Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

All-in-one mitochondria-targeted NIR-II fluorophores for cancer therapy and imaging.

ABSTRACT: Small-molecule subcellular organelle-targeting theranostic probes are crucial for early disease diagnosis and treatment. The imaging window of these molecules is mainly focused on the visible and near-infrared region (below ∼900 nm) which limits the tissue penetration depth and therapeutic effects. Herein, a novel NIR-II small-molecule probe H4-PEG-Glu with a thiopyrylium cation was synthesized. H4-PEG-Glu not only can quickly and effectively image mitochondria in acute myeloid leukemia (AML) cells, and induce G₀/G₁ phase arrest by the intrinsic mitochondrial apoptosis pathway w/o irradiation, but also exhibit moderate cytotoxicity against AML cancer cells in a dose dependent-manner without laser irradiation. The THP-1 cells treated with H4-PEG-Glu upon NIR laser irradiation showed enhanced chemo- and photothermal therapy (CPTT) with 93.07% ± 6.43 apoptosis by Annexin V staining. Meanwhile, H4-PEG-Glu displayed high synergistic CPTT effects in vivo, as well as specific NIR-II tumor imaging in AML patient derived PDX mouse models for the first time. Our work lays down a solid foundation for designing small-molecule NIR-II mitochondria-selective theranostic probes.

SUBMITTER: Zheng Y

PROVIDER: S-EPMC8179124 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Upconversion NIR-II fluorophores for mitochondria-targeted cancer imaging and photothermal therapy.

Project description:NIR-II fluorophores have shown great promise for biomedical applications with superior in vivo optical properties. To date, few small-molecule NIR-II fluorophores have been discovered with donor-acceptor-donor (D-A-D) or symmetrical structures, and upconversion-mitochondria-targeted NIR-II dyes have not been reported. Herein, we report development of D-A type thiopyrylium-based NIR-II fluorophores with frequency upconversion luminescence (FUCL) at ~580 nm upon excitation at ~850 nm. H4-PEG-PT can not only quickly and effectively image mitochondria in live or fixed osteosarcoma cells with subcellular resolution at 1 nM, but also efficiently convert optical energy into heat, achieving mitochondria-targeted photothermal cancer therapy without ROS effects. H4-PEG-PT has been further evaluated in vivo and exhibited strong tumor uptake, specific NIR-II signals with high spatial and temporal resolution, and remarkable NIR-II image-guided photothermal therapy. This report presents the first D-A type thiopyrylium NIR-II theranostics for synchronous upconversion-mitochondria-targeted cell imaging, in vivo NIR-II osteosarcoma imaging and excellent photothermal efficiency.

| S-EPMC7713230 | biostudies-literature

A mitochondria-targeted molecular phototheranostic platform for NIR-II imaging-guided synergistic photothermal/photodynamic/immune therapy.

Project description:Phototherapy is a conducive and non-invasive strategy for cancer therapy under light irradiation. Inspiringly, fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) holds a great promise for imaging-guided phototherapy with deep penetration and high spatiotemporal resolution. However, most phototherapeutics still face great challenges, including complicated synthesis of agents, potential biotoxicity and unsatisfied therapeutic outcomes. Herein, a near-infrared laser triggered molecular photosensitizer FEPT, modified with triphenylphosphine PEGylation (PEG2000-TPP), is developed for NIR-II imaging-guided mitochondria-targeting synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/immune therapy (IMT). The mitochondria-targeting photosensitizer FEPT can produce reactive oxygen species (ROS) and hyperpyrexia upon 808 nm laser irradiation, resulting in mitochondrial dysfunction and photo-induced apoptosis via caspase-3 pathway. Phototherapy-induced hyperthermia or ROS triggers the release of immunogenic intracellular substrates from dying tumor cells, thereby promoting the activation of antitumor immunity. Herein, this work provides a practicable strategy to develop a molecular phototheranostic platform for imaging-guided cancer therapy via mitochondria-targeting.

| S-EPMC9652787 | biostudies-literature

Novel benzo-bis(1,2,5-thiadiazole) fluorophores for <i>in vivo</i> NIR-II imaging of cancer.

