A Functionalized Hollow Mesoporous Silica Nanoparticles‐Based Controlled Dual‐Drug Delivery System for Improved Tumor Cell Cytotoxicity

Multifunctional nanoparticles for selectively targeting tumor cells and effectively delivering multiple drugs are urgently needed in cancer therapy. Here, a dual‐drug delivery system is prepared, based on functionalized hollow mesoporous silica nanoparticles (HMSNs). Doxorubicin (DOX) hydrochloride is loaded into the hollow core, and dichloro(1,2‐diaminocyclohexane)platinum (II) (DACHPt) is stored in the pores of the shell by the coordination interaction with the carboxyl groups modified on the pore walls, which also serves as barriers to control the DOX release. Detailed studies in vitro indicate that the DACHPt release is triggered by Cl^? through the cleavage of the coordination interaction, and the DOX release depends on the release rate of DACHPt and the environmental pH value. The surface of the mechanized nanoparticles is also modified by transferrin (Tf) to achieve the tumor specificity. Compared with individual drug delivery systems, the dual‐drug delivery system shows synergistic efficacy on the cell cytotoxicity (combination index = 0.30), resulting in improved tumor cell killing. The present dual‐drug delivery system provides a promising strategy to develop controlled and targeted combination therapies for efficient cancer treatment.     

Silica‐Coating of Hematite Nanoparticles Using Reactive Water‐Soluble Polyalkoxysiloxanes

In this article, we report on a new one‐step synthetic route to obtain multi‐functional silica‐coated hematite particles using a water‐based surfactant‐free technology. The synthesis and properties of uniform silica‐coated hematite particles with adjustable size, morphology, and silica shell thickness are discussed in detail. The developed method allows simultaneous formation of the silica shell around hematite core and incorporation of reactive groups on the surface of core–shell nanoparticles. Vinyl groups are introduced to the silica surface at once by pre‐functionalization of a water‐soluble hyperbranched polyalkoxysiloxanes with active double bonds. The reactivity of these surface‐immobilized vinyl groups is demonstrated by covalent attachment of rhodamine B using a thiol‐en click reaction.     

In Vitro Evaluation of Non‐Protein Adsorbing Breast Cancer Theranostics Based on 19F‐Polymer Containing Nanoparticles

Eight fluorinated nanoparticles (NPs) are synthesized, loaded with doxorubicin (DOX), and evaluated as theranostic delivery platforms to breast cancer cells. The multifunctional NPs are formed by self‐assembly of either linear or star‐shaped amphiphilic block copolymers, with fluorinated segments incorporated in the hydrophilic corona of the carrier. The sizes of the NPs confirm that small circular NPs are formed. The release kinetics data of the particles reveals clear hydrophobic core dependence, with longer sustained release from particles with larger hydrophobic cores, suggesting that the DOX release from these carriers can be tailored. Viability assays and flow cytometry evaluation of the ratios of apoptosis/necrosis indicate that the materials are non‐toxic to breast cancer cells before DOX loading; however, they are very efficient, similar to free DOX, at killing cancer cells after drug encapsulation. Both flow cytometry and confocal microscopy confirm the cellular uptake of NPs and DOX‐NPs into breast cancer cells, and in vitro ¹⁹F‐MRI measurement shows that the fluorinated NPs have strong imaging signals, qualifying them as a potential in vivo contrast agent for ¹⁹F‐MRI.     

Structural and Optical Properties of Gold/Silica “Mushroom” Particles Prepared by Interfacial Templating

Complex shaped nanoparticles featuring structural or surface chemical patchiness are of special interest in both fundamental and applied research areas. This study reports the preparation and optical properties of gold/silica “mushroom” nanoparticles, where a gold particle is only partially covered by the silica cap. The synthetic approach allows precise control over the particle structure. The interfacial preparation method relies on partially embedding the gold particles in a polystyrene layer that masks the immersed part of the gold particle during silica shell growth from an aqueous solution. By adjusting sacrificial polystyrene film thickness and silica growth time, precise control over the coverage and cap thickness can be achieved. Correlative electron microscopy and single particle scattering spectroscopy measurements underline the high precision and reproducibility of the method. The good agreement between the measured and simulated single particle spectra supported by near‐field calculations indicates that the observed changes in the dipolar plasmon resonance are influenced by the extent of coverage of the gold core by the silica cap. The straightforward methods readily available for gold and silica surface modification using range of different (bio)molecules make these well‐defined nanoscale objects excellent candidates to study fundamental processes of programmed self‐assembly or application as theranostic agents.     

