Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dual Molecular Design toward a Lysosome-Tagged AIEgen and Heavy-Atom-Free Photosensitizers for Hypoxic Cancer Photodynamic Therapy.

ABSTRACT: To date, a large number of photosensitizers (PS) have introduced heavy atoms to improve the ISC process and ¹O₂ generation. However, they often show low efficiency in hypoxic conditions, aggregate states, and turn-off PDT in the dark. Besides that, the toxicity of heavy metals is also concerned. Therefore, we developed lysosome-targeted heavy-metal-free PS (3S and 4S) based on thionated naphthalimide for hypoxic cancer photodynamic therapy (PDT), not only under white light but also in the dark via thermal-induced ¹O₂ generation. AIEgen (3O and 4O) were prepared for studying the PDT action of PSs (3S and 4S) in lysosome and aggregate state. We also examined the photophysical properties of AIEgen (3O and 4O) and PS (3S and 4S) by UV-vis absorption, fluorescent emission spectra, and theoretical calculations.

SUBMITTER: Pham TC

PROVIDER: S-EPMC9221524 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Dual Molecular Design toward a Lysosome-Tagged AIEgen and Heavy-Atom-Free Photosensitizers for Hypoxic Cancer Photodynamic Therapy.

Pham Thanh Chung TC Hoang Thi Thuy Hang TTH Choi Yeonghwan Y Lee Seongman S Joo Sang-Woo SW Kim Gun G Kim Dongwon D Jung Ok-Sang OS Lee Songyi S

Biosensors 20220615 6

To date, a large number of photosensitizers (PS) have introduced heavy atoms to improve the ISC process and 1O2 generation. However, they often show low efficiency in hypoxic conditions, aggregate states, and turn-off PDT in the dark. Besides that, the toxicity of heavy metals is also concerned. Therefore, we developed lysosome-targeted heavy-metal-free PS (3S and 4S) based on thionated naphthalimide for hypoxic cancer photodynamic therapy (PDT), not only unde ...[more]

PMID: 35735567

Similar Datasets

Site-selected thionated benzothioxanthene chromophores as heavy-atom-free small-molecule photosensitizers for photodynamic therapy.

Project description:Photodynamic therapy is a clinically approved anticancer modality that employs a light-activated agent (photosensitizer) to generate cytotoxic reactive oxygen species (ROS). There is therefore a growing interest for developing innovative photosensitizing agents with enhanced phototherapeutic performances. Herein, we report on a rational design synthetic procedure that converts the ultrabright benzothioxanthene imide (BTI) dye into three heavy-atom-free thionated compounds featuring close-to-unit singlet oxygen quantum yields. In contrast to the BTI, these thionated analogs display an almost fully quenched fluorescence emission, in agreement with the formation of highly populated triplet states. Indeed, the sequential thionation on the BTI scaffold induces torsion of its skeleton reducing the singlet-triplet energy gaps and enhancing the spin-orbit coupling. These potential PSs show potent cancer-cell ablation under light irradiation while remaining non-toxic under dark condition owing to a photo-cytotoxic mechanism that we believe simultaneously involves singlet oxygen and superoxide species, which could be both characterized in vitro. Our study demonstrates that this simple site-selected thionated platform is an effective strategy to convert conventional carbonyl-containing fluorophores into phototherapeutic agents for anticancer PDT.

| S-EPMC9814739 | biostudies-literature

Single-atom replacement as a general approach towards visible-light/near-infrared heavy-atom-free photosensitizers for photodynamic therapy.

Project description:Photodynamic therapy has become an emerging strategy for the treatment of cancer. This technology relies on the development of photosensitizers (PSs) that convert molecular oxygen to cytotoxic reactive oxygen species upon exposure to light. In this study, we have developed a facile and general strategy for obtaining visible light/near-infrared-absorbing PSs by performing a simple sulfur-for-oxygen replacement within existing fluorophores. Thionation of carbonyl groups within existing fluorophore cores leads to an improvement of the singlet oxygen quantum yield and molar absorption coefficient at longer wavelengths (deep to 600-800 nm). Additionally, these thio-based PSs lack dark cytotoxicity but exhibit significant phototoxicity against monolayer cancer cells and 3D multicellular tumor spheroids with IC50 in the micromolar range. To achieve tumor-specific delivery, we have conjugated these thio-based PSs to an antibody and demonstrated their tumor-specific therapeutic activity.

| S-EPMC7473402 | biostudies-literature

Fine-tuning the electronic structure of heavy-atom-free BODIPY photosensitizers for fluorescence imaging and mitochondria-targeted photodynamic therapy.

