Nano Today
ReviewUltrasmall noble metal nanoparticles: Breakthroughs and biomedical implications
Introduction
Among all the engineered nanoparticles developed today, ultrasmall noble metal nanoparticles (UNMNPs), defined as noble metal nanoparticles with core size less than 3 nm, have been drawing extensive attentions from researchers for more than half a century because not only did they serve as unique platforms to study the size-dependencies at an extremely small size scale that are often hard to achieve with other nanomaterials but they also opened new pathways to address many challenges in areas such as energy and healthcare. Compared to semiconductor quantum dots, UNMNPs also have a long history of serving as model for the fundamental understandings of quantum-size effects in nanomaterials. These understandings were significantly advanced by many breakthroughs in the synthesis and characterization of UNMNPs, which eventually lead to various practical applications in the catalysis, energy storage, bioimaging and disease treatment. In the early date, few-atom metal nanoparticles (metal clusters) were successfully synthesized in gas matrices at low temperature and characterized with mass spectrometry conjugated with optical spectroscopies. For example, few-atom naked silver clusters Agn with well-defined atom number (n = 2–5), representing an important link between discrete Ag atoms and large Ag clusters, were synthesized in argon matrix by Huber et al. via cryophotoclustering technique and characterized by UV/Vis absorption spectroscopy [1]. These breakthroughs in the synthesis allowed us to unravel molecular-like electronic structures of noble metal clusters at extremely small size scales, which opened up the new era of noble metal nanoparticles beyond plasmonic ones that were first made by Faraday back in the 1800s [2]. In 1970s–80s, UNMNPs were successfully stabilized in solid matrices such as glasses and polymers [[3], [4], [5]]. The unique molecular-like properties of these ultrasmall metal nanoparticles later have found broad applications in chemical catalysis [6,7] and information storage [8]. For instance, Goodman et al. reported in the late 1990 s that Au clusters supported on titanium dioxide (TiO2) were able to catalyze the oxidation of carbon monoxide (CO) under low temperature and the catalytic reaction was strongly related to quantum size effect of the Au clusters [7]. This work elucidated the critical role of quantum size effects in determining the structure sensitivity and performance of supported metal catalysts and provided valuable guidance for the future design of nanostructured materials for catalytic purposes. Moreover, fluorescent Ag nanoclusters generated by the photoreduction of nanoscale silver oxide (Ag2O) were demonstrated by Dickson et al. in 2001 and they potentially could serve as a novel class of information storage medium, where data could be readily written on thin Ag2O films with blue light (<520 nm) and nondestructively read from the intense red fluorescence excited by green light (>520 nm) [8].
With the continuous advancement of nanochemistry, ultrasmall metal nanoparticles not only can be made water soluble but also are precisely controlled in the size down to the single atom level. In addition to precise size control, UNMNPs can be doped with other elements and the surface chemistries of these noble metal nanoparticles can also be fine tuned. These latest breakthroughs of UNMNPs significantly broadened their biomedical applications at both in vitro and in vivo level. In this review, we will discuss UNMNPs in a way that the latest breakthroughs in this field will be tightly integrated with their biomedical applications; so that the beauty of UNMNPs in their synthesis, fundamental physical and physiological properties as well as biomedical applications can be coherently correlated (Fig.1). In terms of the biomedical applications, we will emphasize the in vivo applications since in vivo use of UNMNPs has mushroomed significantly over the last few years and many in vitro applications have already been summarized in several excellent reviews [[9], [10], [11], [12]]. The major breakthroughs that are covered here were divided into three categories: 1) the breakthroughs in the preparation of UNMNPs, including precisely size-controlled synthesis and doping (alloying) of foreign atoms; 2) the breakthroughs in understanding the physical properties of UNMNPs, including their structure and optical properties; 3) the breakthroughs in understanding the physiological properties UNMNPs, including their in vivo stability and clearance pathway, tumor targeting and toxicity. In the final section, we will discuss some current challenges and questions encountered in the clinical translation of UNMNPs.
Section snippets
Precisely size-controlled synthesis
Heterogeneity in size is generally considered an intrinsic property of nanomaterials, which, however, has been a serious road block in the clinical translation of nanomedicines because heterogenous size distribution can create many uncertainties in reproducing nanomedicines with the same therapeutic efficacy on the large scale. Thus, precise control of nanomaterials with size down to atomic level is highly appreciated, which has also been a long journey for chemists. To date, gold [[13], [14],
Structures of UNMNPs
The structure understanding of UNMNPs has progressed considerably in recent decade owing to the breakthroughs in their precisely chemical synthesis and the advancement of characterization methods. Atomically precise UNMNPs with molecular purity have enabled their crystallization and subsequent determination of their total structure through X-ray crystallography. To date, crystal structures of dozens of atomically precise UNMNPs (including alloying nanoparticles) have been reported since the
In vivo stability and clearance pathway
For UNMNPs used in vivo, their stability in the body is of paramount importance as it directly affects the pharmacokinetics, biodistribution, clearance profile and toxicity of UNMNPs. Both the core metal and surface ligands influence the in vivo stability of UNMNPs. Compared to metals (e.g., Au, Pt) with the highest nobility, nanoparticles composed of less noble metals (e.g., Ag, Cu) tend to be less stable in vivo due to their reduced chemical inertness [215,216]. AgNPs, for example, are well
Conclusion and perspective
In summary, we briefly summarized the breakthroughs of UNMNPs over the past decade in terms of the preparation (precisely-controlled synthesis, doping and alloying), understanding of their physical properties (structures and optical characteristics) as well as physiological properties (in vivo stability, clearance, tumor targeting and toxicity). The related biomedical applications enabled by these breakthroughs were also demonstrated. Compared with their large counterparts, UNMNPs do offer many
Acknowledgements
J.Z. acknowledges the financial support from National Institutes of Health (NIH) (1R01DK103363), Cancer Prevention Research Instituted of Texas (CPRIT) (RP140544, RP120588) and the start-up fund from the University of Texas at Dallas.
