Long-term multimodal imaging of tumor draining sentinel lymph nodes using mesoporous silica-based nanoprobes

Abstract

The imaging of sentinel lymph nodes (SLNs), the first defense against primary tumor metastasis, has been considered as an important strategy for noninvasive tracking tumor metastasis in clinics. In this study, we report the development and application of mesoporous silica-based triple-modal nanoprobes that integrate multiple functional moieties to facilitate near-infrared optical, magnetic resonance (MR) and positron emission tomography (PET) imaging. After embedding near-infrared dye ZW800, the nanoprobe was labeled with T1 contrast agent Gd3+ and radionuclide 64Cu through chelating reactions. High stability and long intracellular retention time of the nanoprobes was confirmed by in vitro characterization, which facilitate long-term in vivo imaging. Longitudinal multimodal imaging was subsequently achieved to visualize tumor draining SLNs up to 3 weeks in a 4T1 tumor metastatic model. Obvious differences in uptake rate, amount of particles, and contrast between metastatic and contralateral sentinel lymph nodes were observed. These findings provide very helpful guidance for the design of robust multifunctional nanomaterials in SLNs’ mapping and tumor metastasis diagnosis.

Functionalized nanomaterials: their use as contrast agents in bioimaging: mono- and multimodal approaches

“…Dyedoped silica NPs are usually synthesized by a sol-gel Stöber process or in microemulsion by simply adding the dye (or a modified form of the dye) to the silica-forming solution. [123] In addition, the use of mesoporous silica NPs enables the loading of an additional functions into the resulting pores, for example imaging probes of sentinel lymph nodes (SLNs) known as the first defense against primary tumor metastasis, [124] sensing [125] or a therapeutic agent capable of photothermal ablation or a controlled drug release [126]. The covalent chemical grafting of lanthanide complexes on metal oxide nanoparticles was also recently performed and introduction of two different lanthanides gave bimodal contrast agents [64,65,127].…”

“…Common isotopes that can be chelated on to or incorporated within NPs (in an analogous way to the gadolinium ions used for MRI) include 18 F, 11 C, 15 O, 13 N, 64 Cu, 124 I, 68 Ga, 82 Rb, and 86 Y. PET imaging using 18 F, which is the most widespread radionuclide probe used in this field, has become an established clinical tool for whole-body imaging.…”

Functionalized nanomaterials: their use as contrast agents in bioimaging: mono- and multimodal approaches

“…The hollow MnO NPs could also Table 1 List of commonly used bioimaging techniques (partly adapted from Refs [50] and [51] High spatial resolution High Low sensitivity, cannot follow many labels, time consuming PET NPs incorporating radioisotopes (e.g., 18 F, 11 C, 64 Cu, 124 …”

“…The dye-doped silica NPs are usually synthesized by a sol-gel St ö ber process or in microemulsion by simply adding the dye (or a modified form of the dye) to the silicaforming solution [123] . In addition, the use of mesoporous silica NPs enables the loading of additional functions into the resulting pores, for example, the imaging probes of sentinel lymph nodes (SLNs) known as the first defense against primary tumor metastasis [124] , sensing [125] , or a therapeutic agent capable of photothermal ablation (PTA) or a controlled drug release [126] . The covalent chemical grafting of the lanthanide complexes on the metal oxide NPs was also recently performed, and the introduction of two different lanthanides gave bimodal CAs [64,65,127] .…”

“…Common isotopes that can be chelated onto or incorporated within NPs (in an analogous way to the gadolinium ions used for MRI) include 18 F, 11 C, 15 O, 13 N, 64 Cu, 124 I, 68 Ga, 82 Rb, and 86 Y. PET imaging using 18 F, which is the most widespread radionuclide probe used in this field, has become an established clinical tool for whole-body imaging.…”