In Vivo Targeted Cancer Imaging, Sentinel Lymph Node Mapping and Multi-Channel Imaging with Biocompatible Silicon Nanocrystals

Abstract

Quantum dots (QDs) have size-dependent optical properties that make them uniquely advantageous for in vivo targeted fluorescence imaging, traceable delivery, and therapy. The use of group II-VI (e.g., CdSe) QDs for these applications is advancing rapidly. However, group II-VI QDs contain toxic heavy metals that limit their in vivo applications. Thus, replacing these with QDs of a biocompatible semiconductor, such as silicon (Si), is desirable. Here, we demonstrate that properly encapsulated biocompatible Si QDs can be used in multiple cancer-related in vivo applications, including tumor vasculature targeting, sentinel lymph node mapping, and multicolor NIR imaging in live mice. This work overcomes dispersibility and functionalization challenges to in vivo imaging with Si QDs through a unique nanoparticle synthesis, surface functionalization, PEGylated micelle encapsulation, and bioconjugation process that produces bright, targeted nanospheres with stable luminescence and long (>40 h) tumor accumulation time in vivo. Upon the basis of this demonstration, we anticipate that Si QDs can play an important role in more sophisticated in vivo models, by alleviating QD toxicity concerns while maintaining the key advantages of QD-based imaging methods.

Ultra-small fluorescent inorganic nanoparticles for bioimaging

“…30 In addition to in vitro labelling cells, Si NPs can also be used in multiple cancer-related in vivo applications, including tumor vasculature targeting, sentinel lymph node mapping, and multicolor NIR imaging in live mice. 206 Erogbogbo and coworkers demonstrated that Si NPs can overcome dispersibility 35 and functionalization challenges for in vivo imaging through surface functionalization, PEGylated micelle encapsulation, and bioconjugation process, which produced bright, targeted nanospheres with stable luminescence and long (>40 h) tumor accumulation time in vivo. Recently, the biodistribution and 40 toxicity of Si NPs in mice and monkeys have been assessed (Figure 23).…”

Quantum Dots-Based Biological Fluorescent Probes for In Vitro and In Vivo Imaging

“…Significantly, such micelle-encapsulated SiQDs kept stable optical properties under various biologically relevant conditions of pH values (4-10) and temperatures (20-70 o C) [59]. The micelle-encapsulated SiQDs were further used in multiple cancer-related in vivo applications, including tumor vasculature targeting, sentinel lymph node mapping, and multicolor imaging in live mice [60]. Tilley and coworkers systematically investigated the chemical reactions on molecules attached to the surface of SiQDs, and further developed a multi-stepped chemical method for surface modification of SiQDs [61].…”

Cationic Silicon Nanocrystals with Colloidal Stability, pH‐Independent Positive Surface Charge and Size Tunable Photoluminescence in the Near‐Infrared to Red Spectral Range

“…Steric stabilization strategies typically use long poly(ethylene glycol) chains to achieve colloidal stability. The use of solid lipid nanoparticles by Henderson et al and phospholipid micelles by Erogbogbo et al are prime examples 13, 14, 15. Electrostatic stabilization strategies rely on ionic ligands to prevent flocculation, commonly used ones include olefins with terminal carboxylic acids and terminal primary amines 8, 12, 15, 16, 17, 18, 19, 20.…”

“…For example, ncSi based on steric stabilization strategies typically have larger hydrodynamic diameters ranging from 20 to 100 nm, and incorporates many ncSi in one nanoparticle, whereas ncSi based on electrostatic strategies typically have diameters below 5 nm and are dispersible as isolated nanocrystals 12, 15, 17, 21. In general, hydrodynamic diameters below about 5 nm are desirable since nanoparticles below this threshold can be cleared through urinary excretion to minimize potential toxicity effects 4…”