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基于全肺图谱的单细胞水平上纳米颗粒和肿瘤的跨尺度示踪。

Cross-scale tracing of nanoparticles and tumors at the single-cell level using the whole-lung atlas.

机构信息

Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

University of Chinese Academy of Sciences, Beijing 100049, China.

出版信息

Sci Adv. 2023 Aug 2;9(31):eadh7779. doi: 10.1126/sciadv.adh7779.

DOI:10.1126/sciadv.adh7779
PMID:37531437
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10396308/
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.

摘要

目前，肿瘤异质性限制了肿瘤治疗的效果，这给纳米靶向药物输送系统（DDS）的发展带来了巨大挑战。因此，解决肿瘤与纳米颗粒之间的时空相互作用非常重要。然而，由于整体器官尺度和亚细胞精度之间存在差距，粒子可视化限制了靶向评估。在这里，提出了一种基于微光学切片断层成像（MOST）系统和荧光 MOST（fMOST）系统的高精度肿瘤结构三维（3D）可视化方法，以阐明肿瘤内纳米颗粒的 3D 空间分布。我们证明，通过 MOST/fMOST 系统，可以揭示肿瘤结构和纳米颗粒分布之间的多维和跨尺度相关性，从而重塑肿瘤微环境并探索血管结构参数。与现有方法相比，这种可视化方法为肿瘤治疗的 DDS 的疗效、分布和靶向效率提供了更准确的评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad06/10396308/0946baa391c0/sciadv.adh7779-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad06/10396308/b9c99db105e9/sciadv.adh7779-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad06/10396308/077b3050b445/sciadv.adh7779-f5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad06/10396308/0946baa391c0/sciadv.adh7779-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad06/10396308/b9c99db105e9/sciadv.adh7779-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad06/10396308/9c255318b6a7/sciadv.adh7779-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad06/10396308/a5a102d8dcf8/sciadv.adh7779-f3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad06/10396308/077b3050b445/sciadv.adh7779-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad06/10396308/1a0feda23c10/sciadv.adh7779-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad06/10396308/0946baa391c0/sciadv.adh7779-f7.jpg

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