Facile Preparation of Core-Shell Nanocomposite Microgels

Microgels with alginate (Alg) gel cores and shells of SiO₂ nanoparticles (so-called colloidosomes) were prepared by self-assembly of SiO₂ nanoparticles at ALG aqueous solution–hexane interfaces and subsequent in situ gelation caused by Ca²⁺ ions that were released from calcium-ethylenediamine tetraacetic acid chelate by decreasing the pH value through the slow hydrolysis of D-Gluconic-δ-lactone. The packing density of SiO₂ nanoparticles in the shell was about 0.906, indicating that the SiO₂ nanoparticles were present monolayer on the surfaces of the colloidosomes. The half release times of insulin microcrystals were 4 h for Alg gel microspheres and 10 h for Alg/SiO₂ colloidosomes at pH 7.4, compared to 1.5 h for bare insulin. The half release times of insulin microcrystals were 12 min for Alg gel microspheres and 30 min for Alg/SiO₂ colloidosomes at pH 1.2, compared to 30 s for bare insulin. The release rates of insulin from the colloidosomes with core–shell structure were slower than that from bare insulin crystals due to the dual barriers of the hydrogel cores and the close-packed inorganic shells. The release curves were nicely fitted by the Weibull equation and the release followed Fickian diffusion.     

Nanoscale Janus Particles with Dual Protein Functionalization

Biofunctionalized Janus particles with tailored surface chemistry are gathering interest for applications as catalysts, multifunctional cell surface targets, nanomotors, and drug delivery systems. The dual nature of the surface chemistry of Janus particles can be exploited to immobilize drugs, cell surface targets, and/or other functional molecules on both sides of the particle surface. In this study, a model system is established for the scalable preparation of nanoscale Janus particles with dual protein functionalization with the proteins ferritin and streptavidin. 80 nm silica nanoparticles (SiNPs) modified with azidosilane are used to prepare Pickering emulsions with molten wax as the droplet phase. The azide‐functionalized SiNPs on the Pickering emulsion droplets are further subjected to face‐selective silanization with biotin‐polyethylene glycol ethoxy silane. Afterward, ferritin is grafted on the azide‐functionalized side via a click‐reaction and the biotin groups are conjugated with streptavidin which is labeled with ultrasmall gold nanoparticles. In order to elucidate the advantages and limits of this approach, a detailed characterization is performed of the particles at every process step. The results show that this method represents a scalable platform for the versatile preparation of nanoscale Janus nanoparticles that can potentially be used with a wide variety of proteins.     

Metal Nanoparticle Coating of Oxide Nanospheres for Core‐Shell Structures

A low‐temperature route for coating oxide nanospheres with metal nanoparticles to achieve core‐shell structures is introduced. First results indicating a dense coverage of silica nanospheres of about 300 nm size with regularly arranged Ag and Au nanoparticles deposited by a modified incipient wetness impregnation procedure are presented. This synthesis works completely without external reducing agents or media, adhesive aids or functionalizing agents. Metal particles of only a few nanometers in size may serve as seeds for continuous metal coating of the oxide spheres by complementary processes. Structural characterization of the materials by transmission electron microscopy reveals a nearly spherical shape of the metal particles, the structure of which ranges from single crystalline to single twinned and multiply twinned configurations.     

