Direct heterogeneous nucleation (Figure 2A) is among the most frequently exploited pathways for constructing MHNCs in the form of binary and ternary assemblies composed of diverse associations of magnetic, metal, and materials. Hetero-dimer and higher-order hetero-oligomer MHNCs have been envisioned as key elements on which new technological solutions may be envisaged, especially in fields where multifunctionality and multitasking capabilities are intrinsically needed (e.g., sensing, imaging, drug delivery, and therapy in biomedicine). For example, it has been proposed that distinct material modules of a HNC can be used as anchoring platforms for the site-specific attachment of selected biomolecules or ligands (Jun et al., 2007; Gao et al., 2009; Bigall et al., 2012; Lim and Majetich, 2013). In addition, while a metal or semiconductor domain can enable optical detection (e.g., via excitonic or LSPR absorption, or photoluminescence), a magnetic module can be utilized for complementary purposes, such as for magnetic resonance imaging (MRI), optical imaging, and magnetic separation (Choi et al., 2006, 2008; Jun et al., 2007; Jiang et al., 2008; Xu et al., 2008; Gao et al., 2009; Schladt et al., 2010; Bigall et al., 2012; Lim and Majetich, 2013). The existence of bonding heterointerfaces through which dissimilar materials can electronically communicate has clearly been recognized to impact on the magnetic (Xu et al., 2008; Lee et al., 2010a; Umut et al., 2012; Pineider et al., 2013; Kim and Song, 2014; Schick et al., 2014; López-Ortega et al., 2015; Velasco et al., 2015), optical (Levin et al., 2009; Korobchevskaya et al., 2011; Comin et al., 2012), transport (Lee et al., 2010a), magneto-optical (Li et al., 2005; Armelles et al., 2013), (electro)catalytic (Yin et al., 2008; Wang et al., 2009a, 2010; Wu et al., 2009; Lee et al., 2010b; George et al., 2011a, 2013; Jang et al., 2011b; Lin and Doong, 2011; Chen et al., 2012; Sun et al., 2012), and energy-storing properties of appropriately engineered MHNCs (Liu et al., 2015). Examples of MHNCs derived from heterogeneous deposition pathways are collected in Figures 2B–Q.

Thermal decomposition of metallorganic precursors in the presence of preformed noble metal, Fe₃O₄, FePt, or UO₂ seeds in non-coordinating solvents, such as octadecene (ODE) or phenyl ether containing oleic acid (OLAC), oleyl amine (OLAM), and/or tri-n-octyl phosphine (TOP) surfactants at 200–300°C has enabled access to hetero-dimer HNCs made of two nearly spherical and/or cubic-shaped domains epitaxially interconnected, such as of Me–Fe₃O₄ (Me = Au, AuAg, PtPd, AuPd, AuPt, Pt, Pd, Ni, Cu) (Yu et al., 2005; Shi et al., 2006b; Choi et al., 2008; Wei et al., 2008; Wang et al., 2009a, 2010; George et al., 2011a, 2013; Jang et al., 2011a; Lin and Doong, 2011; Nakhjavan et al., 2011; Zhai et al., 2011; Leung et al., 2012; Sun et al., 2012; Kim and Song, 2014; Victor et al., 2015), Fe₃O₄–MnO (Lee et al., 2012), Au–MnO (Choi et al., 2008; Schladt et al., 2010), Fe₃O₄–CdSe (Tao et al., 2009), UO₂–In₂O₃ (Wu et al., 2011a), and FePt–YZ (YZ = CoFe₂O₄, Co, Ni, Fe, CdS, ZnS, PbS, PbSe, CdSe, In₂O₃, Fe₃O₄, MnO) (He et al., 2009; Lee et al., 2010a; Wu et al., 2011a; Schladt et al., 2012; Liu et al., 2014; Yang et al., 2015), respectively. Depending on the geometric features of the two-component domains, these heterostructures exhibit various morphological profiles, spanning from peanut-, dumbbell-, brick- to flower-like (Figures 2B–D). In most cases, the non-negligible difference in lattice parameters has been considered to be the main driving force that promotes extensive segregation of the concerned materials into discrete domains, oriented relative to one another so as to guarantee coherent small-area heterointerfaces and minimal misfit strain. Among these cases, the formation mechanism of Au–Fe₃O₄ hetero-dimers was investigated in detail (Yu et al., 2005; Wei et al., 2008). The solvent was found to play a fundamental role in regulating the density of Fe₃O₄ nucleation sites on the Au seeds. The dumbbell-like configuration yielded by reactions performed in non-polar media was explained by invoking induction of polarization charge at those regions of the Au seeds where Fe₃O₄ had initially been deposited. Such polarization resulted in corresponding electron density depletion at other locations, where further nucleation events could in fact be inhibited. By contrast, in syntheses carried out in a more polar electron-donor solvent, any electron deficiency generated over the Au surface could be compensated for and leveled off by the medium molecules, which contributed to render the seed a more suitable ground either for the installation of multiple Fe₃O₄ “petals” or for the accommodation of a uniform Fe₃O₄ coverage (Yu et al., 2005; Wei et al., 2008; Wang et al., 2010).