Project description:Optical imaging of diseases represents a highly dynamic and multidisciplinary research area, and second near-infrared window (NIR-II, 1000-1700 nm) imaging is at the forefront of the research on optical imaging techniques. Small-molecule based NIR-II (1000-1700 nm) dyes are highly promising candidates for in vivo molecular imaging because of their high biocompatibility, fast excretion, and high clinical translation ability. However, research reports on small-molecule based NIR-II dyes and probes are rare. Herein, we designed a series of fluorescent compounds (Q1, Q2, Q3, and Q4) and investigated the relationships between their structures and absorption/fluorescence properties. Q4 (maximum emission at 1100 nm) stood out as the dye with the best physical properties and thus was selected as a scaffold for the facile construction of two types of water-soluble and biocompatible NIR-II probes (Q4NPs and SCH1100). Highly specific gastrin-releasing peptide receptor (GRPR) targeted NIR-II imaging of prostate cancer in living mice was achieved using the small-molecule probe SCH1100, which represents the first small peptide based NIR-II probe for targeted cancer imaging. The attractive imaging properties of Q4-based NIR-II probes open up many opportunities for molecular imaging and clinical translation in the unique NIR-II window.

| S-EPMC6024204 | biostudies-literature

A New Green Titania with Enhanced NIR Absorption for Mitochondria-Targeted Cancer Therapy.

Project description:A new kind of green titania (G-TiO2-x ) with obvious green color was facilely synthesized from black titania (B-TiO2-x ) through subsequently strong ultrasonication. Comparatively, this stable G-TiO2-x shows much enhanced near infrared (NIR) absorption, especially around 920 nm, which can be ascribed to the obvious change of TiO2-x lattice order owing to the effect of ultrasonication. This feature enables G-TiO2-x to be stimulated with 980 nm laser in the combined photodynamic therapy (PDT) and photothermal therapy (PTT), which is greatly beneficial for improving tissue penetration depth. Furthermore, since mitochondria are preferred subcellular organelles for PDT/PTT, G-TiO2-x was further designed to conjugate with triphenylphosphonium (TPP) ligand for mitochondria-targeted PDT/PTT to obtain precise cancer treatment. Attributing to the high mitochondria-targeting efficiency and simultaneously synergistic PDT/PTT, high phototherapeutic efficacy and safety with a much lower laser power density (980 nm, 0.72 W cm-2) and low materials dosage were achieved both in vitro and in vivo. In addition, negligible toxicity was found, indicating high biocompatibility. This novel G-TiO2-x could provide new strategies for future precise minimal/non-invasive tumor treatment.

| S-EPMC5436512 | biostudies-literature

3D NIR-II Molecular Imaging Distinguishes Targeted Organs with High-Performance NIR-II Bioconjugates.

Project description:Greatly reduced scattering in the second near-infrared (NIR-II) region (1000-1700 nm) opens up many new exciting avenues of bioimaging research, yet NIR-II fluorescence imaging is mostly implemented by using nontargeted fluorophores or wide-field imaging setups, limiting the signal-to-background ratio and imaging penetration depth due to poor specific binding and out-of-focus signals. A newly developed high-performance NIR-II bioconjugate enables targeted imaging of a specific organ in the living body with high quality. Combined with a home-built NIR-II confocal set-up, the enhanced imaging technique allows 900 µm-deep 3D organ imaging without tissue clearing techniques. Bioconjugation of two hormones to nonoverlapping NIR-II fluorophores facilitates two-color imaging of different receptors, demonstrating unprecedented multicolor live molecular imaging across the NIR-II window. This deep tissue imaging of specific receptors in live animals allows development of noninvasive molecular imaging of multifarious models of normal and neoplastic organs in vivo, beyond the traditional visible to NIR-I range. The developed NIR-II fluorescence microscopy will become a powerful imaging technique for deep tissue imaging without any physical sectioning or clearing treatment of the tissue.

| S-EPMC5931222 | biostudies-literature

A mitochondrial-targeted prodrug for NIR imaging guided and synergetic NIR photodynamic-chemo cancer therapy.

