RESUMO
RNA is an emerging drug target that opens new perspectives in the treatment of viral and bacterial infections, cancer and a range of so far incurable genetic diseases. Among the various strategies towards the design and development of selective and efficient ligands for targeting and detection of therapeutically relevant RNA, photoswitchable RNA binders represent a very promising approach due to the possibility to control the ligand-RNA and protein-RNA interactions by light with high spatiotemporal resolution. However, the field of photoswitchable RNA binders still remains underexplored due to challenging design of lead structures that should combine high RNA binding selectivity with efficient photochemical performance. The aim of this highlight article is to describe the development of photoswitchable noncovalent RNA binders and to outline the current situation and perspectives of this emerging interdisciplinary field.
Assuntos
Compostos Azo/metabolismo , Compostos de Benzilideno/metabolismo , RNA/metabolismo , Compostos Azo/química , Compostos Azo/efeitos da radiação , Compostos de Benzilideno/química , Compostos de Benzilideno/efeitos da radiação , HIV/química , Humanos , Ligantes , Luz , EstereoisomerismoRESUMO
Biodegradable nanostructures displaying aggregation-induced emission (AIE) are desirable from a biomedical point of view, due to the advantageous features of loading capacity, emission brightness, and fluorescence stability. Herein, biodegradable polymers comprising poly (ethylene glycol)-block-poly(caprolactone-gradient-trimethylene carbonate) (PEG-P(CLgTMC)), with tetraphenylethylene pyridinium-TMC (PAIE) side chains have been developed, which self-assembled into well-defined polymersomes. The resultant AIEgenic polymersomes are intrinsically fluorescent delivery vehicles. The presence of the pyridinium moiety endows the polymersomes with mitochondrial targeting ability, which improves the efficiency of co-encapsulated photosensitizers and improves therapeutic index against cancer cells both in vitro and in vivo. This contribution showcases the ability to engineer AIEgenic polymersomes with structure inherent fluorescence and targeting capacity for enhanced photodynamic therapy.
Assuntos
Antineoplásicos/farmacologia , Plásticos Biodegradáveis/farmacologia , Corantes Fluorescentes/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Poliésteres/farmacologia , Polietilenoglicóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Compostos de Benzilideno/síntese química , Compostos de Benzilideno/farmacologia , Compostos de Benzilideno/efeitos da radiação , Plásticos Biodegradáveis/síntese química , Plásticos Biodegradáveis/efeitos da radiação , Compostos de Boro/síntese química , Compostos de Boro/farmacologia , Compostos de Boro/efeitos da radiação , Linhagem Celular Tumoral , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Humanos , Luz , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Poliésteres/síntese química , Poliésteres/efeitos da radiação , Polietilenoglicóis/síntese química , Polietilenoglicóis/efeitos da radiação , Compostos de Piridínio/síntese química , Compostos de Piridínio/farmacologia , Compostos de Piridínio/efeitos da radiaçãoRESUMO
Supramolecular coordination is an efficient strategy to construct supramolecular coordination frameworks with predesigned structures, assembled shapes, and specific function. In this work, we report the synthesis, structural characterization, and photophysical property of two tetraphenylethene-based supramolecular coordination frameworks 1a and 1b formed from 1,1,2,2-tetrakis(4-(pyridin-4-yl)phenyl)ethene (2a) or 1,1,2,2-tetrakis(4-((E)-2-(pyridin-4-yl)vinyl)phenyl)ethene (2b) and a linear difunctional platinum(II) ligand (3a) via coordination-driven self-assembly. Controlled by the specific angularity and geometry of tetraphenylethene (with 60° and 120°) and difunctional Pt(II) linker (with 180°), these supramolecular coordination frameworks possess a well-defined and two-dimensional (2D) rhombic network-type topology with good periodicity and porosity. Given the aggregation-induced emission (AIE) property of tetraphenylethene units and the porosity of frameworks, 1a and 1b have been successfully used as fluorescent platforms and energy donors to fabricate efficient artificial light-harvesting materials with two fluorescent acceptors (Nile Red and Sulforhodamine 101) via noncovalent interactions in aqueous solution. Furthermore, these light-harvesting materials have been applied for promoting cancer cell imaging with a full shift of imaging channels from blue/green channels to the red channel. Thus, this study provides an effective approach to fabricate functional frameworks as fluorescent platforms for developing more fluorescent materials.
Assuntos
Compostos de Benzilideno/química , Complexos de Coordenação/química , Corantes Fluorescentes/química , Estruturas Metalorgânicas/química , Compostos de Benzilideno/efeitos da radiação , Complexos de Coordenação/efeitos da radiação , Células HeLa , Humanos , Ligantes , Luz , Estruturas Metalorgânicas/efeitos da radiação , Microscopia Confocal , Microscopia de Fluorescência , Neoplasias/diagnóstico por imagem , Oxazinas/química , Platina/química , Platina/efeitos da radiação , Rodaminas/químicaRESUMO
We present a near-infrared (NIR) fluorescent probe, NR-HNO, which was successfully applied to visualizing H2S/NO "crosstalk" by the fluorescence detection of nitroxyl with a fast response time (5 min) and a large Stokes shift (131 nm) in living cells and tissue; it was also used to image nitroxyl in live mice.