In additional mechanistic investigations on other metal/metal oxide and metal/semiconductor systems, the transition from dumbbell- to flower-like geometry was controllably achieved by increasing the temperature and/or relative precursor to seed proportions (Shi et al., 2006b; Choi et al., 2008; Jiang et al., 2008; Wei et al., 2008; He et al., 2009; Schladt et al., 2010; Zhai et al., 2011). In some cases, the nature of ligands that were originally bound to the surface of the starting seeds or were added during the seeding stage was found to be critical to driving the preference for a hetero-dimer topology over a core@shell one, which pointed to the influence of kinetic processes on topology selection (Yu et al., 2005; Choi et al., 2008; Jiang et al., 2008; Wei et al., 2008; He et al., 2009; Lee et al., 2010a; Schladt et al., 2010; Nakhjavan et al., 2011; Zhai et al., 2011).

In an effort to rationalize the formation of peanut-shaped FePt–In₂O₃ hetero-dimer MHNCs (Wu et al., 2011a), the crystallographic relationships holding between two materials were first investigated on the basis of the coincidence site lattice theory (CSLT) (Randle, 1997; Kwon and Shim, 2005; Kwon et al., 2006; McDaniel and Shim, 2009). In the CSLT approach, starting from the assessment of the relative domain orientations in a MHNC upon analysis of the relevant HRTEM data, the degree of matching between points of the concerned lattices and the frequency at which this correspondence occurs along the relevant heterojunction planes can be studied. Several couples of facets of the FePt and In₂O₃ lattices were identified to be potentially involved in the formation of satisfactorily lattice-matched heterointerfaces. An empirical law, referred to as a “bonding energy criterion,” was then proposed to explain the preference for the few particular relative FePt to In₂O₃ lattice orientations that were observed experimentally in the hetero-dimers: instead of assuming that In₂O₃ overgrowth took place on the facets of the FePt seeds, at which lattice mismatch could be minimized, the epitaxial deposition of In₂O₃ was considered to most be favored on the FePt crystal facets for which the first atomic monolayer of the deposited In₂O₃ had the strongest chemical affinity (Wu et al., 2011a).

