From Multi- to Single-Hollow Trimetallic Nanocrystals by Ultrafast Heating.

Metal nanocrystals (NCs) display unique physicochemical features that are highly dependent on nanoparticle dimensions, anisotropy, structure, and composition. The development of synthesis methodologies that allow us to tune such parameters finely emerges as crucial for the application of metal NCs in catalysis, optical materials, or biomedicine. Here, we describe a synthetic methodology to fabricate hollow multimetallic heterostructures using a combination of seed-mediated growth routes and femtosecond-pulsed laser irradiation. The envisaged methodology relies on the coreduction of Ag and Pd ions on gold nanorods (Au NRs) to form Au@PdAg core-shell nanostructures containing small cavities at the Au-PdAg interface. The excitation of Au@PdAg NRs with low fluence femtosecond pulses was employed to induce the coalescence and growth of large cavities, forming multihollow anisotropic Au@PdAg nanostructures. Moreover, single-hollow alloy AuPdAg could be achieved in high yield by increasing the irradiation energy. Advanced electron microscopy techniques, energy-dispersive X-ray spectroscopy (EDX) tomography, X-ray absorption near-edge structure (XANES) spectroscopy, and finite differences in the time domain (FDTD) simulations allowed us to characterize the morphology, structure, and elemental distribution of the irradiated NCs in detail. The ability of the reported synthesis route to fabricate multimetallic NCs with unprecedented hollow nanostructures offers attractive prospects for the fabrication of tailored high-entropy alloy nanoparticles.

Effectiveness of Gold Nanorods of Different Sizes in Photothermal Therapy to Eliminate Melanoma and Glioblastoma Cells.

Gold nanorods are the most commonly used nanoparticles in photothermal therapy for cancer treatment due to their high efficiency in converting light into heat. This study aimed to investigate the efficacy of gold nanorods of different sizes (large and small) in eliminating two types of cancer cell: melanoma and glioblastoma cells. After establishing the optimal concentration of nanoparticles and determining the appropriate time and power of laser irradiation, photothermal therapy was applied to melanoma and glioblastoma cells, resulting in the highly efficient elimination of both cell types. The efficiency of the PTT was evaluated using several methods, including biochemical analysis, fluorescence microscopy, and flow cytometry. The dehydrogenase activity, as well as calcein-propidium iodide and Annexin V staining, were employed to determine the cell viability and the type of cell death triggered by the PTT. The melanoma cells exhibited greater resistance to photothermal therapy, but this resistance was overcome by irradiating cells at physiological temperatures. Our findings revealed that the predominant cell-death pathway activated by the photothermal therapy mediated by gold nanorods was apoptosis. This is advantageous as the presence of apoptotic cells can stimulate antitumoral immunity in vivo. Considering the high efficacy of these gold nanorods in photothermal therapy, large nanoparticles could be useful for biofunctionalization purposes. Large nanorods offer a greater surface area for attaching biomolecules, thereby promoting high sensitivity and specificity in recognizing target cancer cells. Additionally, large nanoparticles could also be beneficial for theranostic applications, involving both therapy and diagnosis, due to their superior detection sensitivity.

Tunable gold nanorod/NAO conjugates for selective drug delivery in mitochondria-targeted cancer therapy.

Nonyl acridine orange (NAO) is a lipophilic and positively charged molecule widely used as a mitochondrial fluorescent probe. NAO is cytotoxic at micromolar concentration and might be potentially used as a mitochondria-targeted drug for cancer therapy. However, the use of NAO under in vivo conditions would be compromised by the unspecific interactions with off-target cells and negatively charged proteins present in the bloodstream. To tackle this limitation, we have synthesized NAO analogues carrying an imidazole group for their specific binding to nitrilotriacetic (NTA) functionalized gold nanorods (AuNRs). We demonstrate that AuNRs provide 104 binding sites and a controlled delivery under acidic conditions. Upon incubation with mouse embryonic fibroblasts, the endosomal acidic environment releases the NAO analogues from AuNRs, as visualized through the staining of the mitochondrial network. The addition of the monoclonal antibody Cetuximab to the conjugates enhanced their uptake within lung cancer cells and the conjugates were cytotoxic at subnanomolar concentrations (c50 ≈ 0.06 nM). Moreover, the specific interactions of Cetuximab with the epidermal growth factor receptor (EGFR) provided a specific targeting of EGFR-expressing lung cancer cells. After intravenous administration in patient-derived xenografts (PDX) mouse models, the conjugates reduced the progression of EGFR-positive tumors. Overall, the NAO-AuNRs provide a promising strategy to realize membrane mitochondria-targeted conjugates for lung cancer therapy.

