Sandwich-Structured Upconversion Nanoprobes Coated with a Thin Silica Layer for Mitochondria-Targeted Cooperative Photodynamic Therapy for Solid Malignant Tumors

Abstract

Upconversion nanoparticles-based photodynamic nanotheranostic agents (UCNPs-PDT) have received great interest due to improved tissue penetration, weak autofluorescence, and low biotoxicity. However, conventional UCNPs-PDT are often limited by low energy transfer efficiency from UCNPs to photosensitizer (PS) molecules and insufficient generation and limited diffusion distance of reactive oxygen species (ROSs). Herein, an “all in one” nanotheranostic agent has been developed which has multicolor sandwich-structured UCNPs (SWUCNPs) as the core, a thin silica layer with a mitochondria-targeted group for loading dual PS as the medium layer, and polyethylene glycol–folic acid (PEG-FA) chains as the outer layer. Multicolor SWUCNPs simultaneously achieve two-photon fluorescence imaging and serve as energy donor for dual PS molecules. The thin luminescence layer and silica layer control most UCNPs activators and PS molecules in the effective energy transfer distance to guarantee a high energy transfer efficiency. Via FA-mediated endocytosis, the nanotheranostic agent is selectively endocytosed by cancer cells, is released from the endosome/lysosome, targets the mitochondria, and in situ produces ROSs under excitation from NIR, leading to significant mitochondria-mediated cell apoptosis. Furthermore, the established nanotheranostic agent shows tumor targetability, increased generation of ROSs, high PDT efficacy, significant cell apoptosis, minimal systemic cytotoxicity, and efficacious in vivo tumor inhibition.

Nucleic Acids Analysis

“…Owing to the high stability, low cost, and convenient labeling, nanoparticles can also serve as signal probes for DNA detection to further improve the performance of sandwich assays [106][107][108][109][110][111][112][113][114][115]. For example, Zhang et al [116] reported a nanoparticle based "sandwich" detection strategy by immobilizing gold nanoparticles (AuNPs) with reporter probes that flank the target nucleic acids.…”

Construction of Multicolor Upconversion Nanotheranostic Agent for in-situ Cooperative Photodynamic Therapy for Deep-Seated Malignant Tumors

“…To process the CCK-8 assay, MCF-7 cancer cells cultured in the 96-well-microtiter plates were incubated with the obtained nanotheranostic agent (70 µg/mL). After 12 h, MCF-7 cancer cells were washed with PBS buffer, excited under the NIR laser and then incubated for another 24 h. Afterward, the CCK-8 agent (10 µL) was added into each pore and incubated cells for 2 h. Finally, the microplate reader was used to record the absorbance of MCF-7 cancer cells at 450 nm (Yue et al, 2018;Song et al, 2019).…”

“…After treatment, MCF-7 cancer cells were collected, stained with apoptosis staining solution for 5.0 min (500 µL binding buffer, 6 µL Annexin V-FITC staining solution and 7 µL PE staining solution) and then injected for flow cytometry analysis. Based on the manufacturer's instruction, the necessary fluorescence compensation was adjusted (Song et al, 2019).…”

“…Under the excitation of NIR, UCNPs would excite ICG molecules, which would further transfer their excited energy to emitters ions, thus the luminescence efficiency of UCNPs was enhanced, which was beneficial for the further excitation of PS molecules and the improvement of the photodynamic efficacy. The thin silica layer would assist the sensitization function of ICG and the activation of triple PS molecules (Yue et al, 2018;Song et al, 2019). Thus, ICG as PS molecules and NIR sensitizer could effectively enhance PDT efficacy.…”

<p>Up-Conversion Luminescent Nanoparticles for Molecular Imaging, Cancer Diagnosis and Treatment</p>

“…UCNPs have been used in different molecular tests including cell and wholebody fluorescent imaging (for instance vascular imaging, 36,37 lymph node imaging, 38 and targeted cancer imaging 39 ). Previous studies have shown that UCNPs coated with different ligands (silica shells, 40 charged polymers, 41 active small molecules, 42 biomacromolecules, 43 etc.) and/or covalently linked to functional groups (peptides, 44 folates, 45 antibodies, 46 etc.)…”