Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An osmium-peroxo complex for photoactive therapy of hypoxic tumors.

ABSTRACT: The limited therapeutic effect on hypoxic and refractory solid tumors has hindered the practical application of photodynamic therapy. Herein, we report our investigation of an osmium-peroxo complex (Os2), which is inactive in the dark, but can release a peroxo ligand O₂^•- upon light irradiation even in the absence of oxygen, and is transformed into a cytotoxic osmium complex (Os1). Os1 is cytotoxic in the presence or absence of irradiation in hypoxic tumors, behaving as a chemotherapeutic drug. At the same time, the light-activated Os2 induces photocatalytic oxidation of endogenous 1,4-dihydronicotinamide adenine dinucleotide in living cancer cells, leading to ferroptosis, which is mediated by glutathione degradation, lipid peroxide accumulation and down-regulation of glutathione peroxidase 4. In vivo studies have confirmed that the Os2 can effectively inhibit the growth of solid hypoxic tumors in mice. A promising strategy is proposed for the treatment of hypoxic tumors with metal-based drugs.

SUBMITTER: Lu N

PROVIDER: S-EPMC9042834 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

An osmium-peroxo complex for photoactive therapy of hypoxic tumors.

Lu Nong N Deng Zhihong Z Gao Jing J Liang Chao C Xia Haiping H Zhang Pingyu P

Nature communications 20220426 1

The limited therapeutic effect on hypoxic and refractory solid tumors has hindered the practical application of photodynamic therapy. Herein, we report our investigation of an osmium-peroxo complex (Os2), which is inactive in the dark, but can release a peroxo ligand O<sub>2</sub><sup>•-</sup> upon light irradiation even in the absence of oxygen, and is transformed into a cytotoxic osmium complex (Os1). Os1 is cytotoxic in the presence or absence of irradiation in hypoxic tumors, behaving as a c ...[more]

PMID: 35473926

Similar Datasets

Breaking the barrier: an osmium photosensitizer with unprecedented hypoxic phototoxicity for real world photodynamic therapy.

Project description:Hypoxia presents a two-fold challenge in the treatment of cancer, as low oxygen conditions induce biological changes that make malignant tissues simultaneously more aggressive and less susceptible to standard chemotherapy. This paper reports the first metal-based photosensitizer that approaches the ideal properties for a phototherapy agent. The Os(phen)2-based scaffold was combined with a series of IP-nT ligands, where phen = 1,10-phenanthroline and IP-nT = imidazo[4,5-f][1,10]phenanthroline tethered to n = 0-4 thiophene rings. Os-4T (n = 4) emerged as the most promising complex in the series, with picomolar activity and a phototherapeutic index (PI) exceeding 106 in normoxia. The photosensitizer exhibited an unprecedented PI > 90 (EC50 = 0.651 μM) in hypoxia (1% O2) with visible and green light, and a PI > 70 with red light. Os-4T was also active with 733 nm near-infrared light (EC50 = 0.803 μM, PI = 77) under normoxia. Both computation and spectroscopic studies confirmed a switch in the nature of the lowest-lying triplet excited state from triplet metal-to-ligand charge transfer (3MLCT) to intraligand charge transfer (3ILCT) at n = 3, with a lower energy and longer lifetime for n = 4. All compounds in the series were relatively nontoxic in the dark but became increasingly phototoxic with additional thiophenes. These normoxic and hypoxic activities are the largest reported to date, demonstrating the utility of osmium for phototherapy applications. Moreover, Os-4T had a maximum tolerated dose (MTD) in mice that was >200 mg kg-1, which positions this photosensitizer as an excellent candidate for in vivo applications.

| S-EPMC7953430 | biostudies-literature

Enhancing Visible Light Absorption of Yellow-Colored Peroxo-Titanate Nanotubes Prepared Using Peroxo Titanium Complex Ions.

