Dual-Function Nanoscale Coordination Polymer Nanoparticles for Targeted Diagnosis and Therapeutic Delivery in Atherosclerosis.

Atherosclerosis is the primary cause of cardiovascular events such as heart attacks and strokes. However, current medical practice lacks non-invasive, reliable approaches for both imaging atherosclerotic plaques and delivering therapeutic agents directly therein. Here, a biocompatible and biodegradable pH-responsive nanoscale coordination polymers (NCPs) based theranostic system is reported for managing atherosclerosis.

Impact of Joint Laxity on 2-Year KOOS Outcomes of Posterior Stabilized Total Knee Arthroplasty.

The objective of this study was to determine relationships between intraoperative posterior cruciate ligament (PCL) sacrificing posterior stabilized (PS) total knee arthroplasty (TKA) laxity measurements throughout flexion and patient outcomes at 2 years post-TKA and to define clinically relevant laxity thresholds to optimize patient outcomes.In a single-surgeon study, PCL sacrificing TKA using a robotics-assisted platform with a digital joint tensioning device was performed in 115 knees in 115 patients. Final intraoperative joint laxity was recorded, and 2-year Knee Injury and Osteoarthritis Outcome Scores (KOOSs) were obtained.

PDADMAC/Alginate-Coated Gold Nanorod For Eradication of Staphylococcus Aureus Biofilms.

Introduction: Over 75% of clinical microbiological infections are caused by bacterial biofilms that grow on wounds or implantable medical devices. This work describes the development of a new poly(diallyldimethylammonium chloride) (PDADMAC)/alginate-coated gold nanorod (GNR/Alg/PDADMAC) that effectively disintegrates the biofilms of (), a prominent pathogen responsible for hospital-acquired infections.

Methods: GNR was synthesised via seed-mediated growth method, and the resulting nanoparticles were coated first with Alg and then PDADMAC.

Conjugation with gold nanoparticles improves the stability of the KT2 peptide and maintains its anticancer properties.

One of the major weaknesses of therapeutic peptides is their sensitivity to degradation by proteolytic enzymes . Gold nanoparticles (GNPs) are a good carrier for therapeutic peptides to improve their stability and cellular uptake and . We conjugated the anticancer KT2 peptide as an anticancer peptide model to PEGylated GNPs (GNPs-PEG) and investigated the peptide stability, cellular uptake and ability of the GNPs-KT2-PEG conjugates to induce MDA-MB-231 human breast cancer cell death.

Conjugation of Peptides to Gold Nanoparticles.

Peptides and proteins have played an important role in many biological processes, functioning as enzymes, hormones, ligands, receptors, cell mediators, and structural components of cells. Being intrinsic molecules in signaling pathways, peptides allow for therapeutic intervention that closely mimic natural signaling cascades. However, the short chain of amino acids in free peptides is susceptible to proteolysis in vivo.

Stealthiness and Hematocompatibility of Gold Nanoparticles with Pre-Formed Protein Corona.

Studies have established that a serum protein corona pre-formed around gold nanorods (NRs) could be exploited for loading photosensitizers and chemotherapeutics to result in efficient cell kill with an extremely low dose. In this study, we further demonstrated that pre-forming a serum protein corona (PC) around citrate-capped NRs (NR-Cit) to form NR-PC conferred them stealth property and high hematocompatibility similar to the common strategy of PEGylating NRs, which would otherwise not be able to evade the immune system. Specifically, the NR-PC caused minimal complement activation with significantly lower formation of the terminal complement complex SC5b-9 measured in human serum containing NR-PC, and this resulted in low uptake by phagocytic U937 monocytes of 5.

In situ measurements of intracellular thermal conductivity using heater-thermometer hybrid diamond nanosensors.

Understanding heat dissipation processes at nanoscale during cellular thermogenesis is essential to clarify the relationships between the heat and biological processes in cells and organisms. A key parameter determining the heat flux inside a cell is the local thermal conductivity, a factor poorly investigated both experimentally and theoretically. Here, using a nanoheater/nanothermometer hybrid made of a polydopamine encapsulating a fluorescent nanodiamond, we measured the intracellular thermal conductivities of HeLa and MCF-7 cells with a spatial resolution of about 200 nm.

Dynamics of Human Serum Albumin Corona Formation on Gold Nanorods with Different Surface Ligands In Silico.

The interaction between human serum albumin (HSA) and nanoparticles (NPs) to form HSA corona has widely been studied since endogenous functions of albumin are highly attractive for drug delivery. However, a full understanding of the molecular dynamics and factors behind the formation of HSA corona, including interactions between HSA and different surface ligands and between neighboring HSA molecules, resulting in conformational change of HSA is presently lacking. Here, we assembled 14 HSA molecules around gold nanorods (AuNRs) with different surface chemistries (bare gold surface, cetyltrimethylammonium bromide (CTAB), polystyrene sulfonate (PSS), and polydiallyldimethylammonium chloride (PDADMAC)) in silico and examined the dynamics of HSA corona formation using coarse-grained molecular dynamics for 300 ns of simulation.

Innate immune activation by conditioned medium of cancer cells following combined phototherapy with photosensitizer-loaded gold nanorods.

Nanoparticle-based phototherapy has evolved to include immunotherapy as an effective treatment combination for cancers through inducing anti-cancer immune activation leading to downstream adaptive responses and immune protection. However, most cancer phototherapy studies that claimed anti-cancer immunogenic effects often included exogenous immunostimulants to potentiate immune responses and did not clearly establish their effects on immune cells. In this study, we showed that combined photodynamic (PDT) and photothermal therapy (PTT) using gold nanorods (NRs) loaded with the photosensitizer chlorin e6 (Ce6) on endogenously formed mouse serum (MS) protein coronas (i.

