Biphenyl Wrinkled Mesoporous Silica Nanoparticles for pH-Responsive Doxorubicin Drug Delivery.

Biphenyl wrinkled mesoporous silica nanoparticles with controlled particle size and high surface area were evaluated for the storage and delivery of doxorubicin. The average particle size and surface area were ~70 nm and ~1100 m/g. The doxorubicin loading efficiency was 38.

Enhancing ZnO nanowire gas sensors using Au/FeO hybrid nanoparticle decoration.

Heterojunctions are an important strategy for designing high performance electrical sensor materials and related devices. Herein, a new type of metal-semiconductor hybrid nanoparticle has been successfully used to remarkably sensitize the surface of ZnO nanowires for detecting NO with high responses over a broad temperature window ranging from room temperature to 600 °C. These hybrid nanoparticles are comprised of iron oxide nanowires with well dispersed single crystalline Au nanoparticles.

Renal clearable nanocarriers: Overcoming the physiological barriers for precise drug delivery and clearance.

Physiological barriers encountered in the clinical translation of cancer nanomedicines inspire the community to more deeply understand nano-bio interactions in not only tumor microenvironment but also entire body and develop new nanocarriers to tackle these barriers. Renal clearable nanocarriers are one kind of these newly emerged drug delivery systems (DDSs), which enable drugs to rapidly penetrate into the tumor cores with no need of long blood retention and escape macrophage uptake in the meantime they can also enhance body elimination of non-targeted anticancer drugs. As a result, they can improve therapeutic efficacies and reduce side effects of anticancer drugs.

In Situ Ligand-Directed Growth of Gold Nanoparticles in Biological Tissues.

Fundamental understandings and precise control of nanoparticle growth in the complex biological environment are crucial to broadening their potential applications in tissue imaging. Herein, we report that glutathione (GSH), a widely used capping ligand for precise control of the size of gold nanoparticle (AuNP) down to single-atom level in test tubes, can also be used to direct the selective growth of the AuNPs in the mitochondria of renal tubule cells as well as hippocampus cells in the tissues. Precise control of this growth process can lead to the formation of both ultrasmall AuNPs with near-infrared luminescence and large plasmonic AuNPs.

Publisher Correction: On the issue of transparency and reproducibility in nanomedicine.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Publisher Correction: On the issue of transparency and reproducibility in nanomedicine.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Correlating Anticancer Drug Delivery Efficiency with Vascular Permeability of Renal Clearable Versus Non-renal Clearable Nanocarriers.

Enhancing tumor targeting of nanocarriers has been a major strategy for advancing clinical translation of cancer nanomedicines. Herein, we report a head-to-head comparison between 5 nm renal clearable and 30 nm non-renal clearable gold nanoparticle (AuNP)-based drug delivery systems (DDSs) in the delivery of doxorubicin (DOX). While the two DDSs themselves had comparable tumor targeting, we found their different vascular permeability played an even more important role than blood retention in the delivery and intratumoral transport of DOX, of which tumor accumulation, efficacy, and therapeutic index were enhanced 2, 7, and 10-fold, respectively, for the 5 nm DDS over 30 nm one.

Tuning the In Vivo Transport of Anticancer Drugs Using Renal-Clearable Gold Nanoparticles.

Precise control of in vivo transport of anticancer drugs in normal and cancerous tissues with engineered nanoparticles is key to the future success of cancer nanomedicines in clinics. This requires a fundamental understanding of how engineered nanoparticles impact the targeting-clearance and permeation-retention paradoxes in the anticancer-drug delivery. Herein, we systematically investigated how renal-clearable gold nanoparticles (AuNPs) affect the permeation, distribution, and retention of the anticancer drug doxorubicin in both cancerous and normal tissues.

Control of occlusion of middle cerebral artery in perinatal and neonatal mice with magnetic force.