By a reverse reaction scheme, hetero-dimers made of FePt–Au (Mokari et al., 2005; Choi et al., 2006; Shi et al., 2006b; Selvan et al., 2007; Wark et al., 2008; He et al., 2009; Franchini et al., 2010; Zeng et al., 2010; Mao et al., 2011; Krylova et al., 2012; Zhu et al., 2013), CoPt₃–Au (Pellegrino et al., 2006; Pazos-Perez et al., 2007; Krylova et al., 2012), and Fe₃O₄–Ag (Zhang et al., 2006; Jiang et al., 2008; Yang and Ying, 2009; Huang et al., 2011; Peng et al., 2011; Mao et al., 2013) were generated upon reduction of Au(I)-, Au(III)-, or Ag(I)-ligand complexes onto FePt, CoPt₃, and Fe₃O₄, seeds, respectively, with mild reducing agents (alkyl amines, alkyl diols, Ar/H₂ atmosphere) at moderate temperatures (<120°C) (Figures 2E–G). With the introduction of an extra reaction step, γ-Fe₂O₃–Cu₂O and Au–Fe₃O₄ heterodimer MHNCs were produced from parent γ-Fe₂O₃–Cu (Mirtchev et al., 2014) and Au–Fe (Jiang et al., 2016) hetero-dimers upon post-synthesis air oxidation of their Cu and Fe sections, respectively.

The properties of these magnetic/metal/semiconductor MHNCs have been found to clearly diverge from those of the individual components alone. For example, the luminescence of semiconductor modules is severely quenched due to the metal contact promoting electron transfer, hence, decreasing the probability of radiative electron–hole recombination (de Mello Donegà, 2011; Sitt et al., 2013; Banin et al., 2014). The LSPR features of coinage-metal sections are largely modified, depending on the dielectric characteristics of their proximal neighbors (Mokari et al., 2005; Shi et al., 2006b; Yang et al., 2006a,b, 2009; Yang and Ying, 2009; Pazos-Perez et al., 2007; Selvan et al., 2007; Wark et al., 2008; He et al., 2009; Franchini et al., 2010; Zeng et al., 2010). In addition, the relevant magnetic parameters of magnetic domains are often found to unpredictably deviate from those of the otherwise isolated components (Choi et al., 2006; Huang et al., 2011; Mao et al., 2011; Wu et al., 2011b; Leung et al., 2012; Zhu et al., 2013), indirectly revealing an influence of interfacial electron communication on the electronic and magnetic behavior (Pellegrino et al., 2006; Shi et al., 2006b; Zhang et al., 2006; Pazos-Perez et al., 2007; Jiang et al., 2008; Yang and Ying, 2009; Yang et al., 2009).

Further mechanistic knowledge on MHNC formation has been grasped upon analysis of the topological evolution of MHNCs as a function of time and of systematically varied synthesis parameters, as well as on the basis of dedicated control experiments. The facile tunability of the geometric features of CoPt₃–Au, FePt–Au, and Fe₃O₄–Ag hetero-dimers can be rationalized on considering that the CoPt₃ and Fe₃O₄ seeds utilized in the reported circumstances acted as red-ox active heterogeneous catalysts that exhibited varying degrees of reactivity toward reduction of the utilized Au(I)- or Au(III)- and Ag(I)-ligand complex precursor, depending on their size and faceting. In the particular case of bimetallic CoPt₃–Au and FePt–Au hetero-dimers, it was ascertained that the reduction of Au(I)- or Au(III)-complexes by metal species in the CoPt₃ and the FePt seeds, respectively, triggerred the Au nucleation event, while subsequent growth of Au domain was fed by reduction of Au(I) or Au(III) ions at the seed surface performed by the external reducing agent (hexadecyl amine) (Krylova et al., 2012). The size to which the secondary metal domains could ultimately be grown was regulated through adjustment of seed to precursor concentration ratio and temperature, which indeed dictated the rate and extent of secondary metal-ion incorporation into the seeds (Pellegrino et al., 2006; Jiang et al., 2008; Huang et al., 2011; Peng et al., 2011; Mao et al., 2013; Zhu et al., 2013). It has been learnt that, in general, when interfacial strain is not prohibitively high, smaller-sized seeds may accommodate a continuous thick shell of the foreign materials as a means of reducing their excessive surface energy (Lee et al., 2012). On the other hand, when the seeds expose crystallographically and/or chemically inequivalent facets and/or the emergent interfacial strain, being highly dependent on surface curvature, may not be alleviated, heterodimer-type topologies are preferred over core@shell ones (Pazos-Perez et al., 2007; Jiang et al., 2008; Zhu et al., 2013).