Synthesis of core–shell nanoparticles with a Pt nanoparticle core and a silica shell

A method to prepare a core–shell structure consisting of a Pt metal core coated with a silica shell (Pt(in)SiO₂) is described herein. A silica shell was grown on poly(vinylpyrrolidone) (PVP)-stabilized Pt nanoparticles 2–3 nm in size through hydrolysis and condensation reactions of tetraethyl orthosilicate (TEOS) in a water/ethanol mixture with ammonia as a catalyst. This process requires precise control of the reaction conditions to avoid the formation of silica particles containing multiple Pt cores and core-free silica. The length of PVP molecules, water content, concentration of ammonia and Pt nanoparticles in solution were found to significantly influence the core–shell structure. By optimizing these parameters, it was possible to prepare core–shell particles each containing a single Pt nanoparticle with a silica layer coating approximately 10 nm thick.     

Poly‐L‐Arginine Grafted Silica Mesoporous Nanoparticles for Enhanced Cellular Uptake and their Application in DNA Delivery and Controlled Drug Release

Mesoporous silica nanoparticles (MSNs), that are capable of delivering gene and drugs to organisms in an effective and selective way have attracted much attention lately for its potential in the treatment of cancer. However, the successful application of MSNs for delivery of plasmid DNA or drugs requires surface modification of the silica with positively charged functional groups so that it binds to the negatively charged nucleic acids and also helps it penetrate through the cell membrane. We report for the first time the synthesis of a hybrid MSN where the cell penetrating cationic polypeptide poly‐L‐arginine synthesized by NCA polymerization is grafted onto the external surface of MSN using click chemistry. These poly‐L‐arginine grafted MSNs show low cytotoxity (85% cell viability at 100 μg/mL MSN concentration) and high cellular uptake by both HeLa and A549 (>90%). The poly‐L‐arginine grafted MSNs were used effectively to deliver mCherry DNA plasmid into cells leading to expression of the protein mCherry inside the cells (transfection efficiency 60%). In contrast, poly‐L‐arginine grafted non‐porous silica nanoparticles were unable to express the protein mCherry inside the cells although their uptake into the cells was as efficient as with poly‐L‐arginine grafted MSNs. We also show preliminary results to demonstrate that these hybrid MSNs can be used as a delivery vehicle for the anticancer drug Doxorubicin towards cancerous cells HeLa and A549. The biocompatibility of poly‐L‐arginine and its cell penetrating ability are expected to make these MSN conjugates very useful carriers for the delivery of genes and drugs into cancer cells.     

Polymeric‐Micelle‐Based Nanomedicine for siRNA Delivery

Small interfering RNAs (siRNAs) are a rapidly emerging class of innovative nucleic acid medicines for the treatment of diseases such as cancer. However, significant hurdles hamper their clinical application, including poor cellular uptake, instability under physiological conditions, off‐target effects, and possible immunogenicity. The development of suitable delivery systems that protect and efficiently transport siRNA to targeted cells has been pursued. Nanoparticle‐based vectors have been widely investigated as potential candidates for effective siRNA delivery. Among the different nanoparticles, polymeric micelles, which are self‐assembled nanoparticles composed of amphiphilic materials with a core‐shell structure, have attracted great attention in recent years. Polymeric micelles in the range of several tens to hundreds of nanometers can be prepared, regulated, and modified relatively easily. The outer hydrophilic segments can prolong the in vivo lifetime of siRNA to achieve effective accumulation in tumors and can also be modified with cationic charges that interact electrostatically with siRNA and be introduced with different moieties to target specific cells. The inner cores can improve the stability of micelles and serve as payloads for hydrophobic drugs. Here, the barriers impeding siRNA delivery, the different polymeric micelles of siRNA developed to date, their gene silencing or therapeutic activity, and advanced applications for the co‐delivery of drugs and siRNA by these delivery systems are reviewed.     

