Recent Development of Inorganic Nanoparticles for Biomedical Imaging

Abstract

Inorganic nanoparticle-based biomedical imaging probes have been studied extensively as a potential alternative to conventional molecular imaging probes. Not only can they provide better imaging performance but they can also offer greater versatility of multimodal, stimuli-responsive, and targeted imaging. However, inorganic nanoparticle-based probes are still far from practical use in clinics due to safety concerns and less-optimized efficiency. In this context, it would be valuable to look over the underlying issues. This outlook highlights the recent advances in the development of inorganic nanoparticle-based probes for MRI, CT, and anti-Stokes shift-based optical imaging. Various issues and possibilities regarding the construction of imaging probes are discussed, and future research directions are suggested.

Figure 1

Current status of inorganic nanoparticle-based bioimaging and future direction.

Figure 2

(a) Field-dependent magnetization (M–H) curves at 300 K for iron oxide nanoparticles of various sizes (left). Description of the spin canting effect in the iron oxide nanoparticles of various sizes (right). (b) In vivo MR images of the xenografted tumor before (left) and after (right) intravenous administration of FIONs. (c) Artifact filtering imaging agent (mAFIA) that comprises a combination of paramagnetic Gd-MOF and superparamagnetic nanoparticles for T₁–T₂ dual-mode MRI. (d) Tumor pH-responsive magnetic nanogrenades composed of self-assembled extremely small-sized iron oxide nanoparticles and pH-sensitive ligands. Reprinted with permission from refs (21, 38, 67), and (74). Copyright 2011, 2012, and 2014 American Chemical Society.

Figure 3

(a) X-ray attenuation factors of various elements. (b) Simulated attenuations of I, Yb, Ta, and Au against X-ray produced at 80 kVp (A), 100 kVp (B), 120 kVp (C), and 140 kVp (D). (c) Schematic illustration of RITC-doped tantalum oxide nanoparticles for multimodal imaging. (d) In vivo CT images (left) and optical images (right) of the sentinel lymph node of the rat 2 h after intradermal injection of RITC-doped tantalum oxide nanoparticles in both paws. Reprinted with permission from refs (29) and (82). Copyright 2011 American Chemical Society and 2015 RSNA.

Figure 4

(a) Energy diagram of ZnS:Mn nanoparticles excited by multiphoton absorption. Two-photon absorption of ZnS (600 nm) or Mn²⁺ (NIR-II region) induces orange emission. Three-photon absorption of ZnS also induces orange emission. (b) Two-photon image of FITC and three-photon image of ZnS:Mn nanoparticles. Three-photon imaging showed better spatial resolution. (c) Transmission spectra of tumor tissue and blood. The NIR-II region exhibits improved transmission. (d) PL intensity of ZnS:Mn nanoparticles at different excitation wavelengths. For comparison, Rhodamine 6G is measured at 900 nm. S is the slope of the linear fitting. Between 900 and 1000 nm, the excitation mechanism is a three-photon absorption, and between 1100 and 1180 nm, the excitation mechanism is switched to two-photon absorption. The efficiency of PL is highest when excited at 1180 nm. Reprinted with permission from refs (42), (97), and (101). Copyright 2013 Macmillan Publishers Limited and 2013 American Chemical Society.

Figure 5

(a) Left: The schematic of multi-dye-sensitized UCNPs for a broad range of light absorption. Three dye sensitizers (e.g., BODIPY-FL for blue absorption, Cy 3.5 for green absorption, and IR 806 for red absorption) are immobilized on the nanoparticles. Right: The energy diagram of the three sensitizers and the UCNPs. (b) Left: The schematic of Nd³⁺-doped core/shell UCNPs excited under 800 nm irradiation. Right: The energy diagram of the core/shell UCNPs. (c) NaLuF₄:Yb,Tm@NaGdF₄ (¹⁵³Sm) nanoparticles work as a multimodal imaging agent for upconversion luminescence imaging (Yb³⁺,Tm³⁺), CT (Lu³⁺,Yb³⁺), T₁ MRI (Gd³⁺), and SPECT (¹⁵³Sm³⁺). Reprinted with permission from refs (117, 125), and (139). Copyright 2017 Wiley and 2013 American Chemical Society.