The formation of hetero-oligomers with binary composition has frequently been reported. When faceted NCs enclosed by relatively large and stable facets with comparable surface atomic structure and/or reactivity are utilized as seeds, growth of numerous domains of the secondary components may occur on the equivalent facets or on the many surface sites (e.g., defects, edges) where nucleation may be kinetically favored and/or interfacial strain may be minimized. These circumstances may lead to heterostructures made of patchy or flower-like architectures, in which multiple satellites of the secondary material are assembled around a single central core that corresponds to one of the starting seeds (Kwon et al., 2006; McDaniel and Shim, 2009; Peng et al., 2011; Zhai et al., 2011; Hou et al., 2012; Lee et al., 2012; Mao et al., 2013; Yu et al., 2015). Depending on the specific case, the use of appropriate surface-binding surfactants (Mao et al., 2013) or judicious adjustment of the reducing conditions (Zhu et al., 2013) have been identified as effective strategies for either accentuating or leveling off the reactivity of the available seed locations, thereby modulating the frequency of heterogeneous nucleation events (Figures 2H–J). In another interesting study (Peng et al., 2011), during heterogeneous Ag deposition on spherical Fe@Fe_xO_y seeds in organic media, high-order Fe@Fe_xO_y–Ag hetero-oligormers gradually converted to lower-order Fe@hollow-Fe_xO_y–Ag hetero-oligomers and, finally, to hollow-Fe_xO_y–Ag hetero-dimers (Figures 2K–N). During this progression, the average Ag domain and Fe_xO_y shell sizes increased, while the inner Fe cores of the seeds shrunk until disappearance. The time evolution of the density and size of the Ag domains was found to be consistent with the classical LaMer nucleation and Ostwald ripening mechanisms, according to which NCs are generated from a temporally limited nucleation burst, followed by the larger NCs within the population growing at the expense of the dissolution of the smaller, unstable ones. Concomitantly, the Fe cores of the Fe@Fe_xO_y modules (i.e., the original seeds) underwent oxidation and entered a Kirkendall diffusion regime (An and Hyeon, 2009; Zhang et al., 2009; Wang et al., 2013b) (most likely, driven by trace O₂, Ag⁺, and/or NO3− ions), which eventually led to extensive Fe dissolution and creation of hollow-Fe_xO_y domains with thick walls (Figure 2N) (Peng et al., 2011).

