Cross-scale tracing of nanoparticles and tumors at the single-cell level using the whole-lung atlas
Zeying Cao1,2, Yanli Zhao3, Hongyu Sun1
1Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Abstract:
Currently, the effectiveness of oncotherapy is limited by tumor heterogeneities, which presents a huge challenge for the development of nanotargeted drug delivery systems (DDSs). Therefore, it is important to resolve the spatiotemporal interactions between tumors and nanoparticles. However, targeting evaluation has been limited by particle visualization due to the gap between whole-organ scale and subcellular precision. Here, a high-precision three-dimensional (3D) visualization of tumor structure based on the micro-optical sectioning tomography (MOST) system and fluorescence MOST (fMOST) system is presented to clarify 3D spatial distribution of nanoparticles within the tumor. We demonstrate that through the MOST/fMOST system, it is possible to reveal multidimensional and cross-scale correlations between the tumor structure and nanoparticle distribution to remodel the tumor microenvironment and explore the structural parameters of vasculature. This visualization methodology provides an accurate assessment of the efficacy, distribution, and targeting efficiency of DDSs for oncotherapy compared to available approaches.
Insights
This study presents a novel 3D visualization technique using micro-optical sectioning tomography (MOST) and fluorescence MOST (fMOST) to precisely map nanoparticle distribution within tumors. This advancement aids in evaluating drug delivery systems for cancer therapy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Tumor heterogeneity limits cancer therapy effectiveness and challenges nanoparticle drug delivery.
- Accurate visualization of nanoparticle distribution is crucial for evaluating targeted drug delivery systems (DDSs).
- Current methods lack the precision to bridge whole-organ and subcellular scales for nanoparticle tracking.
Purpose of the Study:
- To develop a high-precision 3D visualization method for assessing nanoparticle distribution within tumors.
- To clarify the spatiotemporal interactions between tumor structures and nanoparticles.
- To provide an accurate evaluation of DDS efficacy, distribution, and targeting efficiency.
Main Methods:
- Utilized micro-optical sectioning tomography (MOST) and fluorescence MOST (fMOST) systems.
- Generated high-precision three-dimensional (3D) reconstructions of tumor structures.
- Visualized the 3D spatial distribution of nanoparticles within the tumor microenvironment.
Main Results:
- Demonstrated the capability of MOST/fMOST to reveal cross-scale correlations between tumor structure and nanoparticle distribution.
- Enabled exploration of structural parameters of tumor vasculature.
- Provided a visualization methodology for accurate assessment of DDS efficacy and targeting.
Conclusions:
- The MOST/fMOST system offers unprecedented precision for visualizing nanoparticle behavior in tumors.
- This technique facilitates a deeper understanding of tumor-nanoparticle interactions.
- It represents a significant advancement in evaluating and optimizing nanoparticle-based cancer therapies.
