Nitric Oxide-Activated “Dual-Key–One-Lock” Nanoprobe for in Vivo Molecular Imaging and High-Specificity Cancer Therapy

Citations Over TimeTop 10% of 2019 papers

Abstract

Cancer treatments are confounded by severe toxic effects toward patients. To address these issues, activatable nanoprobes have been designed for specific imaging and destruction of cancer cells under the stimulation of specific cancer-associated biomarkers. Most activatable nanoprobes were usually activated by some single-factor stimulation, but this restricts therapeutic specificity between diseased and normal tissue; therefore, multifactor activation is highly desired. To this end, we herein develop a novel dual-stimuli responsive theranostic nanoprobe for simultaneously activatable cancer imaging and photothermal therapy under the coactivation of "dual-key" stimulation of "nitric oxide (NO)/acidity", so as to further improve the therapeutic specificity. Specifically, we have integrated a weak electron acceptor (benzo[c][1,2,5]thiadiazole-5,6-diamine) into a donor-π-acceptor-π-donor type chromophore. When the weak acceptor was oxidized by NO in acidic conditions to form a stronger acceptor (5H-[1,2,3]triazolo[4,5-f]-2,1,3-benzothiadiazole), the molecule absorption was significantly increased in the near-infrared region, based on the intramolecular charge transfer (ICT) mechanism. Under the dual-key stimulation of NO/acidity within the tumor associated with inflammation, the nanoprobe can correspondingly output dual signals for ratiometric photoacoustic and photothermal imaging of cancer in vivo and do so with enhanced accuracy and specificity. Our novel nanoprobe exhibited higher photoacoustic signal enhancement under dual-factor activation at 9.8 times that of NO and 132 times that of acidity alone, respectively. Moreover, through such dual activation of NO/acidity, the nanoprobe produces more differentiation of hyperthermia between tumor and normal tissues, to afford satisfactory photothermal therapy with minimal toxic side effects. Thus, our work presents a promising strategy for significantly improving the precision and specificity of cancer imaging and therapy.

Related Papers

• → Quantitative Assessment of Copper(II) in Wilson’s Disease Based on Photoacoustic Imaging and Ratiometric Surface-Enhanced Raman Scattering(2021)92 cited
• → A ratiometric fluorescent nanoprobe for H₂O₂sensing and in vivo detection of drug-induced oxidative damage to the digestive system(2014)47 cited
• → Ag nanobox/silica/CdTeS quantum dot nanoprobe with photoluminescence emission enhancement for labeling cancer cells(2018)5 cited
• → A biocompatible ratiometric fluorescent nanoprobe for intracellular hydrogen sulfide accurate detection based on rare earth nanoparticle(2022)4 cited
• → Cation Exchange Strategy to Construct a Targeting Nanoprobe for Enhanced Positive MR Imaging Capability(2020)