RT Journal Article
SR Electronic
T1 Drug-loaded nanoparticles for cancer therapy: a high-throughput multicellular agent-based modeling study
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2024.04.09.588498
DO 10.1101/2024.04.09.588498
A1 Wang, Yafei
A1 Bucher, Elmar
A1 Rocha, Heber
A1 Jadhao, Vikram
A1 Metzcar, John
A1 Heiland, Randy
A1 Frieboes, Hermann B.
A1 Macklin, Paul
YR 2024
UL http://biorxiv.org/content/early/2024/07/25/2024.04.09.588498.abstract
AB Interactions between biological systems and engineered nanomaterials have become an important area of study due to the application of nanomaterials in medicine. In particular, the application of nanomaterials for cancer diagnosis or treatment presents a challenging opportunity due to the complex biology of this disease spanning multiple time and spatial scales. A system-level analysis would benefit from mathematical modeling and computational simulation to explore the interactions between anticancer drug-loaded nanoparticles (NPs), cells, and tissues, and the associated parameters driving this system and a patient’s overall response. Although a number of models have explored these interactions in the past, few have focused on simulating individual cell-NP interactions. This study develops a multicellular agent-based model of cancer nanotherapy that simulates NP internalization, drug release within the cell cytoplasm, “inheritance” of NPs by daughter cells at cell division, cell pharmacodynamic response to the intracellular drug, and overall drug effect on tumor dynamics. A large-scale parallel computational framework is used to investigate the impact of pharmacokinetic design parameters (NP internalization rate, NP decay rate, anticancer drug release rate) and therapeutic strategies (NP doses and injection frequency) on the tumor dynamics. In particular, through the exploration of NP “inheritance” at cell division, the results indicate that cancer treatment may be improved when NPs are inherited at cell division for cytotoxic chemotherapy. Moreover, smaller dosage of cytostatic chemotherapy may also improve inhibition of tumor growth when cell division is not completely inhibited.This work suggests that slow delivery by “heritable” NPs can drive new dimensions of nanotherapy design for more sustained therapeutic response.Competing Interest StatementThe authors have declared no competing interest.