Development of Non-Porous Silica Nanoparticles towards Cancer Photo-Theranostics

Abstract

Nanoparticles have demonstrated several advantages for biomedical applications, including for the development of multifunctional agents as innovative medicine. Silica nanoparticles hold a special position among the various types of functional nanoparticles, due to their unique structural and functional properties. The recent development of silica nanoparticles has led to a new trend in light-based nanomedicines. The application of light provides many advantages for in vivo imaging and therapy of certain diseases, including cancer. Mesoporous and non-porous silica nanoparticles have high potential for light-based nanomedicine. Each silica nanoparticle has a unique structure, which incorporates various functions to utilize optical properties. Such advantages enable silica nanoparticles to perform powerful and advanced optical imaging, from the in vivo level to the nano and micro levels, using not only visible light but also near-infrared light. Furthermore, applications such as photodynamic therapy, in which a lesion site is specifically irradiated with light to treat it, have also been advancing. Silica nanoparticles have shown the potential to play important roles in the integration of light-based diagnostics and therapeutics, termed "photo-theranostics". Here, we review the recent development and progress of non-porous silica nanoparticles toward cancer "photo-theranostics".

Keywords: imaging; nonporous; organically modified silica (ORMOSIL) nanoparticles; organosilica nanoparticles; silica nanoparticles; theranostics; therapy.

Figure 1

Schematic structure of three types of silica nanoparticles.

Figure 2

Single-cell dual-particle images showing macrophage uptake of fluorescent organosilica nanoparticles surface functionalized with PEG. The macrophages were incubated with a mixture of Flu and Rho (A) or with a mixture of Flu-PEG30K and Rho (B). The fluorescence images of Rub (R), Flu, or Flu-PEG30K (F) and merged images (M) of single cells are shown, from 0 to 6 h. The scale bars represent 40 μm. (A1,A2) Cells showed similar uptake of Flu and Rho. (B1,B2) Cells showed uptake of Rho and almost no uptake of Flu-PEG30K. (B3,B4) Cells showed uptake of Rho and a lower uptake of Flu-PEG30K. (B5,B6) Cells showed a similar uptake of Flu, Rho, and Flu-PEG30K. Reproduced with permission from Nakamura, M.; Hayashi, K.; Nakano, M.; Kanadani, T.; Miyamoto, K.; Kori, T.; Horikawa, K. Identification of polyethylene glycol-resistant macrophages on stealth imaging in vitro using fluorescent organosilica nanoparticles. ACS Nano 2015, 9, 1058–1071 [127].

Figure 3

Depth-dependent NIR fluorescence in vivo imaging of a tumor. (A) A schematic illustration of depth-dependent NIR fluorescence imaging. Longer excitation and emission wavelengths, such as 745/840 nm (Ex745/Em850), can penetrate tissue very well and can detect particles in deeper sites, compared to shorter wavelengths (i.e., Ex710/Em760 and Ex640/Em700). (B) We administered totals of 2 mg (Day 1) and 6 mg (Day 10) of thiol-OS/IR820 into a mouse that had a subcutaneous xenograft tumor intravenously and observed the fluorescence using the in vivo imaging system under three excitation/emission wavelength conditions (Ex640/Em700 nm, Ex710/Em760 nm, and Ex745/Em840 nm). Reproduced with permission from Nakamura, M.; Hayashi, K.; Nakamura, J.; Mochizuki, C.; Murakami, T.; Miki, H.; Ozaki, S.; Abe, M. Near-Infrared Fluorescent Thiol-Organosilica Nanoparticles That are Functionalized with IR-820 and Their Applications for Long-Term Imaging of in Situ Labeled Cells and Depth-Dependent Tumor in Vivo Imaging. Chem. Mater. 2020, 32, 7201–7214 [106].

Figure 4

In vivo HER2-targeted PET imaging in xenograft breast cancer models. Serial coronal and axial tomographic PET images acquired at 2, 24, 48, and 72 h post intravenous injection of radiolabeled particle immunoconjugates in groups of tumor-bearing mice (N = 5 for each group), as follows: (A) targeted group, ⁸⁹Zr-DFO-scFv-PEG-Cy5-C dots in BT-474 mice; (B) non-targeted group, ⁸⁹Zr-DFO-Ctr/scFv-PEG-Cy5-C dots in BT-474 mice; and (C) targeted group, ⁸⁹Zr-DFOscFv-PEG-Cy5-C dots in MDA-MB-231 mice. For each group, maximum intensity projection (MIP) images were also acquired at 48 h p.i. H, heart; B, bladder; L, liver. All BT-474 tumors are marked with yellow arrows, while all MDA-MB-231 tumors are marked with red arrows. Reproduced with permission from Chen, F.; Ma, K.; Madajewski, B.; Zhuang, L.; Zhang, L.; Rickert, K.; Marelli, M.; Yoo, B.; Turker, M.Z.; Overholtzer, M.; et al. Ultrasmall targeted nanoparticles with engineered antibody fragments for imaging detection of HER2-overexpressing breast cancer. Nat. Commun. 2018, 9, 1–11 [87].