Controlled pDNA Release in Gemini Cationic Lipoplexes by Femtosecond Laser Irradiation of Gold Nanostars.

The design of nanovectors able to overcome biological barriers is one of the main challenges in biomedicine. Gemini cationic lipids are considered potential candidates for gene therapy due to their high biocompatibility and capacity to condense nucleic acids safely in the form of lipoplexes. However, this approach presents difficulties regarding genetic unpacking and, therefore, control over this process becomes crucial to ensure successful transfection. In this work, gemini cationic lipoplexes were prepared in the presence of plasmonic gold nanostars (AuNSs) to afford a nanovector that efficiently releases plasmid DNA (pDNA) upon irradiation with near-infrared femtosecond laser pulses. A critical AuNSs concentration of 50 pM and optimized laser power density of 400 mW led to successful pDNA release, whose efficiency could be further improved by increasing the irradiation time. Agarose gel electrophoresis was used to confirm pDNA release. UV-Vis-NIR spectroscopy and transmission electron microscopy studies were performed to monitor changes in the morphology of the AuNSs and lipoplexes after irradiation. From a physicochemical point of view, this study demonstrates that the use of AuNSs combined with gemini cationic lipoplexes allows control over pDNA release under ultrafast laser irradiation.

Gemini Cationic Lipid-Type Nanovectors Suitable for the Transfection of Therapeutic Plasmid DNA Encoding for Pro-Inflammatory Cytokine Interleukin-12.

Ample evidence exists on the role of interleukin-12 (IL-12) in the response against many pathogens, as well as on its remarkable antitumor properties. However, the unexpected toxicity and disappointing results in some clinical trials are prompting the design of new strategies and/or vectors for IL-12 delivery. This study was conceived to further endorse the use of gemini cationic lipids (GCLs) in combination with zwitterionic helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphatidyl ethanol amine) as nanovectors for the insertion of plasmid DNA encoding for IL-12 (pCMV-IL12) into cells. Optimal GCL formulations previously reported by us were selected for IL-12-based biophysical experiments. In vitro studies demonstrated efficient pCMV-IL12 transfection by GCLs with comparable or superior cytokine levels than those obtained with commercial control Lipofectamine2000*. Furthermore, the nanovectors did not present significant toxicity, showing high cell viability values. The proteins adsorbed on the nanovector surface were found to be mostly lipoproteins and serum albumin, which are both beneficial to increase the blood circulation time. These outstanding results are accompanied by an initial physicochemical characterization to confirm DNA compaction and protection by the lipid mixture. Although further studies would be necessary, the present GCLs exhibit promising characteristics as candidates for pCMV-IL12 transfection in future in vivo applications.

Insights into colloidal nanoparticle-protein corona interactions for nanomedicine applications.

Colloidal nanoparticles (NPs) have attracted significant attention due to their unique physicochemical properties suitable for diagnosing and treating different human diseases. Nevertheless, the successful implementation of NPs in medicine demands a proper understanding of their interactions with the different proteins found in biological fluids. Once introduced into the body, NPs are covered by a protein corona (PC) that determines the biological behavior of the NPs. The formation of the PC can eventually favor the rapid clearance of the NPs from the body before fulfilling the desired objective or lead to increased cytotoxicity. The PC nature varies as a function of the different repulsive and attractive forces that govern the NP-protein interaction and their colloidal stability. This review focuses on the phenomenon of PC formation on NPs from a physicochemical perspective, aiming to provide a general overview of this critical process. Main issues related to NP toxicity and clearance from the body as a result of protein adsorption are covered, including the most promising strategies to control PC formation and, thereby, ensure the successful application of NPs in nanomedicine.

Protein Expression Knockdown in Cancer Cells Induced by a Gemini Cationic Lipid Nanovector with Histidine-Based Polar Heads.

