RÉSUMÉ
Phototherapy has garnered significant attention in the past decade. Photothermal and photodynamic synergistic therapy combined with NIR fluorescence imaging has been one of the most attractive treatment options because of the deep tissue penetration, high selectivity and excellent therapeutic effect. Benefiting from the superb photometrics and ease of modification, perylene diimide (PDI) and its derivatives have been employed as sensing probes and therapeutic agents in the biological and biomedical research fields, and exhibiting excellent potential. Herein, we reported the development of a novel organic small-molecule phototherapeutic agent, PDI-TN. The absorption of PDI-TN extends into the NIR region, which provides feasibility for NIR phototherapy. PDI-TN overcomes the traditional Aggregation-Caused Quenching (ACQ) effect and exhibits typical characteristics of Aggregation-Induced Emission (AIE). Subsequently, PDI-TN NPs were obtained by using an amphiphilic triblock copolymer F127 to encapsulate PDI-TN. Interestingly, the PDI-TN NPs not only exhibit satisfactory photothermal effects, but also can generate O2â¢- and 1O2 through type I and type II pathways, respectively. Additionally, the PDI-TN NPs emit strong fluorescence in the NIR-II region, and show outstanding therapeutic potential for in vivo NIR-II fluorescence imaging. To our knowledge, PDI-TN is the first PDI derivative used for NIR-II fluorescence imaging-guided photodynamic and photothermal synergistic therapy, which suggests excellent potential for future biological/biomedical applications.
Sujet(s)
Imides , Imagerie optique , Pérylène , Photothérapie dynamique , Pérylène/analogues et dérivés , Pérylène/composition chimique , Pérylène/pharmacologie , Pérylène/usage thérapeutique , Imides/composition chimique , Imides/usage thérapeutique , Photothérapie dynamique/méthodes , Humains , Imagerie optique/méthodes , Animaux , Souris , Colorants fluorescents/composition chimique , Photosensibilisants/composition chimique , Photosensibilisants/usage thérapeutique , Photosensibilisants/pharmacologie , Nanoparticules/composition chimique , Nanoparticules/usage thérapeutique , Thérapie photothermique , Rayons infrarouges , Lignée cellulaire tumoraleRÉSUMÉ
Cysteine (Cys) is a significant biological mercaptan that achieves key roles in several important physiological processes, such as reversible redox homeostasis in living organisms. Abnormal levels of Cys in the human body are directly related to many diseases. In this work, we constructed a sensitive sensor (Cys-NR) by connecting a Cys recognition group to a Nile red derivative. Due to photo-induced electron transfer (PET), the Cys-NR probe showed little fluorescence at 650 nm. With the addition of Cys to the assay solution, the chlorine unit of the probe was substituted by the thiol group of Cys. Further, the amino and sulfhydryl groups in cysteine underwent an intramolecular rearrangement, which led to the Cys-NR probe water solution turning from colorless to pink with an enhancement in fluorescence. The red fluorescence at 650 nm increased about 20 times. Based on the turn-on signal, a selective Cys detection method is developed. The probe signal is not affected by various potential interferences or other competing biothiols and the limit of detection (LOD) is determined to be 0.44 µM. In addition, the probe is further employed for imaging of Cys in live cells, revealing good biological imaging ability that could provide a new way of intracellular Cys detection.
Sujet(s)
Cystéine , Colorants fluorescents , Humains , Thiols , Oxazines , Cellules HeLa , Spectrométrie de fluorescence , Glutathion , HomocystéineRÉSUMÉ
Hematopoietic stem cells (HSCs) and skeletal stem cells (SSCs) cohabit in the bone marrow. KITL (C-KIT ligand) from LEPR+ adult bone marrow stromal cells is pivotal for HSC maintenance. In contrast, it remains unclear whether KITL/C-KIT signaling also regulates SSCs. Here, we lineage traced C-KIT+ cells and found that C-KIT was expressed by fetal, but not postnatal skeletal progenitors. Fetal C-KIT+ cells gave rise to 20% of LEPR+ stromal cells in adult bone marrow, forming nearly half of all osteoblasts. Disruption of mTOR signaling in fetal C-KIT+ cells impaired bone formation. Notably, conditional deletion of Kitl from PRX1+ fetal bone marrow stromal cells, but not LEPR+ adult bone marrow stromal cells, significantly increased bone formation. Thus, our work identified C-KIT+ skeletal progenitors as an important source of bones formed during development.