As a bridge between individual atoms and large plasmonic nanoparticles, ultrasmall (core size <3 nm) noble metal nanoparticles (UNMNPs) have been serving as model for us to fundamentally understand many unique properties of noble metals that can only be observed at an extremely small size scale. With decades’efforts, many significant breakthroughs in the synthesis, characterization and functionalization of UNMNPs have laid down a solid foundation for their future applications in the healthcare. In this review, we aim to tightly correlate these breakthroughs with their biomedical applications and illustrate how to utilize these breakthroughs to address long-standing challenges in the clinical translation of nanomedicines. In the end, we offer our perspective on the remaining challenges and opportunities at the frontier of biomedical-related UNMNPs research.

The coming era of precision nanomedicine demands engineered nanoparticles that can be readily translated into the clinic, like that of molecular agents, without being hindered by intrinsic size heterogeneity and long-term body retention. Herein we report that conjugation of indocyanine green (ICG), an FDA-approved near-infrared (NIR) dye, onto an atomically precise glutathione-coated Au25 (GS-Au25) nanocluster led to a molecular-like photothermal nanoparticle (ICG4–GS-Au25) with significantly enhanced ICG photostability and tumor targeting. Under weak NIR light irradiation conditions, free ICG failed to suppress tumor growth but the original tumors were completely eradicated with ICG4–GS-Au25. In the meantime, “off-target” ICG4–GS-Au25 was effectively cleared out from the body like small-molecule drugs after glutathione-mediated biotransformation in the liver. These findings highlight the merits of molecular-like nanomedicines, offering a new pathway to meet FDA’s criteria for the clinical translation of nanomedicines.

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.T his requires af undamental 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.R enal-clearable AuNPs retain the advantages of the free drug, including rapid tumor targeting and high tumor vascular permeability.T he renal-clearable AuNPs also accelerated body clearance of off-target drug via renal elimination. These results clearly indicate that diverse in vivo transport behaviors of engineered nanoparticles can be used to reconcile long-standing paradoxes in the anticancer drug delivery.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

The past decade has witnessed a burst of study on ultrasmall gold nanoparticles. Unlike semiconductor quantum dots, ultrasmall gold nanoparticles have very diverse emission mechanisms, which are often involved in many structural factors such as size, valence state, surface ligands and crystallinity. In this frontier, we summarize our latest advancement in the fundamental understanding of emission mechanisms of ultrasmall gold nanoparticles, which are expected to help us more precisely control their emissions and broaden their applications from energy technologies to disease detection.

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Designing battery-type materials with good electrocapacitive performance and high electrical conductivity is necessary to improve the energy-storage capability of an battery-supercapacitor hybrid devices (BSH). Ternary metal oxides are synthesized by using a hydrothermal reaction with an extra metal of Mo, Fe, Cu, Zn, or Al incorporated in the nickel cobalt oxide as the battery-type material to enhance the electrical conductivity and generate numerous Faradaic reactions via the multiple oxidation state of transition metals. Because of the larger surface area of the nanosheet structure and the smaller charge transfer resistance with the participation of molybdenum, the best electrocapacitive performance among the ternary metal oxide electrodes is attained for the Ni x Co y Mo z O electrode, which is further optimized by tuning the Mo ratios in the precursor solution. An optimized Ni x Co y Mo z O electrode is prepared by using the Ni:Co:Mo ratio of 1:2:2. This electrode achieves an areal capacitance (C F ) of 2.94 F/cm 2 , which is higher than those for the binary metal oxide electrodes of Ni x Mo y O (1.11 F/cm 2 ), Co x Mo y O (1.63 F/cm 2 ), and Ni x Co y O (1.45 F/cm 2 ), inferring the success to improve the energy-storage ability of the electrode by incorporating more transition metals in the oxide as the electrocapacitive material. An BSH based on the Ni x Co y Mo z O positive electrode and an activated carbon negative electrode shows a C F value of 126 mF/cm 2 at 10 mA/cm 2 , a potential window of 1.8 V, and a maximum energy density of 22.02 Wh/kg at a power density of 3.50 W/kg. This result provides new blueprints for constructing multiple metal oxides as the battery-type material for achieving more Faradaic reactions and higher electrical conductivity, and hence for enhancing the energy-storage capability of an BSH.

HKUST-1@Fe3O4 chemically bonded core-shell nanoparticles have been prepared by growing HKUST-1 thin layers joined by carboxyl groups onto Fe3O4 nanospheres. These magnetic core-shell MOF nanostructures show exceptional catalytic activity for the oxidation of benzylic C-H bonds and they can be recovered by magnetic separation and reused without losing any activity.

Subtle changes in size can induce distinct responses of the body to hard nanomaterials; however, it is largely unknown whether just a few ethylene oxide unit differences in soft poly­(ethylene glycol) (PEG) molecules could significantly alter the renal clearance of small molecules. By systematically investigating in vivo transport of the representative renal clearable organic dyes, IRDye800CW after being conjugated with a series of PEG molecules with molecular weight (MW) below 10 kDa, we found a MW-dependent scaling law: PEG45 (MW = 2100 Da) is an optimized MW to generate the most efficient renal clearance for IRDye800CW by expediting the glomerular filtration of organic dyes and reducing their nonspecific interactions with background tissue. Moreover, the uniqueness of PEG45 can be generalized to other organic dyes such as ZW800-1 and fluorescein. This finding highlights the importance of low-MW PEGylation in tailoring in vivo transport of organic fluorophores, which would broaden their biomedical applications.