Liposomal Templating,Association with Mammalian Cells,and Cytotoxicity of Poly(vinyl alcohol) Physical Hydrogel Nanoparticles

The assembly, cellular internalization, and cytotoxicity of nanoparticles based on physical hydrogels of poly(vinyl alcohol) (PVA) are reported. PVA nanoparticles are assembled using a liposomal templating technique followed by removal of the lipids using isopropanol, a process that requires the presence of a custom‐made block copolymer, poly(vinyl alcohol‐b‐vinyl pyrrolidone), to avoid aggregation of the nanoparticles. Polymer hydrogelation is induced via incubation in aqueous isopropyl alcohol solution, which results in PVA hydrogel nanoparticles (PVA HNP) with excellent colloidal stability and stability towards disintegration over at least 24 h. Pristine PVA HNP are found to be remarkably stealth‐like and exhibit negligible cellular internalization. This feature is likely inherent with the low fouling nature of PVA and makes PVA HNP attractive for targeted drug delivery with a low level of association with non‐targeted cells and tissues. Blending PVA with varied amounts of collagen results in colloidal hydrogel particles with a well pronounced tendency towards association with mammalian cells, specifically hepatocytes and endothelial cells. The association of PVA HNP elicits minimal changes in cellular proliferation, making these novel hydrogel particles convenient tools for drug delivery applications and creation of implantable artificial organelles and sensors.     

Colloidal Core–Satellite Supraparticles via Preprogramed Burst of Nanostructured Micro‐Raspberry Particles

Colloidal molecules, or more general supraparticles, i.e., particles which are themselves assembled of smaller nanoparticles in a defined way, are known to be synthesizable via bottom‐up assembly techniques in colloidal dispersion. The amount of synthesizable particles is mostly limited to milligrams. Herein, a bottom‐up‐programed, triggerable top‐down process is reported to obtain core–satellite supraparticles, i.e., particles composed of a larger core particle surrounded by smaller satellite particles. The key is to prepare a nanostructured, microparticulate powder into which defined burst behavior is preprogramed. Once the system is mechanically triggered, it bursts into well‐defined nanosized core–satellite supraparticles. Scale‐up is easily feasible and several hundred grams per batch can be demonstrated. The product is a ready‐to‐use and flexibly processible powder. Upon simple mixing with a polymer, it disintegrates into the preprogramed core–satellite supraparticles, thus forming a highly sophisticated nanocomposite with the polymer matrix. A pure silica nanoparticle system and a silica–iron oxide nanoparticle hybrid system are presented to demonstrate the versatility of the approach. Enhanced mechanical and unexpected magneto‐optical properties with the particle system are found. The disintegration of the microparticles into individual core–satellite colloidal supraparticles is confirmed via in situ liquid cell transmission electron microscopy.     

Preparation of Photoluminescent Porous Silicon Nanoparticles by High‐Pressure Microfluidization

The use of high‐shear microfluidization as a rapid, reproducible, and high‐yield method to prepare nanoparticles of porous silicon (pSi) with a narrow size distribution is described. Porous films prepared by electrochemical etch of a single‐crystal silicon wafer are removed from the substrate, fragmented, dispersed in an aqueous solution, and then processed with a microfluidizer, which generates high yields (57%) of pSi nanoparticles of narrow size distribution (PDI = 0.263) without a filtration step. Preparation of pSi nanoparticles via microfluidization improves yields (by 2.4‐fold) and particle size uniformity (by 1.8‐fold), and it lowers the total processing time (by 36‐fold) over standard ultrasonication or ball milling methods. The average diameter of the nanoparticles can be adjusted over the range 150–350 nm by appropriate adjustment of processing steps. If the fluid carrier in the microfluidizer contains an oxidant for Si, the resulting pSi particles are prepared with a core–shell structure, in which an elemental Si core is encased in a silicon oxide shell. When an aqueous sodium tetraborate processing solution is used, microfluidization generates photoluminescent core–shell pSi particles with a quantum yield of 19% in a single step in less than 20 min.     