A histidine-based gemini cationic lipid, which had already demonstrated its efficiency as a plasmid DNA (pDNA) nanocarrier, has been used in this work to transfect a small interfering RNA (siRNA) into cancer cells. In combination with the helper lipid monoolein glycerol (MOG), the cationic lipid was used as an antiGFP-siRNA nanovector in a multidisciplinary study. Initially, a biophysical characterization by zeta potential (ζ) and agarose gel electrophoresis experiments was performed to determine the lipid effective charge and confirm siRNA compaction. The lipoplexes formed were arranged in Lα lamellar lyotropic liquid crystal phases with a cluster-type morphology, as cryo-transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS) studies revealed. Additionally, in vitro experiments confirmed the high gene knockdown efficiency of the lipid-based nanovehicle as detected by flow cytometry (FC) and epifluorescence microscopy, even better than that of Lipofectamine2000*, the transfecting reagent commonly used as a positive control. Cytotoxicity assays indicated that the nanovector is non-toxic to cells. Finally, using nano-liquid chromatography tandem mass spectrometry (nanoLC-MS/MS), apolipoprotein A-I and A-II followed by serum albumin were identified as the proteins with higher affinity for the surface of the lipoplexes. This fact could be beyond the remarkable silencing activity of the histidine-based lipid nanocarrier herein presented.

3D Characterization and Plasmon Mapping of Gold Nanorods Welded by Femtosecond Laser Irradiation.

Ultrafast laser irradiation can induce morphological and structural changes in plasmonic nanoparticles. Gold nanorods (Au NRs), in particular, can be welded together upon irradiation with femtosecond laser pulses, leading to dimers and trimers through the formation of necks between individual nanorods. We used electron tomography to determine the 3D (atomic) structure at such necks for representative welding geometries and to characterize the induced defects. The spatial distribution of localized surface plasmon modes for different welding configurations was assessed by electron energy loss spectroscopy. Additionally, we were able to directly compare the plasmon line width of single-crystalline and welded Au NRs with single defects at the same resonance energy, thus making a direct link between the structural and plasmonic properties. In this manner, we show that the occurrence of (single) defects results in significant plasmon broadening.

Biocompatible Nanovector of siRNA Consisting of Arginine-Based Cationic Lipid for Gene Knockdown in Cancer Cells.

Despite the use of small interfering RNAs (siRNAs) as therapeutic agents through the knockdown expression of pathogenic proteins, transportation and delivery of such siRNAs into cells continue to be under investigation. Within nonviral vectors, cationic lipids that include amino acid residues in their structures, and that have already demonstrated their suitability as plasmid DNA nanocarriers, may be also considered as potential siRNA vehicles. A double-chain cationic lipid based on the amino acid arginine mixed with a helper lipid has been the object of this biophysical study. First, ζ-potential measurements and agarose gel electrophoresis experiments confirmed the siRNA compaction, while small-angle X-ray scattering analysis (SAXS) revealed the structural pattern of the lipoplexes. Two bicontinuous cubic phases were found to coexist: the double-gyroid phase (QIIG) and the double-diamond phase (QIID), with Pn3m and Ia3d as crystallographic space groups, respectively; the siRNA is known to be located inside their bicontinuous aqueous channels. Second, in vitro studies in HeLa-green fluorescent protein (GFP) and T731-GFP cell lines (modified for GFP overexpression) showed moderate to high gene knockdown levels (determined by flow cytometry and epifluorescence microscopy) with remarkable cell viabilities (CCK-8 assay). Finally, nano-liquid chromatography/mass spectrometry (nanoLC-MS/MS) was used to identify the nature of the proteins adhered to the surface of the lipoplexes after incubation with human serum, simulating their behavior in biological fluids. The abundant presence of lipoproteins and serum albumin in such protein corona, together with the coexistence of the bicontinuous cubic phases, may be behind the remarkable silencing activity of these lipoplexes. The results reported herein show that the use of amino-acid-based cationic lipids mixed with a suitable helper lipid, which have already provided good results as DNA plasmid nanocarriers in cellular transfection processes, may also be a biocompatible option, and so far little investigated, in gene silencing in vitro strategies.

Hollow Gold Nanoparticles Produced by Femtosecond Laser Irradiation.

Metallic hollow nanoparticles exhibit interesting optical properties that can be controlled by geometrical parameters. Irradiation with femtosecond laser pulses has emerged recently as a valuable tool for reshaping and size modification of plasmonic metal nanoparticles, thereby enabling the synthesis of nanostructures with unique morphologies. In this Letter, we use classical molecular dynamics simulations to investigate the solid-to-hollow conversion of gold nanoparticles upon femtosecond laser irradiation. Here, we suggest an efficient method for producing hollow nanoparticles under certain specific conditions, namely that the particles should be heated to a maximum temperature between 2500 and 3500 K, followed by a fast quenching to room temperature, with cooling rates lower than 120 ps. Therefore, we describe the experimental conditions for efficiently producing hollow nanoparticles, opening a broad range of possibilities for applications in key areas, such as energy storage and catalysis.