Conceptually replicating the total-synthesis approach used to build complex organic molecules equipped with different functional moieties, elaborate multicomponent hetero-oligomer MHNCs with progressively higher nuclearity order have been engineered by performing chemoselective heterogeneous nucleation steps on preformed heterostructured seeds (Figure 2A). To this purpose, well-known chemical pathways for growing the target materials were rationally combined and applied under appropriate conditions. For example, Fe₃O₄–Au–PbSe hetero-trimers (Figure 2O) were synthesized by directing deposition of PbSe onto Fe₃O₄–Au dumbbell-shaped hetero-dimer seeds upon reaction with Pb/Se-surfactant complexes (Shi et al., 2006a,b). Interestingly, the tertiary cubic-phase PbSe component grew out of the Au domains anisotropically via a solution–liquid–solid growth mechanism (Cozzoli et al., 2006), developing into rod-shaped sections that eventually detached from the hetero-dimer seeds and transferred into the solution (Shi et al., 2006a). Similarly, linear Fe₃O₄–Pt–Me (Me = Au, Ag, Ni, Pd) and Fe₃O₄–Pt–Me_xS_y (Me = Pb, Cu) hetero-trimers (Figures 2P–Q) could be constructed upon site-specific deposition of the desired tertiary metal or metal-sulfide component on the Pt domain of Fe₃O₄–Pt heterodimer seeds, a reaction that was not accompanied by the formation of other isomer side-products (Buck et al., 2012). This reaction outcome is intriguing, in that it can be regarded as a NC-related analogue of regiospecificity in molecular systems, in which out of several products that may be formed with different spatial arrangements of their functional moieties, only one is ultimately obtained. On the basis of competently designed control experiments, the observed chemoselectivity was preliminarily assumed to correlate with an electron enrichment of the Pt domains in the Fe₃O₄–Pt hetero-dimer seeds due to charge transfer from the adjacent Fe₃O₄ domain (a process not achievable in isolated Pt nanoparticles, in fact). Further microscopic investigations of chemoselectivity in the formation of Ag–Pt–Fe₃O₄ hetero-trimer MHNCs (Hodges et al., 2015) revealed an initial indiscriminate Ag nucleation onto both the Pt and Fe₃O₄ surfaces of Fe₃O₄–Pt seeds, followed by surface diffusion and coalescence of Ag onto the Pt surface to yield the final Fe₃O₄–Pt–Ag hetero-trimer product. The size of the Ag domain of Fe₃O₄–Pt–Ag correlated with the total surface area of the Fe₃O₄–Pt seeds, which was consistent with a mechanism of Ag coalescence through a surface-mediated process. Additionally, small iron oxide islands on the Pt surface of the Fe₃O₄–Pt seeds (deposited during their synthesis) were identified as defining the morphology of the Ag domain (Hodges et al., 2015). In line with these results, further studies have been successfully extended to the case of ternary Au–Pt–Cu_xS_y HNCs synthesized upon chemoselective metal-sulfide deposition over preformed Pt–Au hetero-dimers (Bradley et al., 2015).

To obtain other ternary MHNC isomers, the concept of a solid-state protecting group was borrowed from its organic-chemistry analogue and introduced into a typical colloidal MHNC synthesis (Hodges et al., 2014). A thin amorphous iron oxide shell was installed onto the Pt domain of preformed Fe₃O₄–Pt hetero-dimers to serve as a solid-state protecting group that isolated the Pt moiety, thus re-directing the nucleation of a third domain of Ag or Au to an otherwise disfavored site, namely the Fe₃O₄ domain. This strategy thus allowed producing the distinct and otherwise inaccessible Ag–Fe₃O₄–Pt and Au–Fe₃O₄–Pt hetero-trimer isomers, respectively.

Occasionally, heterogeneous nucleation processes have been captured to interplay and/or compete with red-ox replacement, cation exchange and the Kirkendall reaction pathways, leading to heterostructures that, however, embody an irregular distribution of their chemical composition or contain voids (Wark et al., 2008; Yang et al., 2009; Liu and Walker, 2010; Wang et al., 2013a). In the realm of MHNCs, an exception is provided by the outcome of the reaction of presynthesized metallic α-Fe NCs with nickel acetylacetonate (Slaton et al., 2015). Mechanistic insight into this system indicated that galvanic replacement of Fe for Ni took place within the α-Fe NCs, followed by rapid oxidation of both Ni and Fe to yield multidomain alloyed-Fe_xNi_y–Me₃O₄ (Me = Fe, Ni) heterostructures.

