A basic understanding of how imaging nanoparticles are removed from the normal organs/tissues but retained in the tumors is important for their future clinical applications in early cancer diagnosis ...and therapy. In this review, we discuss current understandings of clearance pathways and tumor targeting of small-molecule- and inorganic-nanoparticle-based imaging probes with an emphasis on molecular nanoprobes, a class of inorganic nanoprobes that can escape reticuloendothelial system (RES) uptake and be rapidly eliminated from the normal tissues/organs via kidneys but can still passively target the tumor with high efficiency through the enhanced permeability permeability and retention (EPR) effect. The impact of nanoparticle design (size, shape, and surface chemistry) on their excretion, pharmacokinetics, and passive tumor targeting were quantitatively discussed. Synergetic integration of effective renal clearance and EPR effect offers a promising pathway to design low-toxicity and high-contrast-enhancement imaging nanoparticles that could meet with the clinical translational requirements of regulatory agencies.
With more and more engineered nanoparticles (NPs) being translated to the clinic, the United States Food and Drug Administration (FDA) has recently issued the latest draft guidance on ...nanomaterial‐containing drug products with an emphasis on understanding their in vivo transport and nano–bio interactions. Following these guidelines, NPs can be designed to target and treat diseases more efficiently than small molecules, have minimum accumulation in normal tissues, and induce minimum toxicity. In this Minireview, we integrate this guidance with our ten‐year studies on developing renal clearable luminescent gold NPs. These gold NPs resist serum protein adsorption, escape liver uptake, target cancerous tissues, and report kidney dysfunction at early stages. At the same time, off‐target gold NPs can be eliminated by the kidneys with minimum accumulation in the body. Additionally, we identify challenges to the translation of renal clearable gold NPs from the bench to the clinic.
NPs get clearance: Animal studies of renal clearable gold nanoparticles from the Zheng group in the past decade are revisited from the viewpoint of in vivo transport of nanoparticles and nano–bio interactions in tissues/organs. Additionally, these results are integrated with the latest FDA guidance on nanomedicines.
Kidneys are a major organ for blood filtration and waste elimination and thus play a key role in the transport and clearance of nanoparticles in vivo. The interactions of nanoparticles with different ...kidney compartments can be precisely regulated by modulating their size, shape and surface chemistry. The quantitative understanding of nanoparticle–kidney interactions at the molecular level is important for improving disease targeting, precisely controlling nanoparticle transport and clearance, and minimizing the potential health hazards of nanomedicines. In this Review, we summarize the glomerular filtration of macromolecules and nanoparticles in the kidney and survey kidney imaging techniques for the study of nanoparticle–kidney interactions ex vivo and in vivo. We investigate the different transport mechanisms of nanoparticles in the kidneys and discuss size, charge and shape dependencies in renal clearance. Nanoparticles are then investigated for the preclinical and clinical detection and treatment of diseases such as kidney dysfunction and cancer. Finally, challenges and opportunities for renal-clearable nanoparticles are highlighted.
The glomerular filtration barrier is known as a 'size cutoff' slit, which retains nanoparticles or proteins larger than 6-8 nm in the body and rapidly excretes smaller ones through the kidneys. ...However, in the sub-nanometre size regime, we have found that this barrier behaves as an atomically precise 'bandpass' filter to significantly slow down renal clearance of few-atom gold nanoclusters (AuNCs) with the same surface ligands but different sizes (Au
, Au
and Au
). Compared to Au
(∼1.0 nm), just few-atom decreases in size result in four- to ninefold reductions in renal clearance efficiency in the early elimination stage, because the smaller AuNCs are more readily trapped by the glomerular glycocalyx than larger ones. This unique in vivo nano-bio interaction in the sub-nanometre regime also slows down the extravasation of sub-nanometre AuNCs from normal blood vessels and enhances their passive targeting to cancerous tissues through an enhanced permeability and retention effect. This discovery highlights the size precision in the body's response to nanoparticles and opens a new pathway to develop nanomedicines for many diseases associated with glycocalyx dysfunction.
While inorganic nanoparticles (NPs) with tunable and diverse material properties open up unprecedented opportunities for novel biomedical technologies, translating these NPs into clinical practices ...has been severely hampered by the toxicity induced by their nonspecific accumulation in healthy tissues/organs. In the past few years, the emergence of renal clearable inorganic NPs has made it possible to address this long-term challenge. This review summarizes size, shape, surface chemistry and biodegradation considerations in the design of renal clearable inorganic NPs and their strengths over conventional non-renal clearable NPs and small-molecule contrast agents in tumor targeting. Finally, some materials chemistry challenges in the development of renal clearable inorganic NPs and their biomedical implications beyond tumor targeting are discussed.
