Renal clearable nanoparticles have been drawing much attention as they can avoid prolonged accumulation in the body by efficiently clearing through the kidneys. While much effort has been made to understand their interactions within the kidneys, it remains unclear whether their transport could be influenced by other organs, such as the liver, which plays a crucial role in metabolizing and eliminating both endogenous and exogenous substances through various biotransformation processes. Here, by utilizing renal clearable IRDye800CW conjugated gold nanocluster (800CW-GS-Au) as a model, we found that although 800CW-GS-Au strongly resisted serum-protein binding and exhibited minimal accumulation in the liver, its surface was still gradually modified by hepatic glutathione-mediated biotransformation when passing through the liver, resulting in the dissociation of IRDye800CW from Au and biotransformation-generated fingerprint message of 800CW-GS-Au in urine, which allowed us to facilely quantify its urinary biotransformation index (UBI) via urine chromatography analysis. Moreover, we observed the linear correlation between UBI and hepatic glutathione concentration, offering us a noninvasive method for quantitative detection of liver glutathione level through a simple urine test. Our discoveries would broaden the fundamental understanding of in vivo transport of nanoparticles and advance the development of urinary probes for noninvasive biodetection.
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http://dx.doi.org/10.1002/anie.202409477 | DOI Listing |
Trends Biotechnol
December 2024
Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, València, Spain; Departamento de Química, Universitat Politècnica de València, Camino de Vera s/n 46022, Valencia, Spain; CIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III, 28029, Madrid, Spain; Unidad Mixta UPV-CIPF de Investigación en Mecanismos de Enfermedades y Nanomedicina, Valencia, Universitat Politècnica de València, Centro de Investigación Príncipe Felipe, Avenida Eduardo Primo Yúfera, 3, 46012, Valencia, Spain; Unidad Mixta de Investigación en Nanomedicina y Sensores, Universitat Politècnica de València, Instituto de Investigación Sanitaria La Fe (IISLAFE), Avenida Fernando Abril Martorell, 106, 46026, Valencia, Spain.
The demand for novel, minimally invasive, cost-effective, and easily readable diagnostic tools, primarily designed for the longitudinal monitoring of diseases and their treatments, has promoted the development of diagnostic systems that selectively target cells, tissues, or organs, at the same time minimizing their nonspecific accumulation, thus reducing the risk of toxicity and side effects. In this review, we explore the development of renal-clearable systems in non-invasive or minimally invasive detection protocols, all with the objective of minimizing nonspecific accumulation and its associated toxicity effects through quick renal excretion. These probes can identify molecules of interest or different healthy states of the patients through the direct analysis of urine (urinalysis).
View Article and Find Full Text PDFAdv Mater
December 2024
State Key Laboratory of Food Science and Technology, International Joint Research Laboratory for Biointerface and Biodetection, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, China.
In this study, polypeptide TGGGPLGVARGKGGC-induced chiral manganese dioxide supraparticles (MnO SPs) are prepared for sensitive quantification of matrix metalloproteinase-9 (MMP-9) in vitro and in vivo. The results show that L-type manganese dioxide supraparticles (L-MnO SPs) exhibited twice the affinity for the cancer cell membrane receptor CD47 (cluster of differentiation, integrin-associated protein) than D-type manganese dioxide supraparticles (D-MnO SPs) to accumulate at the tumor site after surface modification of the internalizing arginine-glycine-aspartic acid (iRGD) ligand, specifically reacting with the MMP-9, disassembling into ultrasmall nanoparticles (NPs), and efficiently underwent renal clearance. Furthermore, L-MnO facilitates the quantification of MMP-9 in mouse tumor xenografts, as demonstrated by circular dichroism (CD) and magnetic resonance imaging (MRI) within 2 h.
View Article and Find Full Text PDFNat Commun
November 2024
Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.
Staphylococcus aureus is a leading cause of nosocomial implant-associated infections, causing significant morbidity and mortality, underscoring the need for rapid, non-invasive, and cost-effective diagnostics. Here, we optimise the synthesis of renal-clearable gold nanoclusters (AuNCs) for enhanced catalytic activity with the aim of developing a sensitive colourimetric diagnostic for bacterial infection. All-atom molecular dynamics (MD) simulations confirm the stability of glutathione-coated AuNCs and surface access for peroxidase-like activity in complex physiological environments.
View Article and Find Full Text PDFAnal Chem
December 2024
College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.
Hepatic ischemia-reperfusion injury (HIRI) and induced systemic inflammation is a time-dependent multistage process which poses a risk of causing direct hepatic dysfunction and multiorgan failure. Real-time in situ comprehensive visualization assessment is important and scarce for imaging-guided therapeutic interventions and timely efficacy evaluation. Here, a logically activatable nanoreporter (termed QD@IR783-TK-FITC) is developed for time-phase imaging quantification of HIRI and induced systemic inflammation.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
October 2024
Department of Chemistry and Biochemistry, The University of Texas at Dallas 800 W. Campbell Rd., Richardson, TX 75080, USA.
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