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Published on: July 2, 2020
Magnetic Resonance Imaging-Based Radiogenomic Analysis Reveals Genomic Determinants for Nanoparticle Delivery into
Di Liu1, Na Lu1, Fengchao Zang2
1State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 211102, P. R. China.
Abstract:
Even though the enhanced permeability and retention (EPR) effect is applicable for the passive targeting of solid tumors, many nanodrugs have failed to achieve meaningful clinical outcomes due to the heterogeneity of EPR effect. Therefore, understanding the mechanism of the EPR effect is crucial to overcome the obstacles nanomedicines face in clinical translation. The aim of this study was to establish a reliable method to increase awareness of the critical influencing factors of nanoparticle (NP) transport into tumors based on the EPR effect using a combined radiogenomics and clinical magnetic resonance imaging (MRI) technique and gene set pathway enrichment analysis. Employing poly(lactic-co-glycolic acid) (PLGA)-coated Fe3O4 NPs as the contrast agent, the monolayer and multilayer distribution of the NPs were observed and quantitatively analyzed by MRI, improving the accuracy of evaluating vascular permeability by MRI. By performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of genes and pathways, we identified a variety of genes affecting vascular permeability, such as Cldn1, Dlg2, Bves, Prkag3, Cldn10, and Cldn8, which are related to tight junctions and control the permeability of blood vessels in tumors. The method presented here provides an MRI-supported approach to increase the breadth of data collected from genetic screens, reveals genetic evidence of the presence of NPs in tumors and lays a foundation for clinical patient stratification and personalized treatment.
Insights
Understanding nanoparticle (NP) transport into tumors is key for nanomedicine. This study uses MRI and genomics to reveal genes controlling tumor vascular permeability, paving the way for personalized cancer treatments.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- The enhanced permeability and retention (EPR) effect is crucial for passive tumor targeting but is limited by its heterogeneity, hindering nanomedicine clinical translation.
- Identifying factors influencing nanoparticle (NP) delivery via the EPR effect is essential for improving nanodrug efficacy.
- Current methods lack the precision to fully characterize the complex factors governing NP transport in tumors.
Purpose of the Study:
- To develop a reliable method for assessing NP transport into tumors based on the EPR effect.
- To investigate the influence of genetic factors on tumor vascular permeability using a combined radiogenomics and MRI approach.
- To provide a foundation for clinical patient stratification and personalized nanomedicine treatments.
Main Methods:
- Utilized poly(lactic-co-glycolic acid) (PLGA)-coated iron oxide (Fe3O4) nanoparticles as MRI contrast agents.
- Employed quantitative magnetic resonance imaging (MRI) to analyze nanoparticle distribution and evaluate vascular permeability.
- Performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on tumor genetic data.
Main Results:
- Developed an MRI-based technique for accurate, quantitative assessment of nanoparticle distribution and vascular permeability.
- Identified key genes (e.g., Cldn1, Dlg2, Bves) influencing tumor vascular permeability, particularly those involved in tight junction regulation.
- Demonstrated the presence of nanoparticles within tumors using genetic screening data and MRI.
Conclusions:
- The combined radiogenomics and MRI approach offers a powerful tool for understanding EPR effect heterogeneity.
- This method enhances the ability to collect genetic data related to nanoparticle biodistribution in tumors.
- The findings support the development of patient stratification strategies for personalized nanomedicine therapies.