Project description:Visible light-activated yellow titanate nanotubes (TNTs) modified by peroxo groups were directly synthesized via a facile chemical reaction route using peroxo titanium complex ions as a precursor. Obtained peroxo-modified TNTs (PTNTs) possessed a cylindrical-shaped tubular morphology with an outer diameter of approximately 10 nm. The peroxo titanium functional group (Ti-O-O) was formed between the interlayers of the lepidocrocite-type titanate crystal that was the base structure of TNTs, with the interlayer distance estimated at approximately 10.02 Å. The formation of the peroxo functional groups reduced the electron density adjacent to the titanium atom, raising the valence band to 1.35 eV and forming a band gap of 2.50 eV, which is lower than that of TNTs (3.19 eV). In addition, the peroxo titanium functional group had a negative potential, which increased the chemical adsorption performances with positively charged rhodamine B molecules in water. Meanwhile, the photocatalytic investigation indicated that the PTNTs have enhanced the photocatalytic performance for RhB decolorization under visible light irradiating in comparison with TNTs. These findings show not only the improvement in the photocatalytic performance but also the potential of processing design by selecting the precursor with arbitrary characteristics.

| S-EPMC7469391 | biostudies-literature

Oxygen tension regulating nanoformulation for the improved photodynamic therapy of hypoxic tumors.

Project description:The clinical efficacy of photodynamic therapy (PDT) is hampered by the low oxygen tension highly prevalent in solid tumors. Hence, improving the oxygen tension by suppling hyperbaric oxygen (HBO), through oxygen delivery nanoarchitectures or by designing in situ oxygen-generating nanoenzymes is considered a robust approach for PDT that involves type II photosensitizers (PS). In this study, we successfully synthesized 4-arm chlorin-polylactide (CPLA) conjugates from meta-tetra-3-hydroxymethyl phenyl chlorin (m-THMPC) and D, L-lactide via ring opening polymerization (ROP), that could assemble into stable NPs, for the delivery of molecular oxygen into inner regions of hypoxic tumors (HTs). The monodispersed Air-CPLA-NPs prevented the PS, chlorin, from aggregation-induced quenching and loss of signal. Moreover, the Air-CPLA-NPs produced a marked level of intracellular ROS or 1O2 upon light irradiation (660 ± 10 nm, 20 J/cm2) which is indispensable for the prolonged and efficient PDT of HTs. The confocal laser scanning microscopy (CLSM) images revealed the gradual cellular internalization of Air-CPLA-NPs in hypoxic H1299 cells. It unveiled significant dose-dependent in vitro cytotoxicity towards normoxic and hypoxic H1299 cells. Furthermore, the in vivo anticancer study displayed the tumor growth inhibition (TGI) effect of Air-CPLA-NPs + PDT in normoxic and hypoxic xenograft mice models. Accordingly, the present architecture improved the PDT efficacy by overcoming the oxygen barrier in the inner tissues of HTs demonstrating the prospect of CPLA-NPs as an "oxygen shuttle" for the clinical PDT of solid tumors.

| S-EPMC11910142 | biostudies-literature

A monomeric Mn(III)-peroxo complex derived directly from dioxygen.

Project description:The binding and activation of dioxygen by transition metal complexes is a fundamentally and practically important process in chemistry. Often the initial steps involve formation of peroxometal species that is difficult to observe because of their inherent reactivity. The interaction of dioxygen with a manganese(II) complex (1) of bis[(N'-tert-butylurealy)-N-ethyl]-(6-pivalamido-2-pyridylmethyl)amine was investigated, leading to the detection of a new intermediate that is a peroxomanganese(III) complex (2). This complex is high-spin (S = 2) with a g value of 8.2 and D = -2.0(5) as determined by parallel-mode electron paramagnetic resonance spectroscopy. The coordination of a peroxo ligand was established using Fourier transform infrared spectroscopy that reveals a new signal at 885 cm-1 for 2 when formed from 16O2-this band shifts to 837 cm-1 when 18O2 is used in the preparation. Moreover, electrospray ionization mass spectra contain a strong ion at an m/z of 576.2703 for the 16O-isotopomer that shifts to 580.2794 in the 18O-isotopomer. Complex 2 also is capable of oxidatively deformylating aldehydes, which is a known reaction of peroxometal complexes. The similarities of 2 to the peroxo intermediates in cytochrome P450 are noted.

| S-EPMC2647946 | biostudies-literature

Theranostic Liposomes with Hypoxia-Activated Prodrug to Effectively Destruct Hypoxic Tumors Post-Photodynamic Therapy.

