In Situ Imaging of Cellular Reactive Oxygen Species and Caspase-3 Activity Using a Multifunctional Theranostic Probe for Cancer Diagnosis and Therapy

Abstract

In this work, a multifunctional theranostic nanoprobe (Au–Ag-HM) was skillfully designed for simultaneous imaging of intracellular reactive oxygen species (ROS) and caspase-3 activity. The Au–Ag-HM was fabricated by coloading of silver nanoparticles (AgNPs) and hematoporphyrin monomethyl ether (HMME) to Au nanoflowers (AuNFs). When Au–Ag-HM was devoured by cancer cells, HepG2 cells were used as the model, and under laser irradiation, the photogenerated intracellular ROS by the photosensitizer HMME would induce the apoptosis of cancer cells. Meanwhile, the intracellular ROS triggered the oxidative etching of AgNPs on Au–Ag-HM, which led to a tremendous localized surface plasmon resonance response and scattering color changes in Au–Ag-HM, allowing in situ dark-field imaging of the ROS level in cancer cells. On the other hand, the ROS-induced activation of cellular caspase-3, which cleaved the C-peptide-containing caspase-3-specific recognition sequence (DEVD) and allowed HMME to release from the nanoprobe, resulted in a significant fluorescence recovery related to caspase-3 activity. Both photogenerated ROS and enhanced caspase-3 activity contributed to the synergistic effect of laser-mediated chemotherapy and photodynamic therapy. Therefore, the as-prepared theranostic probe could be used for simultaneous detection of cellular ROS and caspase-3 activity, distinguishing between tumor cells and normal cells, inducing the apoptosis of cancer cells, and providing a new method for diagnosis and therapy of cancer.

Preparation of triangular silver nanoparticles and their biological effects in the treatment of ovarian cancer

“…The WB results showed increased caspase-3 expression in the cells treated with tAgNPs. Relevant studies have shown that AgNPs activate caspase-3 and promote cell apoptosis, thereby inhibiting tumour growth [ 37 , 38 ] . Studies have confirmed that AgNPs increase the caspase-3 level in breast cancer [ 39 ], lung cancer [ 40 ] and other cancers, indicating that tAgNP-treated OC cells complete the apoptosis process through the cysteine protease pathway.…”

Nanotechnologies for Reactive Oxygen Species“Turn-On” Detection

“…Distinct from the design of nanotechnologies for selective sensing of specific species of ROS, these nanomaterials can detect the combined species of ROS by one platform. Several nanomaterials, including PEGylated bilirubin-coated superparamagnetic iron oxide nanoparticles (PEG-BR@SPIONs) ( Lee et al, 2020 ), UCNPs-MoS 2 nanoflakes ( Wang F. et al, 2018 ), multifunctional theranostic nanoprobes (Au−Ag-HM) ( Wang et al, 2021 ), para-aminothiophenol and hemin-decorated gold (Au-PATP-Hemin) nanoprobes ( Cui et al, 2018 ), cyclotriphosphazene-doped graphene quantum dots (C-GQDs) ( Xu et al, 2020 ), ROS-responsive microgel ( Liu et al, 2018 ), and the ionic nanoparticles in a hydrogel microparticle ( Liu et al, 2018 ), are designed under this context. Therein, PEG-BR@SPIONs and Au-PATP-Hemin nanoprobe are promising tools for “turn-on” detection of ROS with demonstrated mechanisms and have potentialities in biological applications.…”

Design of a Ratiometric Plasmonic Biosensor for Herceptin Detection in HER2-Positive Breast Cancer

“…The valuable characteristics of AuNPs, such as their simplicity of synthesis and various surface functionalization mechanisms indicating why gold nanoparticles, are an attractive candidate for further improvement in the clinical diagnosis method, which is thoroughly described in a review article by Gambhir . AuNP-based nanobiosensors are developed as substitutes and facile tools for improving highly sensitive biosensors because of their proper conjugation procedure and superior optical and electrical features. ,− Also, the LSPR-based technique receives promoting interest because of its wide applications in catalysis, phototherapy, and cellular imaging. − In these tools, when AuNPs with particular decorating groups identify their targets, the interaction between both molecules causes a local deviation in the refractive index at the metal surface, which can be screened by spectrometric analysis.…”