Related Experiment Video
Updated: Jul 15, 2025
Designing Microfluidic Devices for Studying Cellular Responses Under Single or Coexisting Chemical/Electrical/Shear Stress Stimuli
Published on: August 13, 2016
Cellular Efficacy of Fattigated Nanoparticles and Real-Time ROS Occurrence Using Microfluidic Hepatocarcinoma Chip
Hoyoung Kim1, Eun-Ji Kim1, Hai V Ngo1
1College of Pharmacy, Ajou University, Suwon 16499, Republic of Korea.
Abstract:
The objective of this study was to evaluate the effectiveness of organ-on-chip system investigating simultaneous cellular efficacy and real-time reactive oxygen species (ROS) occurrence of anticancer drug-loaded nanoparticles (NPs) using hepatocarcinoma cells (HepG2) chip system under static and hepatomimicking shear stress conditions (5 dyne/cm2). Then, the role of hepatomimetic shear stress exposed to HepG2 and drug solubility were compared. The highly soluble doxorubicin (DOX) and poorly soluble paclitaxel (PTX) were chosen. Fattigated NPs (AONs) were formed via self-assembly of amphiphilic albumin (HSA)-oleic acid conjugate (AOC). Then, drug-loaded AONs (DOX-AON or PTX-AON) were exposed to a serum-free HepG2 medium at 37 °C and 5% carbon dioxide for 24 h using a real-time ROS sensor chip-based microfluidic system. The cellular efficacy and simultaneous ROS occurrence of free drugs and drug-loaded AONs were compared. The cellular efficacy of drug-loaded AONs varied in a dose-dependent manner and were consistently correlated with real-time of ROS occurrence. Drug-loaded AONs increased the intracellular fluorescence intensity and decreased the cellular efficacy compared to free drugs under dynamic conditions. The half-maximal inhibitory concentration (IC50) values of free DOX (13.4 μg/mL) and PTX (54.44 μg/mL) under static conditions decreased to 11.79 and 38.43 μg/mL, respectively, under dynamic conditions. Furthermore, DOX- and PTX-AONs showed highly decreased IC50 values of 5.613 and 21.86 μg/mL, respectively, as compared to free drugs under dynamic conditions. It was evident that cellular efficacy and real-time ROS occurrence were well-correlated and highly dependent on the drug-loaded nanostructure, drug solubility and physiological shear stress.
Insights
This study shows that drug-loaded nanoparticles (NPs) on an organ-on-chip system effectively deliver anticancer drugs, correlating cellular efficacy with real-time reactive oxygen species (ROS) occurrence under physiological shear stress.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Pharmacology
Background:
- Organ-on-chip systems offer advanced in vitro models for drug testing.
- Reactive oxygen species (ROS) play a crucial role in cancer drug efficacy.
- Physiological shear stress can significantly influence cellular responses to drugs.
Purpose of the Study:
- To evaluate anticancer drug-loaded nanoparticles (NPs) using a HepG2 organ-on-chip system.
- To investigate the simultaneous cellular efficacy and real-time ROS occurrence under static and dynamic conditions.
- To compare the effects of drug solubility and hepatomimetic shear stress on drug delivery.
Main Methods:
- Utilized a HepG2 cell chip system with a real-time ROS sensor microfluidic device.
- Formulated amphiphilic albumin-oleic acid conjugate nanoparticles (AONs) loaded with doxorubicin (DOX) and paclitaxel (PTX).
- Assessed cellular efficacy and ROS generation of free drugs versus drug-loaded AONs under static and shear stress (5 dyne/cm²) conditions.
Main Results:
- Drug-loaded AONs demonstrated dose-dependent cellular efficacy correlated with ROS occurrence.
- Under dynamic conditions, drug-loaded AONs showed increased intracellular fluorescence and reduced efficacy compared to free drugs.
- Half-maximal inhibitory concentration (IC50) values were significantly lower for drug-loaded AONs under dynamic conditions compared to free drugs.
Conclusions:
- Cellular efficacy and real-time ROS occurrence are strongly correlated and influenced by nanostructure, drug solubility, and physiological shear stress.
- Organ-on-chip systems effectively model drug responses under physiological conditions.
- Nanoparticle formulation enhances drug delivery and efficacy, modulated by shear stress.