Project description:Photodynamic therapy (PDT), a noninvasive cancer therapeutic method triggered by light, would lead to severe tumor hypoxia after treatment. Utilizing a hypoxia-activated prodrug, AQ4N, which only shows toxicity to cancer cells under hypoxic environment, herein, a multipurpose liposome is prepared by encapsulating hydrophilic AQ4N and hydrophobic hexadecylamine conjugated chlorin e6 (hCe6), a photosensitizer, into its aqueous cavity and hydrophobic bilayer, respectively. After chelating a 64Cu isotope with Ce6, the obtained AQ4N-64Cu-hCe6-liposome is demonstrated to be an effective imaging probe for in vivo positron emission tomography, which together with in vivo fluorescence and photoacoustic imaging uncovers efficient passive homing of those liposomes after intravenous injection. After being irradiated with the 660 nm light-emitting diode light, the tumor bearing mice with injection of AQ4N-hCe6-liposome show severe tumor hypoxia, which in turn would trigger activation of AQ4N, and finally contributes to remarkably improved cancer treatment outcomes via sequential PDT and hypoxia-activated chemotherapy. This work highlights a liposome-based theranostic nanomedicine that could utilize tumor hypoxia, a side effect of PDT, to trigger chemotherapy, resulting in greatly improved efficacy compared to conventional cancer PDT.

| S-EPMC5372701 | biostudies-literature

Targeting Hypoxic Tumors with Hybrid Nanobullets for Oxygen-Independent Synergistic Photothermal and Thermodynamic Therapy.

Project description:Hypoxia is a feature of solid tumors and it hinders the therapeutic efficacy of oxygen-dependent cancer treatment. Herein, we have developed all-organic oxygen-independent hybrid nanobullets ZPA@HA-ACVA-AZ for the "precise strike" of hypoxic tumors through the dual-targeting effects from surface-modified hyaluronic acid (HA) and hypoxia-dependent factor carbonic anhydrase IX (CA IX)-inhibitor acetazolamide (AZ). The core of nanobullets is the special zinc (II) phthalocyanine aggregates (ZPA) which could heat the tumor tissues upon 808-nm laser irradiation for photothermal therapy (PTT), along with the alkyl chain-functionalized thermally decomposable radical initiator ACVA-HDA on the side chain of HA for providing oxygen-independent alkyl radicals for ablating hypoxic cancer cells by thermodynamic therapy (TDT). The results provide important evidence that the combination of reverse hypoxia hallmarks CA IX as targets for inhibition by AZ and synergistic PTT/TDT possess incomparable therapeutic advantages over traditional (reactive oxygen species (ROS)-mediated) cancer treatment for suppressing the growth of both hypoxic tumors and their metastasis.

| S-EPMC8012440 | biostudies-literature

Intervalence Charge Transfer in an Osmium(IV) Tetra(ferrocenylaryl) Complex.

Project description:The functional properties of tetraaryl compounds, M(aryl)4 (M = transition metal or group 14 element), are dictated not only by their common tetrahedral geometry but also by their central atom. The identity of this atom may serve to modulate the reactivity, electrochemical, magnetic, and optical behavior of the molecular species, or of extended materials built from appropriate tetraaryl building blocks, but this has not yet been systematically evaluated. Toward this goal, here we probe the influence of Os(IV), C, and Si central atoms on the spectroelectrochemical properties of a series of redox-active tetra(ferrocenylaryl) complexes. We prepare these compounds through Negishi cross-coupling from brominated precursors and confirm, through single-crystal X-ray diffraction, they exhibit comparable molecular structures with only small differences attributable to their dissimilar M-aryl bond lengths. Solution voltammetric and spectroelectrochemical studies reveal that access to mixed-valence states is uniquely provided by the Os(IV) species, which also exhibits a near-IR absorption band that is characteristic of intervalence charge transfer processes. Together, this work serves to highlight the remarkable electrochemical stability and distinct electronic properties of the Os(aryl)4 unit, as well as the potential utility of these and other M(aryl)4 species as modular building blocks for three-dimensional polymers or functional molecular devices.

| S-EPMC11815827 | biostudies-literature

Chromium(IV)-peroxo complex formation and its nitric oxide dioxygenase reactivity.

