The photoluminescence (PL) of metal nanoclusters (NCs), originating from their molecule-like electronic structure, is one of the most intriguing properties of NCs. Although various strategies such as tailoring the size, structure, and chemical environment of NCs have shown to improve the PL, their quantum yields (QYs) are still lagging far behind those of conventional luminescent materials, including quantum dots and organic fluorophores. Herein, we report the synthesis of highly luminescent gold cluster assembly (GCA) from Zn2+-ion-mediated assembly of Au4(SRCOO–)4 clusters using mercaptocarboxylic acid as a protective ligand and reductant as well as a growth suppressor. The synergetic combination of unique aurophilic interactions among Au4 clusters and the rigidified chemical environment induced by metal ion chelation through carboxylate groups is responsible for the ultrabright greenish-blue fluorescence with a QY up to 90%. Furthermore, the unique flexibility of dis/reassembly and the aggregation-dependent strong fluorescence of GCA offer a great potential for applications in biodegradable and trackable drug delivery systems.

Nanoparticles have been extensively used to deliver therapeutic drugs to tumor tissues through the extravasation of a leaky vessel via enhanced permeation and retention effect (EPR, passive targeting) or targeted interaction of tumor-specific ligands (active targeting). However, the therapeutic efficacy of drug-loaded nanoparticles is hampered by its heterogeneous distribution owing to limited penetration in tumor tissue. Inspired by the fact that cancer cells can recruit inflammatory immune cells to support their survival, we developed a click reactionassisted immune cell targeting (CRAIT) strategy to deliver drug-loaded nanoparticles deep into the avascular regions of the tumor. Immune cell-targeting CD11b antibodies are modified with trans-cyclooctene to enable bioorthogonal click chemistry with mesoporous silica nanoparticles functionalized with tetrazines (MSNs-Tz). Sequential injection of modified antibodies and MSNs-Tz at intervals of 24 h results in targeted conjugation of the nanoparticles onto CD11b + myeloid cells, which serve as active vectors into tumor interiors. We show that the CRAIT strategy allows the deep tumor penetration of drug-loaded nanoparticles, resulting in enhanced therapeutic efficacy in an orthotopic 4T1 breast tumor model. The CRAIT strategy does not require ex vivo manipulation of cells and can be applied to various types of cells and nanovehicles.

Thanks to recent advances in the synthesis of high-quality inorganic nanoparticles, more and more types of nanoparticles are becoming available for medical applications. Especially, metal oxide nanoparticles have drawn much attention due to their unique physicochemical properties and relatively inexpensive production costs. To further promote the development and clinical translation of these nanoparticle-based agents, however, it is highly desirable to reduce unwanted interbatch variations of the nanoparticles because characterizing and refining each batch are costly, take a lot of effort, and, thus, are not productive. Large-scale synthesis is a straightforward and economic pathway to minimize this issue. Here, the recent achievements in the large-scale synthesis of uniform-sized metal oxide nanoparticles and their biomedical applications are summarized, with a focus on nanoparticles of transition metal oxides and lanthanide oxides, and clarifying the underlying mechanism for the synthesis of uniform-sized nanoparticles. Surface modification steps to endow hydrophobic nanoparticles with water dispersibility and biocompatibility are also briefly described. Finally, various medical applications of metal oxide nanoparticles, such as bioimaging, drug delivery, and therapy, are presented.