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Synthesis of Aptamer-PEI-g-PEG Modified Gold Nanoparticles Loaded with Doxorubicin for Targeted Drug Delivery
Published on: June 23, 2020
An interdisciplinary computational/experimental approach to evaluate drug-loaded gold nanoparticle tumor cytotoxicity
Louis T Curtis1, Christopher G England2, Min Wu3
1Department of Bioengineering, University of Louisville, KY, USA.
Aim:
Clinical translation of cancer nanotherapy has largely failed due to the infeasibility of optimizing the complex interaction of nano/drug/tumor/patient parameters. We develop an interdisciplinary approach modeling diffusive transport of drug-loaded gold nanoparticles in heterogeneously-vascularized tumors.
Materials & Methods:
Evaluated lung cancer cytotoxicity to paclitaxel/cisplatin using novel two-layer (hexadecanethiol/phosphatidylcholine) and three-layer (with high-density-lipoprotein) nanoparticles. Computer simulations calibrated to in-vitro data simulated nanotherapy of heterogeneously-vascularized tumors.
Results:
Evaluation of free-drug cytotoxicity between monolayer/spheroid cultures demonstrates a substantial differential, with increased resistance conferred by diffusive transport. Nanoparticles had significantly higher efficacy than free-drug. Simulations of nanotherapy demonstrate 9.5% (cisplatin) and 41.3% (paclitaxel) tumor radius decrease.
Conclusion:
Interdisciplinary approach evaluating gold nanoparticle cytotoxicity and diffusive transport may provide insight into cancer nanotherapy.
Insights
This study developed a computational model for cancer nanotherapy, showing gold nanoparticles significantly improve drug delivery and efficacy compared to free drugs in complex tumor environments.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Computational Biology
Background:
- Clinical translation of cancer nanotherapy is hindered by complex parameter interactions.
- Optimizing nanomedicine requires understanding nano/drug/tumor/patient dynamics.
Purpose of the Study:
- To develop an interdisciplinary computational model for cancer nanotherapy.
- To investigate the diffusive transport of drug-loaded gold nanoparticles in tumors.
Main Methods:
- Evaluated lung cancer cell cytotoxicity using novel multi-layer gold nanoparticles with paclitaxel/cisplatin.
- Employed computer simulations, calibrated with in-vitro data, to model nanotherapy in heterogeneous tumors.
Main Results:
- Nanoparticles demonstrated significantly higher efficacy than free drugs.
- Simulations predicted substantial tumor radius reduction: 9.5% for cisplatin and 41.3% for paclitaxel.
- Diffusive transport in tumors increases drug resistance.
Conclusions:
- An interdisciplinary approach modeling nanoparticle cytotoxicity and diffusive transport offers insights into cancer nanotherapy.
- This modeling framework can aid in optimizing nanomedicine for clinical application.
