Observation of Self‐Assembled Core–Shell Structures in Epitaxially Embedded TbErAs Nanoparticles

Self‐assembled core–shell structured rare‐earth nanoparticles (TbErAs) are observed in a III–V semiconductor host matrix (In_0.53Ga_0.47As) nominally lattice‐matched to InP, grown via molecular beam epitaxy. Atom probe tomography demonstrates that the TbErAs nanoparticles have a core–shell structure, as seen both in the tomographic atom‐by‐atom reconstruction and concentration profiles. A simple thermodynamic model is created to determine when it is energetically favorable to have core–shell structures; the results strongly agree with the observations.     

Shuttle‐Mediated Nanoparticle Delivery to the Blood–Brain Barrier

Many therapeutic drugs are excluded from entering the brain due to their lack of transport through the blood–brain barrier (BBB). The development of new strategies for enhancing drug delivery to the brain is of great importance in diagnostics and therapeutics of central nervous diseases. To overcome this problem, a viral fusion peptide (gH625) derived from the glycoprotein gH of Herpes simplex virus type 1 is developed, which possesses several advantages including high cell translocation potency, absence of toxicity of the peptide itself, and the feasibility as an efficient carrier for delivering therapeutics. Therefore, it is hypothesized that brain delivery of nanoparticles conjugated with gH625 should be efficiently enhanced. The surface of fluorescent aminated polystyrene nanoparticles (NPs) is functionalized with gH625 via a covalent binding procedure, and the NP uptake mechanism and permeation across in vitro BBB models are studied. At early incubation times, the uptake of NPs with gH625 by brain endothelial cells is greater than that of the NPs without the peptide, and their intracellular motion is mainly characterized by a random walk behavior. Most importantly, gH625 peptide decreases NP intracellular accumulation as large aggregates and enhances the NP BBB crossing. In summary, these results establish that surface functionalization with gH625 may change NP fate by providing a good strategy for the design of promising carriers to deliver drugs across the BBB for the treatment of brain diseases.     

Dotted Core–Shell Nanoparticles for T1‐Weighted MRI of Tumors

Gd‐based T ₁‐weighted contrast agents have dominated the magnetic resonance imaging (MRI) contrast agent market for decades. Nevertheless, they are reported to be nephrotoxic and the U.S. Food and Drug Administration has issued a general warning concerning their use. In order to reduce the risk of nephrotoxicity, the MRI performance of the Gd‐based T ₁‐weighted contrast agents needs to be improved to allow a much lower dosage. In this study, novel dotted core–shell nanoparticles (FeGd‐HN3‐RGD2) with superhigh r ₁ value (70.0 mM^?1 s^?1) and very low r ₂/r ₁ ratio (1.98) are developed for high‐contrast T ₁‐weighted MRI of tumors. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay and histological analyses show good biocompatibility of FeGd‐HN3‐RGD2. Laser scanning confocal microscopy images and flow cytometry demonstrate active targeting to integrin α_vβ₃ positive tumors. MRI of tumors shows high tumor ΔSNR for FeGd‐HN3‐RGD2 (477 ± 44%), which is about 6‐7‐fold higher than that of Magnevist (75 ± 11%). MRI and inductively coupled plasma results further confirm that the accumulation of FeGd‐HN3‐RGD2 in tumors is higher than liver and spleen due to the RGD2 targeting and small hydrodynamic particle size (8.5 nm), and FeGd‐HN3‐RGD2 is readily cleared from the body by renal excretion.     

Wide‐Range Tunable Fluorescence Lifetime and Ultrabright Luminescence of Eu‐Grafted Plasmonic Core–Shell Nanoparticles for Multiplexing

Wide‐range, well‐separated, and tunable lifetime nanocomposites with ultrabright fluorescence are highly desirable for applications in optical multiplexing such as multiplexed biological detection, data storage, and security printing. Here, a synthesis of tunable fluorescence lifetime nanocomposites is reported featuring europium chelate grafted onto the surface of plasmonic core–shell nanoparticles, and systematically investigated their optical performance. In a single red color emission channel, more than 12 distinct fluorescence lifetime populations with high fluorescence efficiency (up to 73%) are reported. The fluorescence lifetime of Eu‐grafted core–shell nanoparticles exhibits a wider tunable range, possesses larger lifetime interval and is more sensitive to separation distance than that of ordinary Eu‐doping core–shell type. These superior performances are attributed to the unique nanostructure of Eu‐grafed type. In addition, these as‐prepared nanocomposites are used for security printing to demonstrate optical multiplexing applications. The optical multiplexing experiments show an interesting pseudo‐information “a rabbit in a well” and conceal the real message “NKU.”     