Detailed investigations on the formation of heterostructures based on either FePt or γ-Fe₂O₃ and metal chalcogenides of the type MeX (Me = Cd, Zn, Hg; X = S, Se) (Gu et al., 2004; Kwon and Shim, 2005; Kwon et al., 2006; Selvan et al., 2007; Zanella et al., 2008; He et al., 2009; McDaniel and Shim, 2009) have revealed that interfacial strain emerging upon crystallization and induced coalescence in the early post-deposition stages impacted on their topological evolution (Figure 3A). Examples of hetero-dimer and hetero-oligomer HNCs derived from these pathways are displayed in Figures 3B–E. Upon reacting either γ-Fe₂O₃ or FePt seeds with suitable organometallic precursors that were added sequentially at low temperature, a highly defective and amorphous MeX layer was initially deposited. Upon prolonged heating at 280°C, the amorphous MeX shell gradually crystallized, consequently exerting strain across the formed lattice-mismatched seed/MeX heterojunctions. Over time, the shell coalesced, reshaping into a discrete MeX grain aside of the γ-Fe₂O₃ seed (Gu et al., 2004; Kwon and Shim, 2005; Kwon et al., 2006; Selvan et al., 2007; Zanella et al., 2008; He et al., 2009). Such evolution was explained by considering that the large junction tension in the initially attained core@shell nanostructures could be greatly relieved during the annealing at high temperature, as supply of extra thermal energy promoted coalescence and dewetting of the crystallizing shell into a separate domain aside, which resulted in an obvious reduction of the interfacial area shared between the two materials. This interfacial energy gain could thus be large enough to compensate for the proportionally smaller increase in the overall surface energy that eventually accompanied formation of the non-core@shell heterostructure (Gentili et al., 2012; Thompson, 2012). In the case of the γ-Fe₂O₃–MeX system, the observed topological evolution was rationalized on the basis of the CSLT theory (Randle, 1997; Kwon and Shim, 2005; Kwon et al., 2006; McDaniel and Shim, 2009). Indeed, the mean number of MeX domains that could be accommodated on each γ-Fe₂O₃ seed (Figures 3B,C) correlated with the seed size and with the degree of lattice match achievable at the relevant γ-Fe₂O₃/MeX heterointerfaces (Kwon and Shim, 2005; Kwon et al., 2006; McDaniel and Shim, 2009). Adjustment of the ligand environment and of the growth kinetics regime (McDaniel and Shim, 2009) could facilitate installation of either one or multiple CdS sections that developed anisotropically out of γ-Fe₂O₃ seeds (Figures 3D,E). These magnetic-oxide/semiconductor MHNCs could still exhibit appreciable photoluminescence from the semiconductor MeX domains, while retaining the typical superparamagnetic behavior of nanoscale spinel-cubic iron oxide (Gu et al., 2004; Kwon and Shim, 2005; Kwon et al., 2006; Selvan et al., 2007; Zanella et al., 2008; He et al., 2009), which suggests their usefulness as bifunctional probes for dual-mode bioimaging (Selvan et al., 2007; Gao et al., 2009).

Only recently, it has been realized that post-deposition crystallization-dewetting mechanism could be involved in the formation of magneto-plasmonic hetero-dimer MHNCs more frequently than initially assumed. In fact, accurate experimental observations have allowed discrediting previous mechanistic assumptions, according to which several types of the previously developed hetero-dimer MHNCs would result from direct facet-selective heterogeneous nucleation of the secondary domain onto the preexisting seeds. On the basis of the following significant reports, a mechanistic revisitation of earlier synthetic achievements should be made for the broad family of metal/iron ferrite heterostructures synthesized starting from metal seeds. The first case study that is worth mentioning concerns the formation of AuPt–Fe₃O₄ hetero-dimer MHNCs (George et al., 2011a). The starting AuPt seeds were initially captured to convert to AuPt@Fe₃O₄ core@shell MHNCs at relatively low temperature (190°C). Subsequently, under harsher conditions (280–320°C), the Fe₃O₄ shell partially dewetted and restructured into a discrete spherical Fe₃O₄ domain attached aside each AuPt seed core. Along this process, the AuPt domain retained a thin discontinuous Fe₃O₄ shell on the hemispherical region that was diametrically opposite to the location of the major coalesced Fe₃O₄ domain. A similar mechanism relying on the dewetting of an unstable thin Fe₃O₄ shell formed on the metal seeds at early to intermediate stages may thus be expected to be involved in the formation of other Me–Fe₃O₄ (Me = Au, AuPt) hetero-dimers. Actually, interesting “tug-of-war” etching-destabilization experiments, aimed at probing the chemical reactivity of these heterostructures (Wang et al., 2009b; Lee et al., 2010b; George et al., 2011a), have shown that Au could be selectively leached out from Me–Fe₃O₄ hetero-dimers upon oxidation with I₂ at near room temperature. Depending on the topological profile of the starting hetero-dimers, either nearly spherical Fe₃O₄ NCs, each bearing a concavity, or peanut-/dumbbell-like solid-hollow homo-dimer Fe₃O₄ NCs were obtained. In all cases, the formed concave region or void was exactly commensurate to the volume that was originally occupied by the Au domain; in addition, in the particular case of AuPt–Fe₃O₄, I₂-driven oxidation of the AuPt domain led to a nanocontainer section that encased a residual Pt domain (George et al., 2011a). The formation of such exotic nanostructures with concave surfaces or extended cavities indirectly discredited the earlier assumption that the metal (hemi)domain of these hetero-dimer MHNCs was totally “naked,” that is, in direct contact with the external environment; in contrast, the metal-etching experiments unveiled that the portion of the metal, which was not nested in the Fe₃O₄ domain, could accommodate a thin, porous (hence, permeable), or discontinuous Fe₃O₄ shell that guaranteed its chemical accessibility, a feature that should be taken into account to explain their (electro)catalytic performance (Yin et al., 2008; Wang et al., 2009a, 2010; Wu et al., 2009; Lee et al., 2010b; George et al., 2011a, 2013; Lin and Doong, 2011; Chen et al., 2012; Sun et al., 2012).

