten

doi:10.3390/cancers13205146

Cited by 7 publications

(3 citation statements)

References 40 publications

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“…To achieve these objectives, we investigated the ability to apply the focused RF-induced heating of 3D cell spheroid cell cultures. To the best of our knowledge, this is the first attempt to develop such an experimental setup, although similar efforts for in vivo experiments have been reported and have the potential to be adapted for in vitro experiments [35]. Similarly to the current effort, a focused US applicator has recently been developed and has the ability to be used for similar heating targets [36].…”

Section: Discussionmentioning

confidence: 88%

Design and Validation of Experimental Setup for Cell Spheroid Radiofrequency-Induced Heating

Androulakis

Ferrero

Oossanen

et al. 2023

Sensors

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While hyperthermia has been shown to induce a variety of cytotoxic and sensitizing effects on cancer tissues, the thermal dose–effect relationship is still not well quantified, and it is still unclear how it can be optimally combined with other treatment modalities. Additionally, it is speculated that different methods of applying hyperthermia, such as water bath heating or electromagnetic energy, may have an effect on the resulting biological mechanisms involved in cell death or in sensitizing tumor cells to other oncological treatments. In order to further quantify and characterize hyperthermia treatments on a cellular level, in vitro experiments shifted towards the use of 3D cell spheroids. These are in fact considered a more representative model of the cell environment when compared to 2D cell cultures. In order to perform radiofrequency (RF)-induced heating in vitro, we have recently developed a dedicated electromagnetic field applicator. In this study, using this applicator, we designed and validated an experimental setup which can heat 3D cell spheroids in a conical polypropylene vial, thus providing a reliable instrument for investigating hyperthermia effects at the cellular scale.

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Section: Discussionmentioning

confidence: 88%

Design and Validation of Experimental Setup for Cell Spheroid Radiofrequency-Induced Heating

Androulakis

Ferrero

Oossanen

et al. 2023

Sensors

Self Cite

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“…More importantly, this animal setting has provided invaluable insights for improving drug delivery and testing new systems. For instances, to apply heat locally in the dorsal skinfold chamber, an external circular electric heating coil was constructed, to fit into our chamber holder [ 58 ]. Several heating schedules (i.e., before, during, or before and after injection of liposomes) have been investigated, and via intravital microscopy, the drug release and uptake kinetics was evaluated.…”

Section: Visualizing the Intratumoral Fate Of Nanomedicines By Intrav...mentioning

confidence: 99%

Liposomal Drug Delivery Systems for Cancer Therapy: The Rotterdam Experience

et al. 2022

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At the Nanomedicine Innovation Center (NICE) at the Erasmus MC in Rotterdam, we have approached the treatment of cancer by starting with a vision of first establishing a platform that enables us to overcome the low levels of drugs delivered to tumors and the issue of dose-limiting toxicity. Showing that a reduction of the volume of distribution, and a lowering of toxicity and side-effects, accompanied by augmented intratumoral drug delivery, could change outcomes in patients, paved the way to target, not only localized disease, but also systemic and metastasized cancers. In particular, the detailed studies with intravital microscopy we performed at NICE provided us with the necessary insights and affected to a large extent our program on liposome-based cancer therapy. Together with our experience with the loco-regional treatment of cancer, this helped us to develop a program that focused on the subsequent aspects discussed here. We recognized that passive accumulation of nanoparticles was not as effective as previously believed and undertook to improve the local accumulation by changing the tumor pathophysiology and, in particular, the vascular permeability. We added the targeting of liposomes using vascular and tumor directed moieties, to improve cellular drug delivery. To improve payload delivery, we studied the modification of liposomes with phospholipids that help passive drug release and augment cellular accumulation. Second, and importantly, modification of liposomes was undertaken, to enable triggered drug release. The capability for modifying liposomes to respond to a trigger, and the ability to now apply an external trigger (e.g., hyperthermia) and specifically reach the tumor volume, resulted in the current smart drug delivery systems. Our experience at NICE, after a few decades of research on lipid-based nanoparticles, shows that, after the first liposomal formulation registered for clinical application in cancer therapy, further developments quickly followed, while further clinical applications lagged behind. Now we need to focus on and make the next steps towards the clinic, to fulfil the promise that is found there.

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“…Beyond cancer therapy, MDs offer additional advantages, including increased biocompatibility, low toxicity, and utility in both the diagnosis and treatment of diseases Mody et al (2014); Mohammadi, Raői-Tabar, and Sasanpour (2022); Rudramurthy and Swamy (2018). MNPs, when combined with microdevices can serve as, among others, effective heat mediators for hyperthermia treatment or enable the targeted administration of drugs, contributing to a more controlled and regulated drug dosage Camargo, Pacheco, and Rodriguez (2021); Chandrasekharan et al (2020); Christfort et al (2022); Gholami et al (2020); Priester et al (2021); Wang, Li, and Nie (2021).…”

Section: Introductionmentioning

confidence: 99%

Modeling the Elastic Collision of Nanoparticle with Erytrocite: Viscoelastic Effects on Angular Dispersion

Rivera,

Barrantes,

Rodriguez

2024

Preprint

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To achieve effective drug administration and minimize toxicity, it is crucial to predict the movement and trajectory of nanoparticles, or other nanodevices, when they interact with blood components. In this study, a dispersion model was developed for the interaction between a nanoparticle (NP) and a red blood cell (RBC) considering an elastic collision, assuming that RBCs are the main scattering center in drug delivery through the bloodstream. To analyze the model, the viscoelastic characteristics of the RBC membrane were highlighted, which allowed for the study of interaction in the collision interval through classical molecular dynamics. The kinetic and energetic behavior of the interaction was described, taking into account the drag force exerted by the RBC surface on the nanoparticle and the viscoelastic force that causes a non-linear displacement of the nanoparticle. Additionally, an analytical model based on the trajectory vectors before and after collision, associated with the position and velocity vectors of the nanoparticle, was proposed. This allowed for obtaining the angular dispersion profiles and quantifying the differential effective collision section between the particle and the RBC. The results showed that dispersion depends on the biconcave and symmetrical geometry of the RBC, as well as the velocity and direction of the nanoparticle movement.

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Preclinical Studies in Small Animals for Advanced Drug Delivery Using Hyperthermia and Intravital Microscopy

Cited by 7 publications

References 40 publications

Design and Validation of Experimental Setup for Cell Spheroid Radiofrequency-Induced Heating

Design and Validation of Experimental Setup for Cell Spheroid Radiofrequency-Induced Heating

Liposomal Drug Delivery Systems for Cancer Therapy: The Rotterdam Experience

Modeling the Elastic Collision of Nanoparticle with Erytrocite: Viscoelastic Effects on Angular Dispersion

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