Ultrasound‐mediated nano‐sized drug delivery systems for cancer treatment: Multi‐scale and multi‐physics computational modeling

Abstract

Computational modeling enables researchers to study and understand various complex biological phenomena in anticancer drug delivery systems (DDSs), especially nano‐sized DDSs (NSDDSs). The combination of NSDDSs and therapeutic ultrasound (TUS), that is, focused ultrasound and low‐intensity pulsed ultrasound, has made significant progress in recent years, opening many opportunities for cancer treatment. Multiple parameters require tuning and optimization to develop effective DDSs, such as NSDDSs, in which mathematical modeling can prove advantageous. In silico computational modeling of ultrasound‐responsive DDS typically involves a complex framework of acoustic interactions, heat transfer, drug release from nanoparticles, fluid flow, mass transport, and pharmacodynamic governing equations. Owing to the rapid development of computational tools, modeling the different phenomena in multi‐scale complex problems involved in drug delivery to tumors has become possible. In the present study, we present an in‐depth review of recent advances in the mathematical modeling of TUS‐mediated DDSs for cancer treatment. A detailed discussion is also provided on applying these computational models to improve the clinical translation for applications in cancer treatment.This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

Integrating Therapeutic Ultrasound With Nanosized Drug Delivery Systems in the Battle Against Cancer

“…Furthermore, careful evaluation of the drug release kinetics from carriers in various NSDDSs, the duration of ultrasound exposure in different tumor environments (extracellular, intravascular, and intracellular), and the mode of nanoparticle administration (eg, intravenous, intratumoral, and intraperitoneal) is essential to ascertain the risk-to-benefit ratio effectively. 4,20…”

“…Sophisticated spatial–temporal multiscale and multiphysics computational models can be employed to explore the challenges in delivering anti-cancer agents within the complex and heterogeneous tumor microenvironment. 20,22…”

“…The multiscale and multiphysics modeling of TUS-triggered NSDDSs encompasses multiple stages and principles, including the characterization of the acoustic wave field, drug release from nanoparticles through either thermal or nonthermal responses induced by TUS, interstitial fluid flow, drug transport within various spaces, and drug delivery to cells using pharmacodynamics models. 20,22 The Pennes bioheat transfer equation can be used to model the temperature distribution within the target area to simulate drug release from nanoparticles when TUS-induced heat is significant. Conversely, if nonthermal effects of TUS drive drug release, the model integrates acoustic streaming, acoustic radiation force, and cavitation, with drug release correlated to the acoustic pressure/intensity profile.…”

“…Conversely, if nonthermal effects of TUS drive drug release, the model integrates acoustic streaming, acoustic radiation force, and cavitation, with drug release correlated to the acoustic pressure/intensity profile. 20 On the other hand, machine learning algorithms may play a pivotal role in analyzing intricate datasets and identifying patterns to improve predictions and optimize various parameters. This approach contributes to the development of personalized treatment strategies by leveraging patient-specific data.…”

“…Both preclinical (in silico, ex vivo, in vitro, and in vivo) and human clinical trials on various cancer cell lines and tumor types are conducted in many research labs and medical hospitals to understand the effect of TUS-activated NSDDSs. In recent studies, in silico approaches have been investigated in TUS (mostly focused ultrasound [FUS])-activated NSDDSs, 14,20–22 while ex vivo trials for unfocused TUS (ie, LIPUS)-triggered drug release from gold nanoparticles have also been investigated. 13,14 Multiple cell lines, involving leukemia, breast cancer, colon adenocarcinoma, ovarian carcinoma, and colorectal carcinoma have also been studied in in vitro preclinical experiments.…”