Jing Chen,Yunjing Gao,Qin Ma,Xiaoyan Hu,Yali Xu,Xiaoquan Lu
In the present work, the classical synthesis method of 5,10,15,20-(4-sulphonatophenyl) porphyrin (TPPS 4 ) was improved. The synthesis process became more environmentally friendly, and the yield was increased by 10%. We constructed a sensitive fluorescent sensor for detection hydrogen peroxide (H 2 O 2 ) and glucose (C 6 H 12 O 6 ) by using the hyperfluorescence of TPPS 4 . The TPPS 4 -Fe 3+ complex system of the sensor could generate electron transfer process (ET) in the process of hydrogen peroxide (H 2 O 2 ) and glucose oxidation, which quenched the TPPS 4 fluorescence. The system had a linear range of 0–42 μM for hydrogen peroxide, and the minimum detectable limit (LOD) was 1.24 nM (S/N = 3). Compared with other detection methods, the proposed method had the advantages of higher sensitivity, lower detection limit and more simple operation.
Jing Chen,Qin Ma,Xiaoyan Hu,Yunjing Gao,Xiaoyu Yan,Dongdong Qin,Xiaoquan Lu
In the present work, we proposed a novel naked-eye and turn-on fluorescence sensor based on the 5,10,15,20-(4-sulphonatophenyl) porphyrin (TPPS 4 )-Hg 2+ system with short assay time and high sensitivity to detect glutathione (GSH) in real samples. The TPPS 4 was the first time to detect GSH because of its high fluorescence quantum yield. The initial fluorescence from TPPS 4 was quenched by Hg 2+ with an electron transfer process. However, when put a certain concentration of GSH into this system, the fluorescence sensor was turned to the “on” state, which was related to a competitive affinity of Hg 2+ to GSH and the N atoms of porphyrin ring. Under the optimal conditions, the naked-eye detection limit was 0.43 nM and the limit of detection (LOD) was arrived to 16 fM (S/N = 3) for GSH. The linear regions are obtained by two ranges varying from 0 to 28.5 μM and from 38.15 to 61.87 μM. Furthermore, it was confirmed that the TPPS 4 -Hg 2+ fluorescence probe has excellent selectivity, high sensitivity and quick fluorescence response for GSH.
Can Wu,Qishu Jiao,Chunlu Wang,Yaxin Zheng,Xiaohui Pan,Wenying Zhong,Keming Xu
The use of lonidamine (LND) in photodynamic therapy (PDT) provides a viable approach to develop low-dose PDT modules with high efficacy, for LND potentiates cytotoxicity of photosensitizers through dysregulation of mitochondrial function. Yet, the efficacy of LND is restricted by its low accumulation in cancer cells, especially in the mitochondrial compartments. To address the problem, we design an LND-derived self-assembling peptide molecule (LND-K) that dually targets integrin receptors and mitochondria of cancer cells. The targeted cellular delivery of LND-K gives higher efficacy in ablation of mitochondrial function in melanoma cells A375, as compared to free LND or the control molecule that lacks mitochondria-targeting moieties. To integrate LND-K in a typical PDT module, we develop a nanofibrillar hydrogel system through co-assembly of LND-K and TPPS 4 , an anionic photosensitizer that forms tight electrostatic interactions with cationic residues of LND-K. Notably, hydrogel formulation of LND-K/TPPS 4 facilitates slow release of TPPS 4 over 14 days in vitro , and displays a longer retention time than aqueous solution of TPPS 4 in vivo . By integrating a mitochondria-targeted molecule (LND-K) in a typical PDT module, we achieve synergistic killing of A375 cells with dual drugs, where LND-K not only serves as a chemotherapeutic drug, but also potentiates the cytotoxicities of TPPS 4 toward A375 cells in vitro and in vivo . The peptide-based drug self-delivery system promises the development of efficacious combination treatments against cancer, that integrate cell sensitization with existing anticancer modules ( e.g. , chemotherapy and PDT) for enhanced therapeutic efficacy. Statement of significance This study reports the design and synthesis of a lonidamine (LND)-derived self-assembling peptide (LND-K) that dually targets integrin receptors and mitochondria of cancer cells. Under the precision guidance of a mitochondria-targeting sequence, LND-K-containing nanofibers target mitochondria and ablate mitochondrial functions. On one hand, the targeted delivery of LND-K reduces cell viabilities through a chemotherapy route; on the other hand, LND-K sensitizes cancer cells for subsequent PDT treatment with enhanced efficacy, which is mediated by induction of ROS, loss of mitochondrial membrane potential , and decrease of cellular ATP level. We believe that the design of mitochondria-targeted drug delivery systems with a self-assembling molecule provides a new approach to potentiate cytotoxicity of photosensitizers in a low-dose PDT module.
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