Acute wound injury is a common type of sports injury, and its local pathological changes are mainly traumatic inflammation, cell proliferation and tissue repair process, microvascular contraction often occurs briefly, vascular permeability increases, and water, electrolyte and plasma protein penetrate into the tissue space. Low-dose PDT (photodynamic therapy) promotes wound healing by promoting fibroblast migration, inducing instantaneous in-situ reactive oxygen species, promoting epidermal stem cell proliferation and migration, promoting dermal granulation tissue formation and angiogenesis, and regulating inflammatory processes. The CAR peptide, previously identified, was utilized as an adhesion molecule to facilitate the formation of tight junctions (TJ) and regulate intercellular adhesion among adjacent epithelial cells. Additionally, it was incorporated into the photosensitizer 5-ALA, presenting a novel antibacterial repair strategy for sports injuries.
Integrin α5β1 is a widely-recognized target for molecular probes in various pathological conditions, especially cancer. The development of computer screening approaches to identify novel high affinity ligands to tumor markers has paved the way for a new generation of tumor identification technology. In this study, we have developed an efficient pharmacophore-based computational strategy to screen two novel peptides, RYr and H5, with high affinity to integrin α5β1. Noninvasive optical imaging data showed that these two peptides could be specifically uptaken by α5β1 overexpressed-tumor cells in vitro and in vivo. And these peptides-based probes could retain in tumor tissue for precise tumor identification. Results indicated that the newly identified peptides with high affinity to integrin α5β1 can be used for precise tumor identification and treatment. And this work exploited more functionalities of pharmacophore-based computational strategy for screening targeting-peptides.
KEYWORDS: In vivo imaging, Liver, Target detection, In vitro testing, Tissues, Confocal microscopy, Luminescence, Tumors, Near infrared, Statistical analysis
Hepatocellular carcinoma (HCC) has been the third most common cause of cancer-related death worldwide. Glypican-3 (GPC3) is a heparin sulfate proteoglycan linked to the cell membrane by a glycosyl-phosphatidylinositol anchor (GPI) and is expressed by 75% of all hepatocellular carcinomas but undetectable in healthy liver tissue or liver with focal lesions. What’s more, GPC3 has been gradually applied in clinical applications as a specific indicator for the early detection and prognosis of HCC. As GPC3 can also regulate many pathways in HCC pathogenesis including Wnt, Hh and Yap signaling, it has been shown that GPC3 knockdown can inhibit HCC growth, reinforcing the important roles of GPC3 in HCC development. For HCC early detection, we designed a peptide targeting GPC3 that allows to establish a fluorescent dyes-labeled probe. Firstly, according to the structure of the GPC3 antibody GC33 and the positive peptide reported in the literature, we generated a peptide consisting of twelve amino acids named 12P that may bind to GPC3 with tight binding ability and specificity. In vitro testing, we utilized FCM and laser confocal microscopy to verify its specificity of targeting to the high expression cells of GPC3. What’s more, we linked 12P with a near infrared dye to verify its in vivo targeting ability. All results indicated that 12P possessed potent binding capacity which could be used as a targeting module in GPC3 detection probe.
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