Ischemic perinatal stroke (IPS) is common, resulting in significant mortality and morbidity. In such cases, the incidence of unilateral arterial cerebral infarction is often occluded in the middle cerebral artery (MCA), leading to focal ischemia. In adult rodents, blockage of MCA is the most frequently used strategy for ischemic stroke study.

Physiological stability and renal clearance of ultrasmall zwitterionic gold nanoparticles: Ligand length matters.

Efficient renal clearance has been observed from ultrasmall zwitterionic glutathione-coated gold nanoparticles (GS-AuNPs), which have broad preclinical applications in cancer diagnosis and kidney functional imaging. However, origin of such efficient renal clearance is still not clear. Herein, we conducted head-to-head comparison on physiological stability and renal clearance of two zwitterionic luminescent AuNPs coated with cysteine and glycine-cysteine (Cys-AuNPs and Gly-Cys-AuNPs), respectively.

Dose Dependencies and Biocompatibility of Renal Clearable Gold Nanoparticles: From Mice to Non-human Primates.

While dose dependencies in pharmacokinetics and clearance are often observed in clinically used small molecules, very few studies have been dedicated to the understandings of potential dose-dependent in vivo transport of nanomedicines. Here we report that the pharmacokinetics and clearance of renal clearable gold nanoparticles (GS-AuNPs) are strongly dose-dependent once injection doses are above 15 mg kg : high dose expedited the renal excretion and shortened the blood retention. As a result, the no-observed-adverse-effect-level (NOAEL) of GS-AuNPs was >1000 mg kg in CD-1 mice.

Targeting orthotopic gliomas with renal-clearable luminescent gold nanoparticles.

A major clinical translational challenge in nanomedicine is the potential of toxicity associated with the uptake and long-term retention of non-degradable nanoparticles (NPs) in major organs. The development of inorganic NPs that undergo renal clearance could potentially resolve this significant biosafety concern. However, it remains unclear whether inorganic NPs that can be excreted by the kidneys remain capable of targeting tumors with poor permeability.

Renal clearable noble metal nanoparticles: photoluminescence, elimination, and biomedical applications.

Metal nanoparticles have demonstrated broad and promising biomedical applications in research laboratories, but how to fulfill their promises in the clinical practices demands extensive effort to minimize their non-specific accumulation in the body. In the past 6 years, we have developed a class of renal clearable noble metal nanoparticles with tunable visible and near-infrared emission, which can behave like small molecular contrast agents to be effectively eliminated through the kidneys. By taking advantage of the unique clearance pathway, we were able to gain some fundamental understanding of how engineering nanoparticles cleared out of the body through urinary system.

Tailoring Renal Clearance and Tumor Targeting of Ultrasmall Metal Nanoparticles with Particle Density.

Identifying key factors that govern the in vivo behavior of nanomaterials is critical to the clinical translation of nanomedicines. Overshadowed by size-, shape-, and surface-chemistry effects, the impact of the particle core density on clearance and tumor targeting of inorganic nanoparticles (NPs) remains largely unknown. By utilizing a class of ultrasmall metal NPs with the same size and surface chemistry but different densities, we found that the renal-clearance efficiency exponentially increased in the early elimination phase while passive tumor targeting linearly decreased with a decrease in particle density.

Dimerization of Organic Dyes on Luminescent Gold Nanoparticles for Ratiometric pH Sensing.

Synergistic effects arising from the conjugation of organic dyes onto non-luminescent metal nanoparticles (NPs) have greatly broadened their applications in both imaging and sensing. Herein, we report that conjugation of a well-known pH-insensitive dye, tetramethyl-rhodamine (TAMRA), to pH-insensitive luminescent gold nanoparticles (AuNPs) can lead to an ultrasmall nanoindicator that can fluorescently report local pH in a ratiometric way. Such synergy originated from the dimerization of TAMRA on AuNPs, of which geometry was very sensitive to surface charges of the AuNPs and can be reversely modulated through protonation of surrounding glutathione ligands.