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Updated: Nov 1, 2025
Author Spotlight: Computing the Effects of a Local Radiofrequency Hyperthermia Intervention on Tumor Biomechanics
Published on: December 1, 2023
Computational model of silica nanoparticle penetration into tumor spheroids: Effects of methoxy and carboxy PEG
Abhignyan Nagesetti1, George S Dulikravich2, Helcio R B Orlande3
1Department of Biomedical Engineering, Florida International University, Miami, Florida, USA.
Abstract:
Drug delivery to tumors suffers from poor solubility, specificity, diffusion through the tumor micro-environment and nonoptimal interactions with components of the extracellular matrix and cell surface receptors. Nanoparticles and drug-polymer complexes address many of these problems. However, large size exasperates the problem of slow diffusion through the tumor. Three-dimensional tumor spheroids are good models to evaluate approaches to mitigate these difficulties and aid in design strategies to improve the delivery of drugs to treat cancer effectively. Diffusion of drug carriers is highly dependent on cell uptake rate parameters (association/dissociation) and temperature. Hyperthermia increases molecular transport and is known to act synergistically with chemotherapy to improve treatment. This study presents a new inverse estimation approach based on Bayesian probability for estimating nanoparticle cell uptake rates from experiments. The parameters were combined with a finite element computational model of nanoparticle transport under hyperthermia conditions to explore its effect on tumor porosity, diffusion and particle binding (association and dissociation) at cell surfaces. Carboxy-PEG-silane (cPEGSi) nanoparticles showed higher cell uptake compared to methoxy-PEG-silane (mPEGSi) nanoparticles. Simulations were consistent with experimental results from Skov-3 ovarian cancer spheroids. Amorphous silica (cPEGSi) nanoparticles (58 nm) concentrated at the periphery of the tumor spheroids at 37°C but mild hyperthermia (43°C) increased nanoparticle penetration. Thus, hyperthermia may enhance cancer treatment by improving blood delivery to tumors, enhancing extravasation and penetration into tumors, trigger release of drug from the carrier at the tumor site and possibly lead to synergistic anti-cancer activity with the drug.
Insights
Hyperthermia enhances nanoparticle drug delivery into tumors by improving penetration and uptake. This study developed a Bayesian method to estimate nanoparticle cell uptake rates, showing mild heat significantly increases drug carrier diffusion in ovarian cancer spheroids.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Tumor drug delivery faces challenges like poor solubility, specificity, and diffusion.
- Nanoparticles offer solutions but their size can hinder tumor penetration.
- Hyperthermia (elevated temperature) can synergize with chemotherapy and improve drug transport.
Purpose of the Study:
- To develop a Bayesian inverse estimation method for nanoparticle cell uptake rates.
- To computationally model nanoparticle transport in tumors under hyperthermia.
- To investigate the impact of hyperthermia on tumor porosity, diffusion, and particle binding.
Main Methods:
- Bayesian probability-based inverse estimation for nanoparticle cell uptake.
- Finite element computational modeling of nanoparticle transport.
- Experimental validation using 3D tumor spheroids (Skov-3 ovarian cancer cells).
Main Results:
- Carboxy-PEG-silane (cPEGSi) nanoparticles exhibited higher cell uptake than methoxy-PEG-silane (mPEGSi) nanoparticles.
- Mild hyperthermia (43°C) significantly increased the penetration of amorphous silica (cPEGSi) nanoparticles into tumor spheroids.
- Simulations correlated well with experimental findings on nanoparticle behavior.
Conclusions:
- Hyperthermia can enhance nanoparticle-based cancer drug delivery by improving tumor penetration.
- The developed Bayesian method aids in understanding and optimizing nanoparticle-tumor interactions.
- Mild hyperthermia presents a promising strategy to improve the efficacy of nanoparticle drug delivery systems in cancer treatment.