Project description:Nontoxic prodrugs, especially activated by tumor microenvironment, are urgently required for reducing the side effects of cancer therapy. And combination of chemo-photodynamic therapy prodrugs show effectively synergetic therapeutic efficiency, however, this goal has not been achieved in a single molecule. In this work, we developed a mitochondrial-targeted prodrug PNPS for near infrared (NIR) fluorescence imaging guided and synergetic chemo-photodynamic precise cancer therapy for the first time. PNPS contains a NIR photosensitizer (NPS) and an anticancer drug 5'-deoxy-5-fluorouridine (5'-DFUR). These two parts are linked and caged through a bisboronate group, displaying no fluorescence and very low cytotoxicity. In the presence of H2O2, the bisboronate group is broken, resulting in activation of NPS for NIR photodynamic therapy and activation of 5'-DFUR for chemotherapy. The activated NPS can also provide a NIR fluorescence signal for monitoring the release of activated drug. Taking advantage of the high H2O2 concentration in cancer cells, PNPS exhibits higher cytotoxicity to cancer cells than normal cells, resulting in lower side effects. In addition, based on its mitochondrial-targeted ability, PNPS exhibits enhanced chemotherapy efficiency compare to free 5'-DFUR. It also demonstrated a remarkably improved and synergistic chemo-photodynamic therapeutic effect for cancer cells. Moreover, PNPS exhibits excellent tumor microenvironment-activated performance when intravenously injected into tumor-bearing nude mice, as demonstrated by in vivo fluorescence imaging. Thus, PNPS is a promising prodrug for cancer therapy based on its tumor microenvironment-activated drug release, synergistic therapeutic effect and "turn-on" NIR imaging guide.

| S-EPMC5861986 | biostudies-literature

NIR-II and visible fluorescence hybrid imaging-guided surgery via aggregation-induced emission fluorophores cocktails.

Project description:Fluorescence imaging-guided surgery is one of important techniques to realize precision surgery. Although second near-infrared window (NIR-II) fluorescence imaging has the advantages of high resolution and large penetration depth in surgical navigation, its major drawback is that NIR-II images cannot be detected by our naked eyes, which demands a high hand-eye coordination for surgeons and increases the surgical difficulty. On the contrary, visible fluorescence can be observed by our naked eyes but has poor penetration. Here, we firstly propose a kind of NIR-II and visible fluorescence hybrid navigation surgery assisted via a cocktail of aggregation-induced emission nanoparticles (AIE NPs). NIR-II imaging helps to locate deep targeted tissues and judge the residual, and visible fluorescence offers an easily surgical navigation. We apply this hybrid navigation mode in different animals and systems, and verify that it can accelerate surgical process and compatible with a visible fluorescence endoscopy. To deepen the understanding of lymph node (LN) labelling, the distribution of NPs in LNs after local administration is initially analyzed by NIR-II fluorescence wide-filed microscopy, and two fates of the NPs are summarized. An alternative strategy which combines indocyanine green and berberine is also reported as a compromise for rapidly clinical translation.

| S-EPMC9424606 | biostudies-literature

Anti-quenching NIR-II molecular fluorophores for in vivo high-contrast imaging and pH sensing.