Self‐Assembled Binary Mixtures of Partially Etched Nanowires

Arrays of anisotropic particles are sought after for applications in optics, electronics, and energy. Structures assembled from multiple micro‐ or nanoparticles could incorporate the distinct properties of each component to achieve functions not possible from single‐population assemblies. In mixed‐particle populations, the assembly forces may differ between the particle types, which will in turn influence the final assembled structures. Here, binary particle mixtures are studied and compared to assemblies formed from each of the component particles alone. The particles are partially etched nanowires (PENs, ≈300 nm diameter, and 3–8 μm overall length), which are formed by the silica coating and subsequent etching of striped metal nanowires, such that what remains are silica nanotubes containing segments of metal core (Au, Pt, Rh, or Pt/Au) with controllable location and number, spaced by “empty” regions that fill with water. Binary mixtures of PENs with different core metals and segment patterns are examined here to explore how the different core segment material, length, position, and number affects overall self‐assembly behavior.     

A Multifunctional Nanocrystalline CaF2:Tm,Yb@mSiO2 System for Dual‐Triggered and Optically Monitored Doxorubicin Delivery

Daunting challenges in investigating the controlled release of drugs in complicated intracellular microenvironments demand the development of stimuli‐responsive drug delivery systems. Here, a nanoparticle system, CaF₂:Tm,Yb@mSiO₂, made of a mesoporous silica (mSiO₂) nanosphere with CaF₂:Tm,Yb upconversion nanoparticles (UCNPs) is developed, filling its mesopores and with its surface‐modified with polyacrylic acid for binding the anticancer drug molecules (doxorubicin, DOX). The unique design of CaF₂:Tm,Yb@mSiO₂ enables us to trigger the drug release by two mechanisms. One is the pH‐triggered mechanism, where drug molecules are preferentially released from the nanoparticles at acidic conditions unique for the intracellular environment of cancer cells compared to normal cells. Another is the 808 nm near infrared (NIR)‐triggered mechanism, where 808 nm NIR induces the heating of the nanoparticles to weaken the electrostatic interaction between drug molecules and nanoparticles. In addition, luminescence resonance energy transfer occurs from the UCNPs (the energy donor) to the DOX drug (the energy acceptor) in the presence of 980 nm NIR irradiation, allowing us to monitor the drug release by detecting the vanishing blue emission from the UCNPs. This study demonstrates a new multifunctional nanosystem for dual‐triggered and optically monitored drug delivery, which will facilitate the rational design of personalized cancer therapy.     

Silica encapsulation of luminescent silicon nanoparticles: stable and biocompatible nanohybrids

This article presents a process for surface coating and functionalization of luminescent silicon nanoparticles. The particles were coated with silica using a microemulsion process that was adapted to the fragile silicon nanoparticles. The as-produced core–shell particles have a mean diameter of 35 nm and exhibit the intrinsic photoluminescence of the silicon core. The silica layer protects the core from aqueous oxidation for several days, thus allowing the use of the nanoparticles for biological applications. The nanoparticles were further coated with amines and functionalized with polyethylene glycol chains and the toxicity of the particles has been evaluated at the different stages of the process. The core–shell nanoparticles exhibit no acute toxicity towards lung cells, which is promising for further development.     

Coaxial Electrospun Poly(L‐Lactic Acid) Ultrafine Fibers for Sustained Drug Delivery

A coaxial electrospinning technique to fabricate core‐shell ultrafine fiber mats for drug delivery application is described in this paper. Poly (L‐lactic acid) (PLLA) and tetracycline hydrochloride (TCH) were employed as the shell and core materials, respectively. To investigate the feasibility of the resulting fiber mats for use as drug release carriers, these electrospun fibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and tensile testing. In vitro drug release behavior was also examined by ultraviolet‐visible (UV‐VIS) spectroscopy. Results indicated that a reservoir‐type drug release device can be conveniently obtained through encapsulating TCH in the PLLA ultrafine fiber. The size of the ultrafine fibers had a significant effect on their physical‐chemical properties. Furthermore, a sustained TCH release from these fiber mats was also observed. Consequently, the electrospun ultrafine fiber mats containing drugs may be used as drug release carriers or made into biomedical devices such as sutures and wound dressings.     