Elevated anthropogenic acid deposition has accelerated forest soil acidification in southern China. However, the observed responses to increased acid inputs are quite variable among different forest ...soils, and the reasons remain unclear. To study the causes for the different responses, soil columns taken from a young pine forest (PF) and an old evergreen broadleaved forest (BF) were applied three levels of acid addition treatments for 60 days. We found that the PF soils were quite acid-sensitive, and the high acid treatment significantly decreased soil pH at 0–20 cm soil layer while significantly increased exchangeable H+ at both 0–20 and 20–40 cm soil layers. Both the low and high acid treatments significantly increased exchangeable Na+ at 0–20 cm soil layer and Ca2+ and Mg2+ at 20–40 cm soil layer. Furthermore, the high acid treatment also significantly increased leaching losses of H+, Ca2+, Mg2+ and Al3+. In contrast, the BF soils were able to buffer both the low and high acid treatments without significantly decreasing soil pH and increasing major exchangeable cations including Al3+ and their leaching losses. The significant differences in soil organic matter content were found to be responsible for these different responses, as a result of significantly positive correlation between cation exchange capacity (CEC) and organic carbon in both forest soils. The BF soils had higher organic matter than the PF soils, therefore a greater CEC for consuming H+ and a stronger capacity for binding cations. Our results explained why the PF soil pH decreased from 4.3 to 3.8, while the BF soil pH did not change significantly over the last 16 years, and highlighted the important roles of soil organic matter in acid buffering and retaining of major cations, especially for Al3+ in the very acidic forest soils in southern China.
•Aluminum dominates acid buffering processes in pine and broadleaved forest soils (pH < 4.2) in southern China.•Acid treatments decrease soil pH and increase leaching losses of metal cations from pine forest soil.•Broadleaved forest soil has a stronger acid buffering capacity because of its higher organic matter content.•Soil organic matter is a major contributor to cation exchange capacity and adsorption of Al3+ in acidic forest soil.
Glutathione-coated luminescent gold nanoparticles (GS-AuNPs) with diameters of ∼2.5 nm behave like small dye molecules (IRDye 800CW) in physiological stability and renal clearance but exhibit a much ...longer tumor retention time and faster normal tissue clearance, indicating that the well-known enhanced permeability and retention effect, a unique strength of conventional NPs in tumor targeting, still exists in such small NPs. These merits enable the AuNPs to detect tumor more rapidly than the dye molecules without severe accumulation in reticuloendothelial system organs, making them very promising for cancer diagnosis and therapy.
Got it PEGged: PEGylation and zwitterionization have distinct effects on the pharmacokinetic and tumor‐targeting properties of luminescent gold nanoparticles (AuNPs), although both strategies lead to ...effective renal clearance. High tumor‐targeting efficiency and specificity were obtained with PEGylated AuNPs, whereas rapid tumor detection was more readily achieved with zwitterionic AuNPs. HD=hydrodynamic diameter, GS=glutathione.
The flow behavior of polydisperse particles in rolling mode rotating drum is important in industry, but it is still not clear. In this work, the discrete element method (DEM) is used to explore the ...flow of particles in the three-dimensional drum. After the accuracy of simulation verified by the experimental data from literature, the particle bed is divided into active layer and passive layer. The flow behavior of polydisperse particles was revealed by studying the particle velocity, residence time, mixing and axial dispersion in different regions in the drum. By exploring the parameters such as rotation speed, filling level and the shape and position of the lifter, some ideas are provided for improving the performance of the rolling mode rotating drum. In addition, the difference of flow behavior between polydisperse particles and monodisperse particles is also given, which can provide some reference for the industrial application of complex particle system.
Flow behavior of polydispersed particles in active and passive layers and the parameter optimization of rotating drum. Display omitted
•DEM is used to study the flow behavior of polydisperse particles in a rolling mode rotating drum.•Velocity, residence time, mixing and axial dispersion of active and passive layers are studied.•Improvement scheme of filling level, rotation speed and lifter of rotating drum is given.•Reference is provided for application of monodisperse particle theory to polydisperse particles.
Up-converting rare-earth nanophosphors (UCNPs) have great potential to revolutionize biological luminescent labels, but their use has been limited by difficulties in obtaining UCNPs that are ...biocompatible. To address this problem, we have developed a simple and versatile strategy for converting hydrophobic UCNPs into water-soluble and carboxylic acid-functionalized analogues by directly oxidizing oleic acid ligands with the Lemieux-von Rudloff reagent. This oxidation process has no obvious adverse effects on the morphologies, phases, compositions and luminescent capabilities of UCNPs. Furthermore, as revealed by Fourier transform infrared (FTIR) and NMR results, oleic acid ligands on the surface of UCNPs can be oxidized into azelaic acids (HOOC(CH2)7COOH), which results in the generation of free carboxylic acid groups on the surface. The presence of free carboxylic acid groups not only confers high solubility in water, but also allows further conjugation with biomolecules such as streptavidin. A highly sensitive DNA sensor based on such streptavidin-coupled UCNPs have been prepared, and the demonstrated results suggest that these biocompatible UCNPs have great superiority as luminescent labeling materials for biological applications.
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