Assuntos
Compostos de Benzilideno/química , Corantes Fluorescentes/química , Sulfeto de Hidrogênio/metabolismo , Óxido Nítrico/metabolismo , Óxidos de Nitrogênio/análise , Animais , Compostos de Benzilideno/efeitos da radiação , Linhagem Celular Tumoral , Corantes Fluorescentes/efeitos da radiação , Humanos , Rim/metabolismo , Luz , Limite de Detecção , Fígado/metabolismo , Camundongos , Microscopia de Fluorescência/métodos , Nitritos/química , Óxidos de Nitrogênio/metabolismo , Espectrometria de Fluorescência/métodosRESUMO
Tumor-associated macrophages (TAMs) that exist in tumor microenvironment promote tumor progression and have been suggested as a promising therapeutic target for cancer therapy in preclinical studies. Development of theranostic systems capable of specific targeting, imaging, and ablation of TAMs will offer clinical benefits. Here we constructed a theranostic probe, namely, TPE-Man, by attaching mannose moieties to a red-emissive and AIE (aggregation-induced emission)-active photosensitizer. TPE-Man can specifically recognize a mannose receptor that is overexpressed on TAMs by the sugar-receptor interaction and enables fluorescent visualization of the mannose-receptor-positive TAMs in high contrast. The histologic study of mouse tumor sections further verifies TPE-Man's excellent targeting specificity being comparable with the commercial mannose-receptor antibody. TAMs can be effectively eradicated upon exposure to white light irradiation via a photodynamic therapy effect. To our knowledge, this is the first small molecular theranostic probe for TAMs that revealed combined advantages of low cost, high targeting specificity, fluorescent light-up imaging, and efficient photodynamic ablation.
Assuntos
Compostos de Benzilideno/farmacologia , Macrófagos/efeitos dos fármacos , Manosídeos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Animais , Compostos de Benzilideno/síntese química , Compostos de Benzilideno/efeitos da radiação , Compostos de Benzilideno/toxicidade , Manosídeos/síntese química , Manosídeos/efeitos da radiação , Manosídeos/toxicidade , Camundongos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidade , Ratos Sprague-Dawley , Nanomedicina Teranóstica/métodosRESUMO
Photodynamic therapy (PDT) involves a photosensitizing agent activated with light to induce cell death. Two-photon excited PDT (TPE-PDT) offers numerous benefits compared to traditional one-photon induced PDT, including an increased penetration depth and precision. However, the in vitro profiling and comparison of two-photon photosensitizers (PS) are still troublesome. Herein, we report the development of an in vitro screening platform of TPE-PS using a 3D osteosarcoma cell culture. The platform was tested using three different two-photon (2P) active compounds - a 2P sensitizer P2CK, a fluorescent dye Eosin Y, and a porphyrin derivative (TPP). Their 2P absorption cross-sections (σ2PA) were characterised using a fully automated z-scan setup. TPP exhibited a remarkably high σ2PA at 720 nm (8865 GM) and P2CK presented a high absorption at 850 nm (405 GM), while Eosin Y had the lowest 2P absorption at the studied wavelengths (<100 GM). The cellular uptake of PS visualized using confocal laser scanning microscopy showed that both TPP and P2CK were internalized by the cells, while Eosin Y stayed mainly in the surrounding media. The efficiency of the former two TPE-PS was quantified using the PrestoBlue metabolic assay, showing a significant reduction in cell viability after two-photon irradiation. The possibility of damage localization was demonstrated using a co-culture of adipose derived stem cells together with osteosarcoma spheroids showing no signs of damage to the surrounding healthy cells after TPE-PDT.
Assuntos
Antineoplásicos/farmacologia , Compostos de Benzilideno/farmacologia , Amarelo de Eosina-(YS)/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Antineoplásicos/efeitos da radiação , Antineoplásicos/toxicidade , Compostos de Benzilideno/efeitos da radiação , Compostos de Benzilideno/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Amarelo de Eosina-(YS)/efeitos da radiação , Amarelo de Eosina-(YS)/toxicidade , Humanos , Células-Tronco Mesenquimais , Osteossarcoma/tratamento farmacológico , Fótons , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidade , Porfirinas/efeitos da radiação , Porfirinas/toxicidadeRESUMO
We report a novel fluorescent probe HBN-TCF for the detection of SO2 derivatives. This probe exhibited near-infrared fluorescence emission with an excitation wavelength of 620 nm. After reacting with SO32-, the emission channel at 664 nm decreased, while the new strong emission channel at 482 nm increased (λex = 400 nm), with a large emission distance (Δλ = 182 nm) observed. This probe exhibited the rapid and selective detection of SO2 derivatives compared with other sulfur-containing species and featured a low detection limit (82 nM). This colorimetric and ratiometric fluorescent probe showed high selectivity and sensitivity for detecting SO2 derivatives. The probe was also successfully exploited for the fluorescence imaging of intracellular and exogenous SO2 derivatives in BEL-7402 cells.