Xingya Jiang received his BS in Applied Chemistry from Beijing Institute of Technology in 2014 and joined Dr. Jie Zheng’s group at the University of Texas at Dallas the same year as a graduate student. He is now a PhD candidate with research interests spanning from the design and synthesis of nanomedicines to their novel biomedical applications.
References (327)
- et al.
Inorg. Chem.
(1978) Philos. Trans. R. Soc. London
(1857)- et al.
J. Am. Chem. Soc.
(1978) Phys. Rev. B
(1983)- et al.
J. Am. Chem. Soc.
(1979) - et al.
Science
(1979) - et al.
Science
(1998) - et al.
Science
(2001) - et al.
Nano Today
(2014) - et al.
Nano Today
(2011)
Nanomed. Nanobiotechnol.
Chem. Mater.
J. Am. Chem. Soc.
J. Mater. Chem.
J. Am. Chem. Soc.
Acs Nano
Chem. Mater.
J. Am. Chem. Soc.
Nano Lett.
Proc. Natl. Acad. Sci.
Chem. Mater.
Small
J. Phys. Chem Lett.
J. Phys. Chem Lett.
Nature
J. Phys. Chem. C
Angew. Chem.
J. Am. Chem. Soc.
J. Am. Chem. Soc.
Philos. Trans. R. Soc. Lond.
J. Phys. Chem. C
J. Phys. Chem Lett.
Chem. Soc. Rev.
RSC Adv.
Chem. Rev.
Recl. Trav. Chim. Pays-Bas
J. Chem. Soc., Chem. Commun.
J. Chem. Soc., Chem. Commun.
J. Chem. Soc., Dalton Trans.
Eur. J. Inorg. Chem.
Chem. Soc. Rev.
Inorg. Chim. Acta
Angew. Chem. Int. Ed.
Pure Appl. Chem.
Science
J. Phys. Chem. B
J. Phys. Chem. B
J. Am. Chem. Soc.
J. Am. Chem. Soc.
Nanotechnology
Cited by (126)
In situ tuning and investigating the growth process of size controllable gold nanoparticles and statistical size prediction analysis
2024, Colloids and Surfaces A: Physicochemical and Engineering AspectsCovalent organic framework-supported ultrasmall Rh nanoparticles as peroxidase mimics for colorimetric sensing of cysteine
2023, Journal of Colloid and Interface ScienceUltrasmall, elementary and highly translational nanoparticle X-ray contrast media from amphiphilic iodinated statistical copolymers
2023, Acta Pharmaceutica Sinica BImproved methanol electro-oxidation reaction on PdRh-PVP/C electrodes
2023, International Journal of Hydrogen EnergyCitation Excerpt :Stabilized metal-based nanoparticles (MNPs; nanocrystalline metal cores surrounded by a protecting shell, namely organic ligand or polymers) have attracted considerable attention due to their unusual chemical and physical properties that can lead to various applications in different areas such as nanocatalysis, biolabeling, sensing, biomedicine, and solar energy [1–6].
Antimicrobial Properties of Silver and Gold Nanomaterials
2023, Encyclopedia of Nanomaterials
Xingya Jiang received his BS in Applied Chemistry from Beijing Institute of Technology in 2014 and joined Dr. Jie Zheng’s group at the University of Texas at Dallas the same year as a graduate student. He is now a PhD candidate with research interests spanning from the design and synthesis of nanomedicines to their novel biomedical applications.
Bujie Du is a graduate student at the Chemistry & Biochemistry department of the University of Texas at Dallas. She received her BS in Chemistry from Beijing Institute of Technology. In fall 2014, she started her graduate studies with Prof. Jie Zheng at UT Dallas, focusing on the fundamental studies of nano-bio interactions of engineered nanoparticles.
Yingyu Huang was born in 1993 in Hubei, China. He received his BS in Chemistry in 2015 from Beijing Institute of Technology. Currently he is pursuing his PhD degree under the supervision of Dr. Jie Zheng at the University of Texas at Dallas. His current research focus is on the synthesis, properties and biomedical applications of luminescent gold nanoparticles.
Dr. Jie Zheng received his PhD degree from Georgia Institute of Technology in 2005. After three-years postdoctoral research at Harvard University, he joined the chemistry department at the University of Texas at Dallas as an assistant professor. He is now the associate professor of Chemistry & Biochemistry at the University of Texas at Dallas and also the adjunct associate professor of Urology at the University of Texas Southwestern Medical Center. His research interests focus on luminescent metal nanostructures and understanding of nano–bio interactions and transport at both in vitro and in vivo levels.