Matrix metalloproteinase 2 (MMP-2) in metastatic cancer tissue, which is associated with a poor prognosis, is a potential target for tumor imaging in vivo. Here, we describe a metastatic cancer cell-targeted protein nanocage. An MMP-2-binding peptide, termed CTT peptide (CTTHWGFTLC), was conjugated to the surface of a naturally occurring heat shock protein nanocage by genetic modification. The engineered protein nanocages showed a binding affinity for MMP-2 and selective uptake in cancer cells that highly expressed MMP-2 in vitro. In near-infrared fluorescence imaging, the nanocages showed specific and significant accumulation in tumor tissue after intravenous injection in vivo. These protein nanocages conjugated with CTT peptide could be potentially applied to a noninvasive near-infrared fluorescence detection method for imaging gelatinase activity in metastatic tumors in vivo.
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http://dx.doi.org/10.3390/ijms16010148 | DOI Listing |
Talanta
December 2024
Marshall Laboratory of Biomedical Engineering, Shenzhen Key Laboratory for Nano-Biosensing Technology, Department of Biomedical Engineering, Medical School, Shenzhen University, Shenzhen, Guangdong, 518060, PR China. Electronic address:
Colorimetric enzyme-linked immunosorbent assays (CELISAs) have long been used for protein biomarker detection in diagnostics. Unfortunately, as confined by the monochromatic nature of detection signals and the limited catalytic activity of enzymes, CELISAs suffer from poor visual resolution and low sensitivity, hindering their effectiveness for early diagnostics in resource-limited settings. Herein, we report an ultrasensitive, high-visual-resolution CELISA (named PE-TSA-AuAg Cage-CELISA) that combines kinetically controlled growth of Ag in AuAg nanocages with poly-enzyme-boosted tyramide signal amplification (PE-TSA), enabling visual semiquantitative detection of protein biomarkers at attomolar levels with the naked eye.
View Article and Find Full Text PDFNature
December 2024
Institute for Protein Design, University of Washington, Seattle, WA, USA.
Discrete protein assemblies ranging from hundreds of kilodaltons to hundreds of megadaltons in size are a ubiquitous feature of biological systems and perform highly specialized functions. Despite remarkable recent progress in accurately designing new self-assembling proteins, the size and complexity of these assemblies has been limited by a reliance on strict symmetry. Here, inspired by the pseudosymmetry observed in bacterial microcompartments and viral capsids, we developed a hierarchical computational method for designing large pseudosymmetric self-assembling protein nanomaterials.
View Article and Find Full Text PDFNature
December 2024
Department of Biochemistry, University of Washington, Seattle, WA, USA.
Four, eight or twenty C3 symmetric protein trimers can be arranged with tetrahedral, octahedral or icosahedral point group symmetry to generate closed cage-like structures. Viruses access more complex higher triangulation number icosahedral architectures by breaking perfect point group symmetry, but nature appears not to have explored similar symmetry breaking for tetrahedral or octahedral symmetries. Here we describe a general design strategy for building higher triangulation number architectures starting from regular polyhedra through pseudosymmetrization of trimeric building blocks.
View Article and Find Full Text PDFRegen Biomater
October 2024
State Key Laboratory of Refractories and Metallurgy, Key Laboratory of Coal Conversion & New Carbon Materials of Hubei Province, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, P.R. China.
Acta Pharm Sin B
November 2024
Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
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