Project description:Theranostics that combines both diagnosis and therapy into a single platform has recently emerged as a promising biomedical approach for cancer treatment; however, the development of efficient theranostic agents with excellent optical properties remains a challenge. Here, we report novel mitochondria-targeting BODIPY photosensitizers (R-BODs) that possess considerable singlet oxygen generation capabilities and good fluorescence properties for imaging-guided photodynamic therapy (PDT). The incorporation of sulfur atoms into the π-conjugated skeleton of BODIPY along with the introduction of different functional groups at the meso-position of the BODIPY core is essential for tuning the photophysical and photosensitizing properties. Notably, the MeOPh-substituted thiophene-fused BODIPY (MeO-BOD, R = p-methoxyphenyl) displayed the highest singlet oxygen generation capability (Φ Δ ≈ 0.85 in air-saturated acetonitrile) and a moderate fluorescence quantum yield (Φ f = 17.11). Furthermore, MeO-BOD showed good biocompatibility, low dark toxicity and superior fluorescence imaging properties in living cells. More importantly, the PDT efficacy of mitochondria-specific anchoring of MeO-BOD was remarkably amplified with an extremely low half-maximal inhibitory concentration (IC50) value of 95 nM. We believe that the incorporation of an electron-donating group at the meso-position of the thiophene-fused BODIPY platform may be an effective approach for developing theranostic agents for precision cancer therapy.

| S-EPMC8152625 | biostudies-literature

Efficient Photooxidation of Sulfides with Amidated Alloxazines as Heavy-atom-free Photosensitizers.

Project description:Photooxidation utilizing visible light, especially with naturally abundant O2 as the oxygen source, has been well-accepted as a sustainable and efficient procedure in organic synthesis. To ensure the intersystem crossing and triplet quantum yield for efficient photosensitization, we prepared amidated alloxazines (AAs) and investigated their photophysical properties and performance as heavy-atom-free triplet photosensitizers and compared with those of flavin (FL) and riboflavin tetraacetate (RFTA). Because of the difference in the framework structure of AAs and FL and the introduction of carbonyl moiety, the absorption of FL at ∼450 nm is blue-shifted to ∼380 nm and weakened (ε = 8.7 × 103 for FL to ∼6.8 × 103 M-1 cm-1), but the absorption at ∼340 nm is red-shifted to ∼350 nm and enhanced by ∼50% (from ε = 6.4 × 103 for FL to ∼9.9 × 103 M-1 cm-1) in AAs. The intersystem crossing rates from the S1 to T1 are also enhanced in these AAs derivatives, while the fluorescence quantum yield decreases from ∼30 to ∼7% for FL and AAs, respectively, making the triplet excited state lifetime and the singlet oxygen quantum yield of AAs at least comparable to those of FL and RFTA. We examined the performance of these heave-atom-free chromophores in the photooxidation of sulfides to afford sulfoxides. In accordance with the prolonged triplet excited state lifetime and enhanced triplet quantum yield, 2-5-fold performance enhancements were observed for AAs in the photooxidation of sulfides with respect to FL. We proposed that the key reactive oxygen species of AA-sensitized photooxidation are singlet oxygen and superoxide radical anion based on mechanistic investigations. The research highlights the superior performance of AAs in photocatalysis and would be helpful to rationalize the design of efficient heavy-atom-free organic photocatalysts.

| S-EPMC7227068 | biostudies-literature

Developing efficient heavy-atom-free photosensitizers applicable to TTA upconversion in polymer films.

Project description:Heavy-atom-free triplet photosensitizers are developed by harnessing the thermally active triplet state of carbazolyl dicyanobenzene (CDCB) derivatives and applied to realize visible-to-ultraviolet photon upconversion (UC) via triplet-triplet annihilation (TTA). Demonstrating an annihilator-appending strategy, the designed sensitizers effectively realize TTA UC in polyurethane films with 2,7-di-tert-butylpyrene (DBP) as the annihilator/emitter. The covalently tethered DBP to CDCB is proven critical for achieving the superior sensitizing and UC performance in the solid matrix, essentially by suppressing the reverse ISC and more effectively transferring triplet excitons to free emitters.

| S-EPMC5975838 | biostudies-literature

Metallopolymer strategy to explore hypoxic active narrow-bandgap photosensitizers for effective cancer photodynamic therapy.

Project description:Practical photodynamic therapy calls for high-performance, less O2-dependent, long-wavelength-light-activated photosensitizers to suit the hypoxic tumor microenvironment. Iridium-based photosensitizers exhibit excellent photocatalytic performance, but the in vivo applications are hindered by conventional O2-dependent Type-II photochemistry and poor absorption. Here we show a general metallopolymerization strategy for engineering iridium complexes exhibiting Type-I photochemistry and enhancing absorption intensity in the blue to near-infrared region. Reactive oxygen species generation of metallopolymer Ir-P1, where the iridium atom is covalently coupled to the polymer backbone, is over 80 times higher than that of its mother polymer without iridium under 680 nm irradiation. This strategy also works effectively when the iridium atom is directly included (Ir-P2) in the polymer backbones, exhibiting wide generality. The metallopolymer nanoparticles exhibiting efficient O2•- generation are conjugated with integrin αvβ3 binding cRGD to achieve targeted photodynamic therapy.

| S-EPMC10762066 | biostudies-literature

New photosensitizers for photodynamic therapy.