Micelle-directed chiral seeded growth on anisotropic gold nanocrystals.

Surfactant-assisted seeded growth of metal nanoparticles (NPs) can be engineered to produce anisotropic gold nanocrystals with high chiroptical activity through the templating effect of chiral micelles formed in the presence of dissymmetric cosurfactants. Mixed micelles adsorb on gold nanorods, forming quasihelical patterns that direct seeded growth into NPs with pronounced morphological and optical handedness. Sharp chiral wrinkles lead to chiral plasmon modes with high dissymmetry factors (~0.20). Through variation of the dimensions of chiral wrinkles, the chiroptical properties can be tuned within the visible and near-infrared electromagnetic spectrum. The micelle-directed mechanism allows extension to other systems, such as the seeded growth of chiral platinum shells on gold nanorods. This approach provides a reproducible, simple, and scalable method toward the fabrication of NPs with high chiral optical activity.

Au@Ag Core-Shell Nanorods Support Plasmonic Fano Resonances.

In this work, we investigated experimentally and theoretically the plasmonic Fano resonances (FRs) exhibited by core-shell nanorods composed of a gold core and a silver shell (Au@Ag NRs). The colloidal synthesis of these Au@Ag NRs produces nanostructures with rich plasmonic features, of which two different FRs are particularly interesting. The FR with spectral location at higher energies (3.7 eV) originates from the interaction between a plasmonic mode of the nanoparticle and the interband transitions of Au. In contrast, the tunable FR at lower energies (2.92-2.75 eV) is ascribed to the interaction between the dominant transversal LSPR mode of the Ag shell and the transversal plasmon mode of the Au@Ag nanostructure. The unique symmetrical morphology and FRs of these Au@Ag NRs make them promising candidates for plasmonic sensors and metamaterials components.

Intercellular Trafficking of Gold Nanostars in Uveal Melanoma Cells for Plasmonic Photothermal Therapy.

Efficient plasmonic photothermal therapies (PPTTs) using non-harmful pulse laser irradiation at the near-infrared (NIR) are a highly sought goal in nanomedicine. These therapies rely on the use of plasmonic nanostructures to kill cancer cells while minimizing the applied laser power density. Cancer cells have an unsettled capacity to uptake, retain, release, and re-uptake gold nanoparticles, thus offering enormous versatility for research. In this work, we have studied such cell capabilities for nanoparticle trafficking and its impact on the effect of photothermal treatments. As our model system, we chose uveal (eye) melanoma cells, since laser-assisted eye surgery is routinely used to treat glaucoma and cataracts, or vision correction in refractive surgery. As nanostructure, we selected gold nanostars (Au NSs) due to their high photothermal efficiency at the near-infrared (NIR) region of the electromagnetic spectrum. We first investigated the photothermal effect on the basis of the dilution of Au NSs induced by cell division. Using this approach, we obtained high PPTT efficiency after several cell division cycles at an initial low Au NS concentration (pM regime). Subsequently, we evaluated the photothermal effect on account of cell division upon mixing Au NS-loaded and non-loaded cells. Upon such mixing, we observed trafficking of Au NSs between loaded and non-loaded cells, thus achieving effective PPTT after several division cycles under low irradiation conditions (below the maximum permissible exposure threshold of skin). Our study reveals the ability of uveal melanoma cells to release and re-uptake Au NSs that maintain their plasmonic photothermal properties throughout several cell division cycles and re-uptake. This approach may be readily extrapolated to real tissue and even to treat in situ the eye tumor itself. We believe that our method can potentially be used as co-therapy to disperse plasmonic gold nanostructures across affected tissues, thus increasing the effectiveness of classic PPTT.

Formation of Hollow Gold Nanocrystals by Nanosecond Laser Irradiation.

The irradiation of spherical gold nanoparticles (AuNPs) with nanosecond laser pulses induces shape transformations yielding nanocrystals with an inner cavity. The concentration of the stabilizing surfactant, the use of moderate pulse fluences, and the size of the irradiated AuNPs determine the efficiency of the process and the nature of the void. Hollow nanocrystals are obtained when molecules from the surrounding medium (e.g., water and organic matter derived from the surfactant) are trapped during laser pulse irradiation. These experimental observations suggest the existence of a subtle balance between the heating and cooling processes experienced by the nanocrystals, which induce their expansion and subsequent recrystallization keeping exogenous matter inside. The described approach provides valuable insight into the mechanism of interaction of a pulsed nanosecond laser with AuNPs, along with interesting prospects for the development of hollow plasmonic nanoparticles with potential applications related to gas and liquid storage at the nanoscale.

