ABSTRACT
Colorectum cancer has become one of the most fatal cancer diseases, in which NAD(P)H: quinone oxidoreductase 1 (NQO1) plays a role in intracellular free radical reduction and detoxification and has been linked to colorectum cancer and chemotherapy resistance. Therefore, rational design of optical probe for NQO1 detection is urgent for the early diagnosis of colorectum cancer. Herein, we have developed a novel two-photon fluorescent probe, WHFD, which is capable of selectively detecting of intracellular NQO1 with two-photon (TP) absorption (800 nm) and near-infrared emission (620 nm). Combination with a substantial Stokes shift (175 nm) and biocompatibility, we have assessed its suitability for in vivo imaging of endogenous NQO1 activities from HepG2 tumor-bearing live animals with high tissue penetration up to 300 µm. Particularly, we for the first time used the probe to image NQO1 activities from human colorectum cancer samples by using TP microscopy, and proving our probe possesses reliable diagnostic performance to directly in situ imaging of cancer biomarker and can clearly distinguish the boundary between human colorectum cancer tissue and their surrounding normal tissue, which shows great potential for the intraoperative navigation.
Subject(s)
Colorectal Neoplasms , Fluorescent Dyes , NAD(P)H Dehydrogenase (Quinone) , Photons , NAD(P)H Dehydrogenase (Quinone)/metabolism , NAD(P)H Dehydrogenase (Quinone)/analysis , Humans , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/pathology , Animals , Hep G2 Cells , Optical Imaging , Infrared Rays , Mice , Mice, NudeABSTRACT
Due to their inherent advantages, silica nanoparticles (SiNPs) have greatly potential applications as bioactive materials in biosensors/biomedicine. However, the long-term and nonspecific accumulation in healthy tissues may give rise to toxicity, thereby impeding their widespread clinical application. Hence, it is imperative and noteworthy to develop biodegradable and clearable SiNPs for biomedical purposes. Recently, the design of multi-stimuli responsive SiNPs to improve degradation efficiency under specific pathological conditions has increased their clinical trial potential as theranostic nanoplatform. This review comprehensively summaries the rational design and recent progress of biodegradable SiNPs under various internal and external stimuli for rapid in vivo degradation and clearance. In addition, the factors that affect the biodegradation of SiNPs are also discussed. We believe that this systematic review will offer profound stimulus and timely guide for further research in the field of SiNP-based nanosensors/nanomedicine.
Subject(s)
Nanoparticles , Silicon Dioxide , Silicon Dioxide/chemistry , Nanoparticles/chemistry , Humans , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Biosensing Techniques/methods , Theranostic NanomedicineABSTRACT
C-Jun N-terminal kinase (JNK) is a key mediator involved in a variety of physiological processes. JNK activation is regulated in a complex manner by upstream kinases and phosphatases, and plays an important role in physiological processes such as the immune response and neuronal function. Therefore, JNK has become a therapeutic target for neurodegenerative diseases, ankylosing spondylitis, psoriasis, arthritis and other diseases. Inhibition of JNK activation in mitochondria holds great potential for Parkinson's disease (PD) therapy. However, no specific mitochondrial-targeted JNK inhibitor has been reported. We have developed a mitochondrial-targeted JNK inhibitor, P2, by linking a mitochondrial-specific cell-penetrating peptide to SP600125 (SP), a commercialized specific inhibitor of JNK. We found that P2 specifically inhibited mitochondrial JNK phosphorylation instead of nuclear JNK signaling. Further studies showed that P2 effectively rescued PD phenotypes both inâ vitro and inâ vivo, thus indicating that it is a potential therapeutic for PD.
Subject(s)
Parkinson Disease , Humans , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Phosphorylation , MAP Kinase Signaling System/physiology , JNK Mitogen-Activated Protein Kinases/metabolism , JNK Mitogen-Activated Protein Kinases/pharmacology , Mitochondria/metabolismABSTRACT
Histamine released by activated basophils has become an important biomarker and therapeutic target in the development of allergic diseases. To date, several gold nanoparticle (AuNP)-based nanosensors have been reported for histamine detection in foods. However, rapid, highly sensitive and direct detection of histamine in allergic diseases is still lacking due to the complexity of the physical environment. Herein, we developed a novel nanosensor for colorimetric visualization of histamine in activated basophils by simply coupling dithiobis(succinimidylpropionate) (DSP) on the surface of AuNPs (DSP-AuNPs). The DSP moiety serves as a linker and can react with the aliphatic amino group of histamine, and the imidazole ring of histamine can selectively bind with Au by means of p-p conjugation, thus inducing the aggregation of AuNPs. In this study, we experimentally proved that DSP-AuNPs showed good sensitivity and selectivity to histamine among various amino acids, including histidine. Additionally, this nanosensor displayed a rapid response to histamine with a linear range of 0.8-2.5 µM, and the limit of detection (LOD) was 0.014 µM, which is a relatively low LOD in comparison with those of other AuNP-based nanosensors. Finally, DSP-AuNPs are used, for the first time, to successfully detect endogenous histamine changes in activated basophils. Therefore, our work may provide a promising strategy to monitor histamine levels in the basophil activation test.