Dual-Targeted Gold Nanoprism for Recognition of Early Apoptosis, Dual-Model Imaging and Precise Cancer Photothermal Therapy

Abstract

Photothermal therapy as novel strategy to convert near-infrared (NIR) light into heat for treatment cancers has attracted great attention and been widely studied. However, side effects and low efficiency remain the main challenge of precise cancer photothermal therapy.Methods: In this study, we have successfully fabricated and characterized the dual-targeted gold nanoprisms, whereby bare gold nanoprisms (Au NPR) were conjugated to a phenanthroline derivatives-functionalized tetraphenylethene (TPE) and further stabilized with target peptide aptamers via Au-S bonds (Au-Apt-TPE). Then, the remaining nitrogen atoms of the Au-Apt-TPE could effectively chelate with Zn2+ ions (Au-Apt-TPE@Zn) for monitoring early stage apoptotic cells.Results: The as-synthesized Au-Apt-TPE@Zn exhibited good monodispersity, size stability and consistent spectral characteristics. TPE synthesized here showed aggregation-induced emission (AIE) characteristics, and zinc conjunction (TPE@Zn) endowed Au-Apt-TPE@Zn with the cell membrane-targeted ability to selectively recognize the membranes of early stage apoptotic cells but not respond to healthy cells, which provided valuable diagnosis information on therapeutic efficacy. Au-Apt-TPE@Zn achieved specifically nuclear-targeted ability by surface decoration of AS1411 DNA aptamer. Au-Apt-TPE@Zn under NIR irradiation showed effective photothermal therapy against SGC-7901 human gastric carcinoma cells growth in vitro by inducing apoptosis through triggering reactive oxygen species (ROS) overproduction and regulating multiple signal crosstalk. In vivo studies revealed that Au-Apt-TPE@Zn under NIR irradiation showed deep penetration and dual-model imaging application (cancer-targeted fluorescence imaging and light-up photoacoustic imaging). Au-Apt-TPE@Zn under NIR irradiation also displayed strong photothermal therapy against gastric carcinoma xenograft growth in vivo by induction of apoptosis. Importantly, analysis of histopathology, hematotoxicity and immunocytotoxicity indicated that Au-Apt-TPE@Zn had less side effect and high biocompatibility.Conclusions: Our findings validated the design of using Au nanoprism with AIE materials and dual-targeted decoration could be an effective strategy in recognition of early apoptosis, dual-model imaging and precise cancer photothermal therapy.

Cannabinoid WIN 55,212-2 Inhibits Human Glioma Cell Growth by Triggering ROS-Mediated Signal Pathways

“…ROS is an important factor in inducing apoptosis [ 30 ]. Studies have confirmed that ROS generation was an early apoptotic event, which can be detected as early as 5 min [ 31 – 33 ]. Loss of mitochondrial membrane potential, opening of mitochondrial permeability transition pore (MPTP), and drug metabolism all contribute to the ROS generation [ 31 – 33 ].…”

“…Studies have confirmed that ROS generation was an early apoptotic event, which can be detected as early as 5 min [ 31 – 33 ]. Loss of mitochondrial membrane potential, opening of mitochondrial permeability transition pore (MPTP), and drug metabolism all contribute to the ROS generation [ 31 – 33 ]. In this study, it was found that WIN induced ROS production during U251 cell apoptosis, which triggered nonspecific signals in the downstream region and activated caspase-3 which leads to ultimately apoptosis, and this was further confirmed by the antioxidant GSH.…”

Synthesis and Application of AS1411-Functionalized Gold Nanoparticles for Targeted Therapy of Gastric Cancer

“…In a recent study, Zhang et al reported that a zinc-tetraphenylethene dual-targeted gold nanoprism provided strong photothermal therapy against SGC-7901 human gastric cancer cell growth. 34 Gold nanomaterials had been demonstrated to absorb NIR light and then induce DNA dehybridization. 35 It is worth noting that gold nanoshells absorb NIR light energy and increase their surface temperature to achieve ssDNA release at or near 37 °C with little or no temperature increase of the local environment.…”

Ruthenium-loaded mesoporous silica as tumor microenvironment-response nano-fenton reactors for precise cancer therapy

“…ROS-mediated oxidative stress as an early apoptotic event was located at the upstream of MAPKs and PI3K/AKT pathways. Studies have verified that dysfunction of MAPKs and PI3K/AKT pathways both contributed to nano-drugs-induced anticancer mechanisms [ 34 – 36 ]. Hence, the status of MAPKs and PI3K/AKT pathways in Ru@SiO 2 -PA-treated SGC-7901 cells was evaluated by western blot analysis.…”