Modeling of Nanotherapy Response as a Function of the Tumor Microenvironment: Focus on Liver Metastasis.

Hermann B Frieboes,Biana Godin,Shreya Raghavan

doi:10.3389/fbioe.2020.01011

Abstract

The tumor microenvironment (TME) presents a challenging barrier for effective nanotherapy-mediated drug delivery to solid tumors. In particular for tumors less vascularized than the surrounding normal tissue, as in liver metastases, the structure of the organ itself conjures with cancer-specific behavior to impair drug transport and uptake by cancer cells. Cells and elements in the TME of hypovascularized tumors play a key role in the process of delivery and retention of anti-cancer therapeutics by nanocarriers. This brief review describes the drug transport challenges and how they are being addressed with advanced in vitro 3D tissue models as well as with in silico mathematical modeling. This modeling complements network-oriented techniques, which seek to interpret intra-cellular relevant pathways and signal transduction within cells and with their surrounding microenvironment. With a concerted effort integrating experimental observations with computational analyses spanning from the molecular- to the tissue-scale, the goal of effective nanotherapy customized to patient tumor-specific conditions may be finally realized.

Highlights

Specialty section: This article was submitted to Nanobiotechnology, a section of the journal Frontiers in Bioengineering and Biotechnology
In particular for tumors less vascularized than the surrounding normal tissue, as in liver metastases, the structure of the organ itself conjures with cancer-specific behavior to impair drug transport and uptake by cancer cells
Modeling Nanotherapy Response in Tumor Microenvironment includes several scales: (a) molecular scale, including up- and down-regulation of various proteins that can signal for tumor growth or drug-efflux mechanisms; (b) nano- to micro- scale, which incorporates gradients of cell nutrients and oxygen, growth factors, and other means of cell-tocell communication; (c) micro-scale, in which interactions between cells occur in the acellular stroma compartment of the tumor; (d) micro to macro scale, which incorporates the organ architecture, blood supply, lymphatics, and other physiological factors

Summary

Introduction

Specialty section: This article was submitted to Nanobiotechnology, a section of the journal Frontiers in Bioengineering and Biotechnology. We briefly review considerations in evaluating drug efficacy in terms of adopting the appropriate 3D in vitro/ex vivo models, and consider integrated engineering examples of therapeutic efficiency directed toward hypovascularized lesions such as liver metastases.

Results

Conclusion