A very recent detailed study has unexpectedly revealed participation of dewetting also in the formation of all-metallic Au–Pt-alloy hetero-dimer MHNCs (Kwon et al., 2015). According to this report, heteroepitaxial deposition of Au on the Pt-alloy seeds proceeded through the initial formation of a thin Au shell that exerted high stress onto the seed underneath. In the subsequent reaction stage, the lattice strain intensified to the point of inducing Au dewetting, a process that, in turn, allowed for strain relaxation. Thus, the Au/Pt-alloy heterostructures underwent a topological transition from a core@shell to a dumbbell-like configuration.

An interesting technique to synthesize magneto-plasmonic hetero-dimer MHNCs relies on performing the deposition of a secondary metal component on seeds located at the liquid/liquid interface between immiscible liquid phases (Figure 4A). Examples of MHNCs derived by this strategy are shown in Figures 4B–G. In the reported procedure, an aqueous solution containing a Au(III) or Ag(I) salt was put in contact with an immiscible organic phase that contained surfactant-capped Fe_xO_y or FePt seeds dissolved in a non-polar solvent, such as dichlorobenzene, dichloromethane, hexane, or DOE (Gu et al., 2005; Pan et al., 2010). Upon ultrasound irradiation under inert atmosphere, an emulsion formed, which consisted of a continuous aqueous phase containing “colloidosomes,” organic microdroplets stabilized by the hydrophobic-capped seed NCs that had self-assembled at the organic/water interfaces (Dinsmore et al., 2002). Under these conditions, the seeds provided catalytically active sites onto which the Ag⁺ or AuCl4− ions were reduced to the respective metals during the ultrasonication (Gu et al., 2005). As the seeds were only partially exposed to the aqueous phase, metal deposition was spatially restricted to a small region of their surface and proceeded self-catalytically, thus allowing the formation of only one metal domain on each seed (Figures 4B–E). The “colloidosome”-based approach was extended to the synthesis of solid-Ag/hollow-γ-Fe₂O₃ hetero-dimer MHNCs (Figures 4F,G) starting from hollow γ-Fe₂O₃ seeds prepared by manipulating the Kirkendall mechanism (An and Hyeon, 2009; Zhang et al., 2009; Pan et al., 2010; Wang et al., 2013b; Qi et al., 2015). These MHNCs were used to accommodate a site-differential surface distribution of biomolecules that were exploitable for biomedical purposes (An and Hyeon, 2009; Gao et al., 2009; Pan et al., 2010).