Modular Metal–Organic Polyhedra Superassembly: From Molecular‐Level Design to Targeted Drug Delivery

Targeted drug delivery remains at the forefront of biomedical research but remains a challenge to date. Herein, the first superassembly of nanosized metal–organic polyhedra (MOP) and their biomimetic coatings of lipid bilayers are described to synergistically combine the advantages of micelles and supramolecular coordination cages for targeted drug delivery. The superassembly technique affords unique hydrophobic features that endow individual MOP to act as nanobuilding blocks and enable their superassembly into larger and well‐defined nanocarriers with homogeneous sizes over a broad range of diameters. Various cargos are controllably loaded into the MOP with high payloads, and the nanocages are then superassembled to form multidrug delivery systems. Additionally, functional nanoparticles are introduced into the superassemblies via a one‐pot process for versatile bioapplications. The MOP superassemblies are surface‐engineered with epidermal growth factor receptors and can be targeted to cancer cells. In vivo studies indicated the assemblies to have a substantial circulation half‐life of 5.6 h and to undergo renal clearance—characteristics needed for nanomedicines.     

Cationic Bovine Serum Albumin Based Self‐Assembled Nanoparticles as siRNA Delivery Vector for Treating Lung Metastatic Cancer

It is generally believed that intravenous application of cationic vectors is limited by the binding of abundant negatively charged serum components, which may cause rapid clearance of the therapeutic agent from the blood stream. However, previous studies show that systemic delivery of cationic gene vectors mediates specific and efficient transfection within the lung, mainly as a result of interaction of the vectors with serum proteins. Based on these findings, a novel and charge‐density‐controllable siRNA delivery system is developed to treat lung metastatic cancer by using cationic bovine serum albumin (CBSA) as the gene vector. By surface modification of BSA, CBSA with different isoelectric points (pI) is synthesized and the optimal cationization degree of CBSA is determined by considering the siRNA binding and delivery ability, as well as toxicity. The CBSA can form stable nanosized particles with siRNA and protect siRNA from degradation. CBSA also shows excellent abiliies to intracellularly deliver siRNA and mediate significant accumulation in the lung. When Bcl2‐specific siRNA is introduced to this system, CBSA/siRNA nanoparticles exhibit an efficient gene‐silencing effect that induces notable cancer cell apoptosis and subsequently inhibits the tumor growth in a B16 lung metastasis model. These results indicate that CBSA‐based self‐assembled nanoparticles can be a promising strategy for a siRNA delivery system for lung targeting and metastatic cancer therapy.     

Design of Bistable Gold@Spin‐Crossover Core–Shell Nanoparticles Showing Large Electrical Responses for the Spin Switching

A simple chemical protocol to prepare core–shell gold@spin‐crossover (Au@SCO) nanoparticles (NPs) based on the 1D spin‐crossover [Fe(Htrz)₂(trz)](BF₄) coordination polymer is reported. The synthesis relies on a two‐step approach consisting of a partial surface ligand substitution of the citrate‐stabilized Au NPs followed by the controlled growth of a very thin layer of the SCO polymer. As a result, colloidally stable core@shell spherical NPs with a Au core of ca. 12 nm and a thin SCO shell 4 nm thick, are obtained, exhibiting a narrow distribution in sizes. Differential scanning calorimetry proves that a cooperative spin transition in the range 340–360 K is maintained in these Au@SCO NPs, in full agreement with the values reported for pristine 4 nm SCO NPs. Temperature‐dependent charge‐transport measurements of an electrical device based on assemblies of these Au@SCO NPs also support this spin transition. Thus, a large change in conductance upon spin state switching, as compared with other memory devices based on the pristine SCO NPs, is detected. This results in a large improvement in the sensitivity of the device to the spin transition, with values for the ON/OFF ratio which are an order of magnitude better than the best ones obtained in previous SCO devices.     

