Development of a Physiologically-Based Mathematical Model for Quantifying Nanoparticle Distribution in Tumors

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Mathematical Modeling

Background:

• Nanomedicine offers potential for targeted cancer drug delivery.
• Clinical translation of nanomedicine is hindered by incomplete understanding of nanoparticle behavior influenced by physiochemical and physiological factors.

Purpose of the Study:

• To develop and validate a multiscale mathematical model for assessing nanoparticle delivery efficacy in solid tumors.
• To investigate the spatiotemporal distribution of nanoparticles within pancreatic ductal adenocarcinoma (PDAC).

Main Methods:

• Integration of systemic nanoparticle disposition kinetics with NP-cell interactions within a 2D model of PDAC.
• Parameterization of the model using human physiological data from published literature.
• Verification of the multiscale approach by comparing whole-body and tissue-scale model predictions.

Main Results:

• The multiscale model accurately predicted nanoparticle concentration kinetics across different compartments.
• A higher concentration of nanoparticles was observed in the well-perfused outer tumor region compared to the necrotic inner domain.
• Model analysis confirmed the agreement between whole-body and tissue-scale predictions.

Conclusions:

• The multiscale mathematical model provides a robust framework for evaluating nanoparticle delivery to solid tumors.
• The findings highlight the importance of tumor perfusion in nanoparticle distribution.
• Further model development could optimize nanoparticle design and inform clinical interventions for cancer therapy.