A Non-Viral Plasmid DNA Delivery System Consisting on a Lysine-Derived Cationic Lipid Mixed with a Fusogenic Lipid.

The insertion of biocompatible amino acid moieties in non-viral gene nanocarriers is an attractive approach that has been recently gaining interest. In this work, a cationic lipid, consisting of a lysine-derived moiety linked to a C12 chain (LYCl) was combined with a common fusogenic helper lipid (DOPE) and evaluated as a potential vehicle to transfect two plasmid DNAs (encoding green fluorescent protein GFP and luciferase) into COS-7 cells. A multidisciplinary approach has been followed: (i) biophysical characterization based on zeta potential, gel electrophoresis, small-angle X-ray scattering (SAXS), and cryo-transmission electronic microscopy (cryo-TEM); (ii) biological studies by fluorescence assisted cell sorting (FACS), luminometry, and cytotoxicity experiments; and (iii) a computational study of the formation of lipid bilayers and their subsequent stabilization with DNA. The results indicate that LYCl/DOPE nanocarriers are capable of compacting the pDNAs and protecting them efficiently against DNase I degradation, by forming Lα lyotropic liquid crystal phases, with an average size of ~200 nm and low polydispersity that facilitate the cellular uptake process. The computational results confirmed that the LYCl/DOPE lipid bilayers are stable and also capable of stabilizing DNA fragments via lipoplex formation, with dimensions consistent with experimental values. The optimum formulations (found at 20% of LYCl content) were able to complete the transfection process efficiently and with high cell viabilities, even improving the outcomes of the positive control Lipo2000*.

pH-triggered endosomal escape of pore-forming Listeriolysin O toxin-coated gold nanoparticles.

BACKGROUND: A major bottleneck in drug delivery is the breakdown and degradation of the delivery system through the endosomal/lysosomal network of the host cell, hampering the correct delivery of the drug of interest. In nature, the bacterial pathogen Listeria monocytogenes has developed a strategy to secrete Listeriolysin O (LLO) toxin as a tool to escape the eukaryotic lysosomal system upon infection, allowing it to grow and proliferate unharmed inside the host cell. RESULTS: As a "proof of concept", we present here the use of purified His-LLO H311A mutant protein and its conjugation on the surface of gold nanoparticles to promote the lysosomal escape of 40 nm-sized nanoparticles in mouse embryonic fibroblasts. Surface immobilization of LLO was achieved after specific functionalization of the nanoparticles with nitrile acetic acid, enabling the specific binding of histidine-tagged proteins. CONCLUSIONS: Endosomal acidification leads to release of the LLO protein from the nanoparticle surface and its self-assembly into a 300 Å pore that perforates the endosomal/lysosomal membrane, enabling the escape of nanoparticles.

On the Large Near-Field Enhancement on Nanocolumnar Gold Substrates.

One of the most important and distinctive features of plasmonic nanostructures is their ability to confine large electromagnetic fields on nanometric volumes; i.e., the so-called hot spots. The generation, control and characterization of the hot spots are fundamental for several applications, like surface-enhanced spectroscopies. In this work, we characterize the near-field distribution and enhancement of nanostructured gold thin films fabricated by glancing angle deposition magnetron sputtering. These films are composed of columnar nanostructures with high roughness and high density of inter-columnar gaps, where the electromagnetic radiation can be confined, generating hot spots. As expected, the hot spots are localized in the gaps between adjacent nanocolumns and we use scattering-type scanning near-field optical microscopy to image their distribution over the surface of the samples. The experimental results are compared with finite-difference time-domain simulations, finding an excellent agreement between them. The spectral dependence of the field-enhancement is also studied with the simulations, together with surface-enhanced Raman spectroscopy at different excitation wavelengths in the visible-NIR range, proving a broad-band response of the substrates. These findings may result in interesting applications in the field of surface-enhanced optical spectroscopies or sensing.

Disconnecting Symmetry Breaking from Seeded Growth for the Reproducible Synthesis of High Quality Gold Nanorods.

