Sequential deconstruction of composite drug transport in metastatic breast cancer

Area of Science:

• Biomedical Engineering
• Oncology
• Nanotechnology

Background:

• Targeting metastatic breast cancer (MBC) with drug delivery systems (DDS) is challenging due to inadequate imaging and analysis of DDS-metastasis interactions.
• Effective strategies for DDS delivery and retention within metastatic lesions are crucial for improving therapeutic outcomes.

Purpose of the Study:

• To systematically deconstruct the trafficking of injectable nanoparticle generators (iNPG-pDox) within pulmonary MBC using a multidisciplinary imaging and modeling approach.
• To provide improved drug delivery strategies for MBC by understanding DDS-lesion dynamics.

Main Methods:

• Integration of in vivo PET-CT, ex vivo optical imaging, and confocal microscopy for multiscale analysis.
• Utilized mathematical modeling and simulations to analyze nanoparticle distribution and retention.
• Investigated the impact of lesion size and microenvironment on DDS accumulation.

Main Results:

• Injectable nanoparticle generators (iNPG-pDox) showed substantial accumulation in metastatic lungs compared to healthy lungs.
• Intratumoral distribution and retention of iNPG-pDox were influenced by metastatic lesion size and the tumor microenvironment.
• Multiscale imaging and simulations provided insights into DDS transport dynamics within metastases.

Conclusions:

• Developed a translational toolbox integrating advanced imaging and mathematical modeling to evaluate DDS-metastasis interactions.
• The findings offer a framework for rationally designing advanced therapies for metastatic cancers.
• Understanding DDS trafficking within metastases is key to optimizing drug delivery for improved MBC treatment.