Organ-on-chip systems as a model for nanomedicine

Abstract

Nanomedicine is giving rise to increasing numbers of successful drugs, including cancer treatments, molecular imaging agents, and novel vaccine formulations. However, traditionally available model systems offer limited clinical translation and, compared to the number of preclinical studies, the approval rate of nanoparticles (NPs) for clinical use remains disappointingly low. A new paradigm of modeling biological systems on microfluidic chips has emerged in the last decade and is being gradually adopted by the nanomedicine community. These systems mimic tissues, organs, and diseases like cancer, on devices with small physical footprints and complex geometries. In this review, we report studies that used organ-on-chip approaches to study the interactions of NPs with biological systems. We present examples of NP toxicity studies, studies using biological NPs such as viruses, as well as modeling biological barriers and cancer on chip. Organ-on-chip systems present an exciting opportunity and can provide a renewed direction for the nanomedicine community.

Figure 1.. Organ-on-Chip offer features with sizes from the sub-micron to the millimetre scale.

OoCs recapitulate the multiscale structure of biological organisms: channels and chambers are comparable to blood vessels and the tissue microenvironment, while their interconnects (e.g., a porous membrane) allow for controlled transport of smaller species, such as small molecules, proteins, and nanoparticles. The exact dimensions of each of these components can be fine-tuned for the specific application, allowing exquisite control over the model system, on the length scales important to biological processes.

Figure 2.. Toxicity on chip.

(A) Exposure of neuron-like PC-12 cells to different surface-modified quantum dots (QDs) lead to morphological alterations and cytotoxicity. The neuron-on-chip allows selective exposure of the QDs to the axon or the soma. (B) Nanoparticles induce apoptosis in PC12 cells, HPAEpiC, and HUVEC in a lung-on-chip nanotoxicity assay.^,

Figure 3.. NP transport across a placental barrier on a chip.

(A) Dynamic conditions lead to the formation of microvilli in BeWo cells. BeWo cells and HUVECs formed uniform continuous layer. Cell morphology was characterized by staining F-actin (Alexa-Fluor-488-phalloidin) and cell nuclei (DAPI). (B) Exposure of cells to a high concentration of TiO2-NPs lead to ROS generation.

Figure 4.. BBB permeation model.

AP2 decorated NPs loaded with CDDP were used to assess BBB permeation in an on-chip GMB model. The NPs showed higher treatment efficacy compared to bare CDDP NPs and free CDDP.

Figure 5.. Drug-loaded macrophages home to the tumor in vivo and on-chip.

Macrophages naturally take up NPs and can serve as vehicles. ToC systems can help understand the complex interaction between immune-cells, NPs, and tumor, to achieve better targeting strategies.

Figure 6.. siRNA-loaded NPs modulate tumor angiogenesis on a chip.

(A) Multi-compartment chip as a model for angiogenesis. (B) Brightfield images show the angiogenic sprouting under the effect of different siRNA-loaded NPs compared to the control. (C,D) siVEGFR NPs in three different dosages inhibit angiogenesis.

Figure 7.. Magnetic hyperthermia therapy on-chip.

(A) Magnetic NPs under an alternating magnetic field induce hyperthermia in a GBM-on-chip model. (B) Cell death assay showed complete tumor elimination after 30 minutes of MHT.