One of the major difficulties hindering the widespread application of colloidal anisotropic plasmonic nanoparticles is the limited robustness and reproducibility of multistep synthetic methods. We demonstrate herein that the reproducibility and reliability of colloidal gold nanorod (AuNR) synthesis can be greatly improved by disconnecting the symmetry-breaking event from the seeded growth process. We have used a modified silver-assisted seeded growth method in the presence of the surfactant hexadecyltrimethylammonium bromide and n-decanol as a co-surfactant to prepare small AuNRs in high yield, which were then used as seeds for the growth of high quality AuNR colloids. Whereas the use of n-decanol provides a more-rigid micellar system, the growth on anisotropic seeds avoids sources of irreproducibility during the symmetry breaking step, yielding uniform AuNR colloids with narrow plasmon bands, ranging from 600 to 1270 nm, and allowing the fine-tuning of the final dimensions. This method provides a robust route for the preparation of high quality AuNR colloids with tunable morphology, size, and optical response in a reproducible and scalable manner.

Monodisperse Gold Nanorods for High-Pressure Refractive Index Sensing.

The effects of hydrostatic pressure on the surface plasmon resonances (SPRs) of aqueous dispersions of monodisperse gold nanorods (AuNRs) were determined up to 9 GPa. The ultranarrow longitudinal SPR band of monodisperse AuNRs allows us to monitor a gradual red shift with pressure, which shows abrupt jumps at the liquid to ice phase VI and ice phase VII transitions. Despite solidifying at low pressure (∼1.8 GPa), water displays a regime of quasi-hydrostaticity in said phases VI and VII, up to ca. 5 GPa. Above this pressure, nonhydrostatic effects manifest themselves through broadening of the SPR bands, but barely any effect is observed on the position of the surface plasmon mode. The variation in the SPR peak wavelength with pressure allowed us to determine the pressure dependence of the refractive index of water. Unlike Brillouin scattering or interferometric techniques, this plasmon-spectroscopy-based method leads to a more direct determination of the refractive index, which is well described empirically by Murnaghan-type equations in the three explored phases. We report herein the obtained analytical functions providing the pressure dependence of refractive index in the liquid, ice VI, and ice VII phases of water.

Facile Strategy for the Synthesis of Gold@Silica Hybrid Nanoparticles with Controlled Porosity and Janus Morphology.

Hybrid materials prepared by encapsulation of plasmonic nanoparticles in porous silica systems are of increasing interest due to their high chemical stability and applications in optics, catalysis and biological sensing. Particularly promising is the possibility of obtaining gold@silica nanoparticles (Au@SiO2 NPs) with Janus morphology, as the induced anisotropy can be further exploited to achieve selectivity and directionality in physical interactions and chemical reactivity. However, current methods to realise such systems rely on the use of complex procedures based on binary solvent mixtures and varying concentrations of precursors and reaction conditions, with reproducibility limited to specific Au@SiO2 NP types. Here, we report a simple one-pot protocol leading to controlled crystallinity, pore order, monodispersity, and position of gold nanoparticles (AuNPs) within mesoporous silica by the simple addition of a small amount of sodium silicate. Using a fully water-based strategy and constant content of synthetic precursors, cetyl trimethylammonium bromide (CTAB) and tetraethyl orthosilicate (TEOS), we prepared a series of four silica systems: (A) without added silicate, (B) with added silicate, (C) with AuNPs and without added silicate, and (D) with AuNPs and with added silicate. The obtained samples were characterised by transmission electron microscopy (TEM), small angle X-ray scattering (SAXS), and UV-visible spectroscopy, and kinetic studies were carried out by monitoring the growth of the silica samples at different stages of the reaction: 1, 10, 15, 30 and 120 min. The analysis shows that the addition of sodium silicate in system B induces slower MCM-41 nanoparticle (MCM-41 NP) growth, with consequent higher crystallinity and better-defined hexagonal columnar porosity than those in system A. When the synthesis was carried out in the presence of CTAB-capped AuNPs, two different outcomes were obtained: without added silicate, isotropic mesoporous silica with AuNPs located at the centre and radial pore order (C), whereas the addition of silicate produced Janus-type Au@SiO2 NPs (D) in the form of MCM-41 and AuNPs positioned at the silica⁻water interface. Our method was nicely reproducible with gold nanospheres of different sizes (10, 30, and 68 nm diameter) and gold nanorods (55 × 19 nm), proving to be the simplest and most versatile method to date for the realisation of Janus-type systems based on MCM-41-coated plasmonic nanoparticles.