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Updated: Feb 17, 2026
Biomolecular Imaging of Cellular Uptake of Nanoparticles using Multimodal Nonlinear Optical Microscopy
Published on: May 16, 2022
Microscopic investigation of" topically applied nanoparticles for molecular imaging of fresh tissue surfaces
Soyoung Kang1, Yu Winston Wang1, Xiaochun Xu2
1Department of Mechanical Engineering, University of Washington, Seattle, Washington.
Abstract:
Previous studies have shown that functionalized nanoparticles (NPs) topically applied on fresh tissues are able to rapidly target cell-surface protein biomarkers of cancer. Furthermore, studies have shown that a paired-agent approach, in which an untargeted NP is co-administered with a panel of targeted NPs, controls for the nonspecific behavior of the NPs, enabling quantitative imaging of biomarker expression. However, given the complexities in nonspecific accumulation, diffusion, and chemical binding of targeted NPs in tissues, studies are needed to better understand these processes at the microscopic scale. Here, fresh tissues were stained with a paired-agent approach, frozen, and sectioned to image the depth-dependent accumulation of targeted and untargeted NPs. The ratio of targeted-to-untargeted NP concentrations-a parameter used to distinguish between tumor and benign tissues-was found to diminish with increasing NP diffusion depths due to nonspecific accumulation and poor washout. It was then hypothesized and experimentally demonstrated that larger NPs would exhibit less diffusion below tissue surfaces, enabling higher targeted-to-untargeted NP ratios. In summary, these methods and investigations have enabled the design of NP agents with improved sensitivity and contrast for rapid molecular imaging of fresh tissues.
Insights
Functionalized nanoparticles (NPs) targeting cancer biomarkers show reduced effectiveness with depth due to nonspecific accumulation. Larger NPs improve targeted-to-untargeted ratios, enhancing molecular imaging sensitivity in fresh tissues.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Molecular Imaging
Background:
- Functionalized nanoparticles (NPs) can target cancer biomarkers on fresh tissues.
- A paired-agent approach with targeted and untargeted NPs enables quantitative imaging.
- Understanding NP diffusion and accumulation in tissues is crucial for accurate imaging.
Purpose of the Study:
- To investigate the depth-dependent accumulation of targeted and untargeted NPs in fresh tissues.
- To analyze the factors affecting the targeted-to-untargeted NP ratio.
- To optimize NP design for improved molecular imaging sensitivity and contrast.
Main Methods:
- Fresh tissues were stained using a paired-agent approach with targeted and untargeted NPs.
- Tissues were frozen and sectioned for microscopic imaging.
- Depth-dependent NP accumulation and concentration ratios were quantified.
Main Results:
- The ratio of targeted-to-untargeted NPs decreased with increasing diffusion depth.
- Nonspecific accumulation and poor washout contributed to diminished ratios.
- Larger NPs demonstrated reduced diffusion, leading to higher targeted-to-untargeted NP ratios.
Conclusions:
- Nonspecific NP accumulation limits the effectiveness of targeted NPs in deep tissues.
- NP size is a critical factor in controlling diffusion and improving imaging contrast.
- Optimized NP design enhances sensitivity for rapid molecular imaging of fresh tissues.