Project description:The O(2) and NO reactivity of a Cr(II) complex bearing a 12-membered tetraazamacrocyclic N-tetramethylated cyclam (TMC) ligand, [Cr(II)(12-TMC)(Cl)](+) (1), and the NO reactivity of its peroxo derivative, [Cr(IV)(12-TMC)(O(2))(Cl)](+) (2), are described. By contrast to the previously reported Cr(III)-superoxo complex, [Cr(III)(14-TMC)(O(2))(Cl)](+), the Cr(IV)-peroxo complex 2 is formed in the reaction of 1 and O(2). Full spectroscopic and X-ray analysis revealed that 2 possesses side-on ?(2)-peroxo ligation. The quantitative reaction of 2 with NO affords a reduction in Cr oxidation state, producing a Cr(III)-nitrato complex, [Cr(III)(12-TMC)(NO(3))(Cl)](+) (3). The latter is suggested to form via a Cr(III)-peroxynitrite intermediate. [Cr(II)(12-TMC)(NO)(Cl)](+) (4), a Cr(II)-nitrosyl complex derived from 1 and NO, could also be synthesized; however, it does not react with O(2).

| S-EPMC3496875 | biostudies-literature

Manganese porphyrin-based metal-organic framework for synergistic sonodynamic therapy and ferroptosis in hypoxic tumors.

Project description:Development of efficient therapeutic strategy to incorporate ultrasound (US)-triggered sonodynamic therapy (SDT) and ferroptosis is highly promising in cancer therapy. However, the SDT efficacy is severely limited by the hypoxia and high glutathione (GSH) in the tumor microenvironment, and ferroptosis is highly associated with reactive oxygen species (ROS) and GSH depletion. Methods: A manganese porphyrin-based metal-organic framework (Mn-MOF) was constructed as a nanosensitizer to self-supply oxygen (O2) and decrease GSH for enhanced SDT and ferroptosis. In vitro and in vivo analysis, including characterization, O2 generation, GSH depletion, ROS generation, lipid peroxidation, antitumor efficacy and tumor immune microenvironment were systematically evaluated. Results: Mn-MOF exhibited catalase-like and GSH decreasing activity in vitro. After efficient internalization into cancer cells, Mn-MOF persistently catalyzed tumor-overexpressed H2O2 to in-situ produce O2 to relieve tumor hypoxia and decrease GSH and GPX4, which facilitated the formation of ROS and ferroptosis to kill cancer cells upon US irradiation in hypoxic tumors. Thus, strong anticancer and anti-metastatic activity was found in H22 and 4T1 tumor-bearing mice after a single administration of Mn-MOF upon a single US irradiation. In addition, Mn-MOF showed strong antitumor immunity and improved immunosuppressive microenvironment upon US irradiation by increasing the numbers of activated CD8+ T cells and matured dendritic cells and decreaing the numbers of myeloid-derived suppressor cells in tumor tissues. Conclusions: Mn-MOF holds great potential for hypoxic cancer therapy.

| S-EPMC7778611 | biostudies-literature

Effects of Annealing Temperature on the Crystal Structure, Morphology, and Optical Properties of Peroxo-Titanate Nanotubes Prepared by Peroxo-Titanium Complex Ion.

Project description:This study addresses the effects of annealing temperatures (up to 500 °C) on the crystal structure, morphology, and optical properties of peroxo groups (-O-O-) containing titanate nanotubes (PTNTs). PTNTs, which possess a unique tubular morphology of layered-compound-like hydrogen titanate structure (approximately 10 nm in diameter), were synthesized using peroxo-titanium (Ti-O-O) complex ions as a precursor under very mild conditions-temperature of 100 °C and alkali concentration of 1.5 M-in the precursor solution. The nanotubular structure was dismantled by annealing and a nanoplate-like structure within the range of 20-50 nm in width and 100-300 nm in length was formed at 500 °C via a nanosheet structure by decreasing the specific surface area. Hydrogen titanate-based structures of the as-synthesized PTNTs transformed directly into anatase-type TiO2 at a temperature above 360 °C due to dehydration and phase transition. The final product, anatase-based titania nanoplate, was partially hydrogen titanate crystal in nature, in which hydroxyl (-OH) bonds exist in their interlayers. Therefore, the use of Ti-O-O complex ions contributes to the improved thermal stability of hydrogen titanate nanotubes. These results show a simple and environmentally friendly method that is useful for the synthesis of functional nanomaterials for applications in various fields.

| S-EPMC7407109 | 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