Predicting anti-tumor efficacy of multi-functional nanomedicine on decellularized hepatocellular carcinoma-on-a-chip

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Hepatocellular Carcinoma Research

Background:

• Traditional hepatocellular carcinoma (HCC) chip models exhibit limitations in replicating in vivo tumor microenvironments, leading to inaccuracies in drug efficacy prediction and high costs.
• Developing advanced in vitro models is crucial for effective anti-tumor nanomedicine screening.

Purpose of the Study:

• To develop and validate a decellularized extracellular matrix (dECM)-based hepatocellular carcinoma-on-a-chip model for high-throughput screening of anti-tumor nanomedicine.
• To assess the efficacy of a novel smart nanomedicine (NLV/Fe+DOX) in this chip model.

Main Methods:

• Co-culturing human hepatocellular carcinoma (HepG2) and normal liver (L02) cells on a 3D dECM scaffold to simulate the in vivo tumor microenvironment.
• Developing a liposome nanovesicle encapsulating doxorubicin (DOX) and ferric oxide (Fe3O4) (NLV/Fe+DOX) for targeted therapy.
• Evaluating the selective killing of HepG2 cells and the viability of L02 cells using the developed chip model and nanomedicine.

Main Results:

• The NLV/Fe+DOX nanomedicine selectively eliminated 78.59% ± 6.78% of HepG2 cells via combined chemo-chemodynamic-photothermal therapies.
• The viability of surrounding normal L02 cells remained high (>90.0%) in the chip model.
• Drug efficacy tested on the chip model showed strong correlation with established cellular and animal experimental results.

Conclusions:

• The proposed decellularized hepatocellular carcinoma-on-a-chip model offers a cost-effective and accurate platform for anti-tumor nanomedicine screening.
• This model effectively mimics the tumor microenvironment, enhancing the predictive power for drug efficacy in HCC treatment.
• The developed smart nanomedicine demonstrates significant potential for targeted HCC therapy.