Drug‐Loaded Multifunctional Nanoparticles Targeted to the Endocardial Layer of the Injured Heart Modulate Hypertrophic Signaling

Ischemic heart disease is the leading cause of death globally. Severe myocardial ischemia results in a massive loss of myocytes and acute myocardial infarction, the endocardium being the most vulnerable region. At present, current therapeutic lines only ameliorate modestly the quality of life of these patients. Here, an engineered nanocarrier is reported for targeted drug delivery into the endocardial layer of the left ventricle for cardiac repair. Biodegradable porous silicon (PSi) nanoparticles are functionalized with atrial natriuretic peptide (ANP), which is known to be expressed predominantly in the endocardium of the failing heart. The ANP–PSi nanoparticles exhibit improved colloidal stability and enhanced cellular interactions with cardiomyocytes and non‐myocytes with minimal toxicity. After confirmation of good retention of the radioisotope 111‐Indium in relevant physiological buffers over 4 h, in vivo single‐photon emission computed tomography (SPECT/CT) imaging and autoradiography demonstrate increased accumulation of ANP–PSi nanoparticles in the ischemic heart, particularly in the endocardial layer of the left ventricle. Moreover, ANP–PSi nanoparticles loaded with a novel cardioprotective small molecule attenuate hypertrophic signaling in the endocardium, demonstrating cardioprotective potential. These results provide unique insights into the development of nanotherapies targeted to the injured region of the myocardium.     

Porous Silicon Nanoparticle Delivery of Tandem Peptide Anti‐Infectives for the Treatment of Pseudomonas aeruginosa Lung Infections

There is an urgent need for new materials to treat bacterial infections. In order to improve antibacterial delivery, an anti‐infective nanomaterial is developed that utilizes two strategies for localization: i) a biodegradable nanoparticle carrier to localize therapeutics within the tissue, and ii) a novel tandem peptide cargo to localize payload to bacterial membranes. First, a library of antibacterial peptides is screened that combines a membrane‐localizing peptide with a toxic peptide cargo and discovers a tandem peptide that displays synergy between the two domains and is able to kill Pseudomonas aeruginosa at sub‐micromolar concentrations. To apply this material to the lung, the tandem peptide is loaded into porous silicon nanoparticles (pSiNPs). Charged peptide payloads are loaded into the pores of the pSiNP at ≈30% mass loading and ≈90% loading efficiency using phosphonate surface chemistry. When delivered to the lungs of mice, this anti‐infective nanomaterial exhibits improved safety profiles over free peptides. Moreover, treatment of a lung infection of P. aeruginosa results in a large reduction in bacterial numbers and markedly improves survival compared to untreated mice. Collectively, this study presents the selection of a bifunctional peptide‐based anti‐infective agent and its delivery via biodegradable nanoparticles for application to an animal model of lung infection.     

Securing the Payload,Finding the Cell,and Avoiding the Endosome: Peptide‐Targeted,Fusogenic Porous Silicon Nanoparticles for Delivery of siRNA

Despite the promise of ribonucleic acid interference therapeutics, the delivery of oligonucleotides selectively to diseased tissues in the body, and specifically to the cellular location in the tissues needed to provide optimal therapeutic outcome, remains a significant challenge. Here, key material properties and biological mechanisms for delivery of short interfering RNAs (siRNAs) to effectively silence target‐specific cells in vivo are identified. Using porous silicon nanoparticles as the siRNA host, tumor‐targeting peptides for selective tissue homing, and fusogenic lipid coatings to induce fusion with the plasma membrane, it is shown that the uptake mechanism can be engineered to be independent of common receptor‐mediated endocytosis pathways. Two examples of the potential broad clinical applicability of this concept in a mouse xenograft model of ovarian cancer peritoneal carcinomatosis are provided: silencing the Rev3l subunit of polymerase Pol ζ to impair DNA repair in combination with cisplatin; and reprogramming tumor‐associated macrophages into a proinflammatory state.