A few reports have documented the synthesis of hetero-dimer MHNCs by one-pot approaches that do not involve the introduction of seeds presynthesized in a separate environment (Figure 5A). In these cases, all reagents required to construct the heterostructures are loaded together into the same solvent/surfactant medium since the beginning of the synthesis. Conditions may be serendipitously identified under which the specific nucleation and growth processes that underlie the formation of each different material module require distinct activation energies and are thus triggered at substantially different rates, thus proceeding in sequence with negligible temporal overalap (Erdemir et al., 2009). Liquid-cell TEM imaging, a technique that has very recently been advanced to the point of allowing NC evolution to be tracked directly in solution in real time (Ross, 2015), has unambiguously confirmed that self-regulated homogeneous and heterogenous nucleation dynamics can indeed be operative in the formation of MHNCs (Liang et al., 2015). Figures 5B–E collects examples of MHNCs derived by such pathways.

Co₉S₈–PdS_x hetero-dimer MHNCs with acorn profile (Figures 5A,B) were produced by co-pyrolysis of the corresponding cobalt and copper carboxylate precursors in the presence of alkylthiols as the sulfur source (Teranishi et al., 2004, 2007a). As these metal sulfides are only partially miscible and feature large interfacial energy, a solid–solution could not be created, whereas phase segregation of two materials took place instead. During the reaction, selective homogeneous nucleation and growth of one material did occur first; then, as the critical miscibility threshold was reached, the second component started to develop, progressing through an interface of graded composition (Erdemir et al., 2009). Similarly, Au–Ni hetero-dimer MHNCs (Figure 5C) were obtained upon heating HAuCl₄ and Ni(NO₃)₂ in octadecyl amine (ODA) at 120°C, during which initially generated Au seeds triggered the otherwise kinetically hindered reduction of Ni²⁺–ODA complexes at their surface (Wang and Li, 2010).

Another interesting case is represented by the evolution of FePt–Fe_xO_y hetero-dimers for which independent domain size tunability could be easily achieved (Figure 5D). The two material modules formed sequentially in two steps during the reaction of platinum acetylacetonate and Fe(CO)₅ in hot OLAM/OLAC/ODE mixtures (Figuerola et al., 2008). Initially, homogeneous nucleation and growth of FePt NCs were allowed to take place at lower temperature (T ≈ 180–200°C); then, a thin polycrystalline Fe_xO_y shell was deposited onto the in situ generated FePt seeds upon prolonged heating of the reaction mixture at T ≈ 295°C. The shell rapidly dewetted out and evolved into a separate cubic spinel Fe₃O₄@γ-Fe₂O₃ core@shell domain attached aside, leaving a thin iron oxide shell on the diametrically opposite side of FePt (Nolle et al., 2009). Overall, this process permitted alleviating the intervening interfacial strain due to large difference (~8%) in lattice parameters between FePt and iron oxide (Erdemir et al., 2009; Nolle et al., 2009; Gentili et al., 2012; Thompson, 2012), albeit at the cost of nucleation of dislocations within the hetero-dimer lattice (Figuerola et al., 2008). Since each reaction step was selectively activated under distinct thermal conditions, regulation of both the temperature and the heating time guaranteed that the two material sections of the MHNCs formed at different stages of the synthesis course (Erdemir et al., 2009). As a consequence of the magnetic exchange coupling holding between the two soft and hard materials, the FePt–Fe_xO_y MHNCs exhibited tunable single-phase-like magnetic behavior and superior performance as MRI contrast agents, not otherwise achievable by their individual components (Figuerola et al., 2008; Nolle et al., 2009).

In a later report, OLAM-driven thermal reduction of rhodium acetate and decomposition of iron acetylacetonate were accomplished in consecutive heating steps at 200°C and 300°C, respectively, to synthesize asymmetric peanut-shaped Rh–Fe₃O₄ hetero-dimer MHNCs in OLAM/OLAC media (Jang et al., 2011b). In these heterostructures, the tiny Rh domain exhibited excellent iron-oxide-promoted catalytic activities for the selective reduction of nitroarenes and alkenes, while the larger supporting iron oxide allowed facile magnetic recyclability.