Theranostic Iron@Gold Core–Shell Nanoparticles for Simultaneous Hyperthermia‐Chemotherapy upon Photo‐Stimulation

The challenges of nanoparticles, such as size‐dependent toxicity, nonbiocompatibility, or inability to undergo functionalization for drug conjugation, limit their biomedical application in more than one domain. Oval‐shaped iron@gold core–shell (oFe@Au) magnetic nanoparticles are engineered and their applications in magnetic resonance imaging (MRI), optical coherence tomography (OCT), and controlled drug release, are explored via photo stimulation‐generated hyperthermia. The oFe@Au nanoparticles have a size of 42.57 ± 5.99 nm and consist of 10.76 and 89.24 atomic % of Fe and Au, respectively. Upon photo‐stimulation for 10 and 15 minutes, the levels of cancer cell death induced by methotrexate‐conjugated oFe@Au nanoparticles are sixfold and fourfold higher, respectively, than oFe@Au nanoparticles alone. MRI and OCT confirm the application of these nanoparticles as a contrast agent. Finally, results of in vivo experiments reveal that the temperature is elevated by 13.2 °C, when oFe@Au nanoparticles are irradiated with a 167 mW cm^?2 808 nm laser, which results in a significant reduction in tumor volume and scab formation after 7 days, followed by complete disappearance after 14 days. The ability of these nanoparticles to generate heat upon photo‐stimulation also opens new doors for studying hyperthermia‐mediated controlled drug release for cancer therapy. Applications include biomedical engineering, cancer therapy, and theranostics fields.     

High quality and tuneable silica shell–magnetic core nanoparticles

Obtaining small (<50 nm), monodispersed, well-separated, single iron oxide core–silica (SiO₂) shell nanoparticles for biomedical applications is still a challenge. Preferably, they are synthesised by inverse microemulsion method. However, substantial amount of aggregated and multicore core–shell nanoparticles is the undesired outcome of the method. In this study, we report on the production of less than 50 nm overall size, monodispersed, free of necking, single core iron oxide–SiO₂ shell nanoparticles with tuneable shell thickness by a carefully optimized inverse microemulsion method. The high degree of control over the process is achieved by understanding the mechanism of core–shell nanoparticles formation. By varying the reaction time and precursor concentration, the thickness of silica layer on the core nanoparticles can be finely adjusted from 5 to 13 nm. Residual reactions during the workup were inhibited by a combination of pH control with shock freezing and ultracentrifuging. These high-quality tuneable core–shell nanocomposite particles exhibit superparamagnetic character and sufficiently high magnetization with great potential for biomedical applications (e.g. MRI, cell separation and magnetically driven drug delivery systems) either as-prepared or by additional surface modification for improved biocompatibility.     

Patchy colloidosomes – an emerging class of structures

A colloidosome, i.e., a selectively permeable capsule composed of colloidal particles forming a stable homogenous shell, is a tiny container that can be used for storage, transportation, and release of cargo species. There are many routes to preparing colloidosomes; dozens of examples of future applications of such colloidal capsules have been demonstrated. Their functionality can be further extended if the capsules are designed to have heterogeneous shells, i.e., one or more regions (patches) of a shell are composed of material with specific properties that differ from the rest of the shell. Such patchy colloidosomes, supplemented by functionalities similar to that offered by well-studied patchy particles, will surely possess advantageous properties when compared with their homogenous counterparts. For example, owing to specific interactions between patches, they either can self-assemble into complex structures; specifically adhere to a surface; release their cargo species in specific direction; or guided–align,–orient or –propel. Fabrication of patchy colloidal microcapsules has long been theorized by scientists able to design different models, but actual large-scale production remains a challenge. Until now, only a few methods for fabricating patchy colloidosomes have been demonstrated, and these include production by means of microfluidics and mechanical pipetting. The field of science related to fabrication and application of patchy colloidosomes is clearly unexplored, and we envision it blooming in the coming years.