Project description:Photodynamic therapy (PDT) was discovered more than 100 years ago, and has since become a well-studied therapy for cancer and various non-malignant diseases including infections. PDT uses photosensitizers (PSs, non-toxic dyes) that are activated by absorption of visible light to initially form the excited singlet state, followed by transition to the long-lived excited triplet state. This triplet state can undergo photochemical reactions in the presence of oxygen to form reactive oxygen species (including singlet oxygen) that can destroy cancer cells, pathogenic microbes and unwanted tissue. The dual-specificity of PDT relies on accumulation of the PS in diseased tissue and also on localized light delivery. Tetrapyrrole structures such as porphyrins, chlorins, bacteriochlorins and phthalocyanines with appropriate functionalization have been widely investigated in PDT, and several compounds have received clinical approval. Other molecular structures including the synthetic dyes classes as phenothiazinium, squaraine and BODIPY (boron-dipyrromethene), transition metal complexes, and natural products such as hypericin, riboflavin and curcumin have been investigated. Targeted PDT uses PSs conjugated to antibodies, peptides, proteins and other ligands with specific cellular receptors. Nanotechnology has made a significant contribution to PDT, giving rise to approaches such as nanoparticle delivery, fullerene-based PSs, titania photocatalysis, and the use of upconverting nanoparticles to increase light penetration into tissue. Future directions include photochemical internalization, genetically encoded protein PSs, theranostics, two-photon absorption PDT, and sonodynamic therapy using ultrasound.

| S-EPMC4811612 | biostudies-literature

Near-Infrared Light-Triggered Photodynamic Therapy and Apoptosis Using Upconversion Nanoparticles With Dual Photosensitizers.

Project description:Elucidation of upconversion nanoparticles (UCNPs) that can be excited by near-infrared (NIR) light is an interesting topic in the field of photodynamic therapy (PDT). However, the PDT efficiency of conventional UCNPs is limited due to the low quantum yield and overheating effect of the 980 nm light source. In this study, a light source with a wavelength of 808 nm was used as an excitation source for Nd-doped UCNPs to solve the overheating effect. UCNPs with a core@shell structure (NaYF4:Yb,Er,Nd@NaYF4:Yb,Nd) were synthesized to increase the upconversion emission efficiency. Dual-color emitting Er-doped UCNPs and dual photosensitizers (Chlorin e6 and Rose Bengal) were used for enhanced PDT. Each photosensitizer could absorb red and green emissions of the UCNPs to generate reactive oxygen species (ROS), respectively. The ROS generation in a dual photosensitizer system is significantly higher than that in a single photosensitizer system. Additionally, PDT induces immunogenic apoptosis. In this study, by utilizing a highly efficient PDT agent, PDT-induced apoptosis was studied by biomarker analysis.

| S-EPMC7179334 | biostudies-literature

Dual Functioning Thieno-Pyrrole Fused BODIPY Dyes for NIR Optical Imaging and Photodynamic Therapy: Singlet Oxygen Generation without Heavy Halogen Atom Assistance.

Project description:We discovered a rare phenomenon wherein a thieno-pyrrole fused BODIPY dye (SBDPiR690) generates singlet oxygen without heavy halogen atom substituents. SBDPiR690 generates both singlet oxygen and fluorescence. To our knowledge, this is the first example of such a finding. To establish a structure-photophysical property relationship, we prepared SBDPiR analogs with electron-withdrawing groups at the para-position of the phenyl groups. The electron-withdrawing groups increased the HOMO-LUMO energy gap and singlet oxygen generation. Among the analogs, SBDPiR688, a CF3 analog, had an excellent dual functionality of brightness (82290 m(-1) cm(-1) ) and phototoxic power (99170 m(-1) cm(-1) ) comparable to those of Pc 4, due to a high extinction coefficient (211 000 m(-1) cm(-1) ) and balanced decay (Φflu =0.39 and ΦΔ =0.47). The dual functionality of the lead compound SBDPiR690 was successfully applied to preclinical optical imaging and for PDT to effectively control a subcutaneous tumor.

| S-EPMC7297209 | biostudies-literature

Heavy-Atom Free spiro Organoboron Complexes As Triplet Excited States Photosensitizers for Singlet Oxygen Activation.

Project description:Herein, we present a new strategy for the development of efficient heavy-atom free singlet oxygen photosensitizers based on rigid borafluorene scaffolds. Physicochemical properties of borafluorene complexes can be easily tuned through the choice of ligand, thus allowing exploration of numerous organoboron structures as potent 1O2 sensitizers. The singlet oxygen generation quantum yields of studied complexes vary in the range of 0.55-0.78. Theoretical calculations reveal that the introduction of the borafluorene moiety is crucial for the stabilization of a singlet charge transfer state, while intersystem crossing to a local triplet state is facilitated by orthogonal donor-acceptor molecular architecture. Our study shows that quantitative oxidation of selected organic substrates can be achieved in 20-120 min of irradiation with only 0.05 mol % loading of a photocatalyst.

| S-EPMC8453631 | 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