Project description:The contrast and sensitivity of in vivo fluorescence imaging has been revolutionized by molecular fluorophores operating in the second near-infrared window (NIR-II; 1000-1700 nm), but an ongoing challenge is the solvatochromism-caused quenching in aqueous solution for the long-wavelength absorbing fluorophores. Herein, we develop a series of anti-quenching pentamethine cyanine fluorophores that significantly overcome the severe solvatochromism, thus affording stable absorption/emission beyond 1000 nm with up to ~ 44-fold enhanced brightness and superior photostability in aqueous solution. These advantages allow for deep optical penetration (8 mm) as well as high-contrast and highly-stable lymphatic imaging superior to clinical-approved indocyanine green. Additionally, these fluorophores exhibit pH-responsive fluorescence, allowing for noninvasive ratiometric fluorescence imaging and quantification of gastric pH in vivo. The results demonstrate reliable accuracy in tissue as deep as 4 mm, comparable to standard pH electrode method. This work unlocks the potential of anti-quenching pentamethine cyanines for NIR-II biological applications.

| S-EPMC6401027 | biostudies-literature

NIR-II emissive donor-acceptor-donor fluorophores for dual fluorescence bioimaging and photothermal therapy applications.

Project description:Fluorescence bioimaging with near-infrared II (NIR-II) emissive organic fluorophores has proven to be a viable noninvasive diagnostic technique. However, there is still the need for the development of fluorophores that possess increased stability as well as functionalities that impart stimuli responsiveness. Through strategic design, we can synthesize fluorophores that possess not only NIR-II optical profiles but also pH-sensitivity and the ability to generate heat upon irradiation. In this work, we employ a donor-acceptor-donor (D-A-D) design to synthesize a series of NIR-II fluorophores. Here we use thienothiadiazole (TTD) as the acceptor, 3-hexylthiophene (HexT) as the π-spacer and vary the alkyl amine donor units: N,N-dimethylaniline (DMA), phenylpiperidine (Pip), and phenylmorpholine (Morp). Spectroscopic analysis shows that all three derivatives exhibit emission in the NIR-II region with λemimax ranging from 1030 to 1075 nm. Upon irradiation, the fluorophores exhibited noticeable heat generation through non-radiative processes. The ability to generate heat indicates that these fluorophores will act as theranostic (combination therapeutic and diagnostic) agents in which simultaneous visualization and treatment can be performed. Additionally, biosensing capabilities were supported by changes in the absorbance properties while under acidic conditions as a result of protonation of the alkyl amine donor units. The fluorophores also show minimal toxicity in a human mammary cell line and with murine red blood cells. Overall, initial results indicate viable NIR-II materials for multiple biomedical applications.

| S-EPMC10955863 | biostudies-literature

Pancreas-targeted NIR fluorophores for dual-channel image-guided abdominal surgery.

Project description:ObjectivePancreas-related complications are some of the most serious ones in abdominal surgery. The goal of this study was to develop and validate novel near-infrared (NIR) fluorophores that would enable real-time pancreas imaging to avoid the intraoperative pancreatic injury.DesignAfter initial screening of a large NIR fluorophore library, the performance of 3 selected pancreas-targeted 700 nm NIR fluorophores, T700-H, T700-F, and MB, were quantified in mice, rats, and pigs. Dose ranging using 25 and 100 nmol, and 2.5 µmol of T700-F, and its imaging kinetics over a 4 h period were tested in each species. Three different 800 nm NIR fluorophores were employed for dual-channel FLARE™ imaging in pigs: 2 μmol of ZW800-1 for vessels and kidney, 1 μmol of ZW800-3C for lymph nodes, and 2 μmol of ESNF31 for adrenal glands.ResultsT700-F demonstrated the highest signal to background ratio (SBR), with peak SBR at 4 h postinjection in mice. In pigs, T700-F produced an SBR≥2 against muscle, spleen, and lymph nodes for up to 8 h after a single intravenous injection. The combination of T700-F with each 800 nm NIR fluorophore provided simultaneous dual-channel intraoperative imaging of pancreas with surrounding organs in real time.ConclusionPancreas-targeted NIR fluorophores combined with the FLARE dual-channel imaging system enable the real-time intraoperative pancreas imaging which helps surgeons perform safer and more curative abdominal surgeries.

| S-EPMC4265744 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data