TY - JOUR
T1 - From Blood Flow to Tumor Cell Internalization
T2 - A Multistage Computational Model of Nanoparticle Dynamics
AU - González-Garcinuño, Álvaro
AU - Martin del Valle, Eva
AU - Kenjeres, Sasa
PY - 2026
Y1 - 2026
N2 - Background: Understanding the transport of nanoparticles within blood vessels and their distribution in tumor tissues is crucial for the successful implementation of nanotechnological strategies in clinical practice. Although numerous studies have examined nanoparticle transport in blood flow, none have comprehensively investigated all the sequential steps a nanoparticle must undergo prior to internalization by target cells. Methods: A computational framework was developed in COMSOL Multiphysics to simulate nanoparticle (NP) transport from systemic administration through to tumor cell internalization. The model integrates three coupled stages: (1) NP movement within a non-Newtonian blood flow; (2) trans-endothelial transport; and (3) NP motion within the tumor stroma, incorporating affinity forces to capture ligand–receptor interactions. The tumor geometry was reconstructed, including cancer cells and fibroblasts, to reproduce physiological porosity. Multiple case studies were conducted to evaluate the impact of particle density, injection velocity, and size on NP biodistribution. Results: The computational model effectively simulates nanoparticle transport across all stages. Notably, it is the first model in the literature to incorporate the affinity of functionalized nanoparticles, which facilitates ligand–receptor interactions for targeted delivery. Simulation outcomes indicate that a low Stokes number is critical for ensuring a higher percentage of particles reach the end of the capillary network. Furthermore, surface modification of nanoparticles with ligands promotes more specific distribution within the stroma, reducing the percentage of nanoparticles that fail to reach target cells by approximately 50% Conclusions: A novel and comprehensive computational model has been developed to include the entire process of nanoparticle distribution following systemic administration, including specific recognition by cellular receptors.
AB - Background: Understanding the transport of nanoparticles within blood vessels and their distribution in tumor tissues is crucial for the successful implementation of nanotechnological strategies in clinical practice. Although numerous studies have examined nanoparticle transport in blood flow, none have comprehensively investigated all the sequential steps a nanoparticle must undergo prior to internalization by target cells. Methods: A computational framework was developed in COMSOL Multiphysics to simulate nanoparticle (NP) transport from systemic administration through to tumor cell internalization. The model integrates three coupled stages: (1) NP movement within a non-Newtonian blood flow; (2) trans-endothelial transport; and (3) NP motion within the tumor stroma, incorporating affinity forces to capture ligand–receptor interactions. The tumor geometry was reconstructed, including cancer cells and fibroblasts, to reproduce physiological porosity. Multiple case studies were conducted to evaluate the impact of particle density, injection velocity, and size on NP biodistribution. Results: The computational model effectively simulates nanoparticle transport across all stages. Notably, it is the first model in the literature to incorporate the affinity of functionalized nanoparticles, which facilitates ligand–receptor interactions for targeted delivery. Simulation outcomes indicate that a low Stokes number is critical for ensuring a higher percentage of particles reach the end of the capillary network. Furthermore, surface modification of nanoparticles with ligands promotes more specific distribution within the stroma, reducing the percentage of nanoparticles that fail to reach target cells by approximately 50% Conclusions: A novel and comprehensive computational model has been developed to include the entire process of nanoparticle distribution following systemic administration, including specific recognition by cellular receptors.
KW - affinity
KW - CFD
KW - nanoparticles tracking
KW - transport modelling
KW - tumour environment
UR - http://www.scopus.com/inward/record.url?scp=105027660204&partnerID=8YFLogxK
U2 - 10.1007/s11095-026-04018-2
DO - 10.1007/s11095-026-04018-2
M3 - Article
AN - SCOPUS:105027660204
SN - 0724-8741
JO - Pharmaceutical Research
JF - Pharmaceutical Research
ER -