Polyelectrolyte stiffness on gold nanorods mediates cell membrane damage.

Charge and surface chemistry of gold nanorods (AuNRs) are often considered the predictive factors for cell membrane damage. Unfortunately, extensive research on AuNR passivated with polyelectrolyte (PE) ligand shell (AuNR-PE) has hitherto left a vital knowledge gap between the mechanical stability of the ligand shell and the cytotoxicity of AuNR-PEs. Here, the agreement between unbiased coarse-grained molecular dynamics (CGMD) simulation and empirical outcomes on hemolysis of red blood cells by AuNR-PEs demonstrates for the first time, a direct impact of the mechanical stability of the PE shell passivating the AuNRs on the lipid membrane rupture.

Rapid Detection of Carbapenemase-Producing Enterobacteriacae Based on Surface-Enhanced Raman Spectroscopy with Gold Nanostars.

The emergence and rapid spread of antibiotic resistance poses a serious threat to healthcare systems across the globe. The existence of carbapenemase-producing Enterobacteriaceae (CPE) such as renders the use of carbapenems, the last-resort class of β-lactam antibiotics, ineffective against bacterial infections, often leading to CPE-associated mortalities. Current methods of detection such as the Carba NP test and modified Hodge's test require hours to days to detect, which delays the response to isolate patients for rapid intervention.

Mannitol-induced gold nanoparticle aggregation for the ligand-free detection of viral particles.

Traditional virus detection methods require ligands that bind to either viral capsid proteins or viral nucleic acids. Ligands are typically antibodies or oligonucleotides and they are expensive, have limited chemical stability, and can only detect one specific type of virus at a time. Here, the biochemical surface properties of viruses are exploited for ligand-free, nonspecific virus detection.

Mucopenetration and biocompatibility of polydopamine surfaces for delivery in an Ex Vivo porcine bladder.

Urine voiding and the presence of a mucus layer on the apical surface of the urothelium are two major challenges towards an effective intravesical drug delivery for bladder malignancies. Improved bioavailability to the underlying bladder tissue could be achieved with delivery vectors that diffuse efficiently through the bladder mucus. Pegylation of delivery vectors remains the existing "gold standard" to enhance mucosal delivery despite known poor cell uptake and reported PEG sensitivity.

Enhanced Secretion of Functional Insulin with DNA-Functionalized Gold Nanoparticles in Cells.

We have previously shown the use of gold nanoparticles (AuNPs) functionalized with DNA (AuNP-DNA) to increase insulin mRNA translation in a cell-free system. In this study, we translate the concept into a whole cell system to demonstrate functionality despite the additional complexity of intracellular delivery and mRNA translation inside living cells. We selected an insulin-secreting pancreatic islet cell line, RIN-5F, as our model and designed a DNA oligomer (insDNA) that is complementary to the 3'-untranslated region of insulin mRNA for conjugation to AuNPs (AuNP-insDNA).

Exploiting Protein Corona around Gold Nanoparticles Conjugated to p53 Activating Peptides To Increase the Level of Stable p53 Proteins in Cells.

Therapeutic peptides suffer from major drawbacks such as peptide degradation in vivo due to proteolysis. Gold nanoparticles (AuNPs) are an effective carrier for therapeutic peptides that improve their stability in vivo, while also enabling nonspecific adsorption of complementary proteins to enhance their effectiveness. Using p53 peptide as a model known to disrupt the intracellular MDM2-p53 protein-protein interaction which tags the endogenous p53 proteins for degradation, we conjugated p53 peptides to AuNPs (AuNP-p53) and examined the functionality of AuNP-p53 to release the endogenous p53 proteins from being tagged for degradation, thereby increasing the level of stable p53 proteins in acute myeloid leukemia 2 (AML2) cells.

Polydopamine Coating Enhances Mucopenetration and Cell Uptake of Nanoparticles.

Mucus is an endogenous viscoelastic biopolymer barrier that limits the entry of foreign pathogens and therapeutic carriers to the underlying mucosal cells. This could be overcome with a hydrophilic and nonpositively charged carrier surface that minimizes interactions with the mucin glycoprotein fibers. Although PEGylation remains an attractive surface strategy to enhance mucopenetration, cell uptake of PEGylated nanoparticles (NPs) often remains poor.

Protein Corona Formed from Different Blood Plasma Proteins Affects the Colloidal Stability of Nanoparticles Differently.

Significant progress in the characterization of protein corona has been made. However, insights on how the corona affects the aggregation of nanoparticles (NPs) and consequent biological identity are still lacking. Here, we examined how the corona formed from four major serum proteins, immunoglobulin G (IgG), fibrinogen (FBG), apolipoprotein A1 (ApoA1), and human serum albumin (HSA), over a range of concentrations affects the aggregation of gold NPs (AuNPs).

Size-dependent neutralizing activity of gold nanoparticle-based subunit vaccine against dengue virus.

Unlabelled: Dengue results in substantial human morbidity and significant socio-economic impacts, but a specific dengue therapeutic is not available. The currently available dengue vaccine has low efficacy and high rate of adverse effects, necessitating different strategies for the development of a safer and more efficient vaccine against dengue virus. We describe here a hybrid combination of different-sized gold nanoparticles (AuNPs) and domain III of envelope glycoprotein derived from serotype 2 of dengue virus (EDIII) as dengue subunit vaccine.

Influence of protein corona and caveolae-mediated endocytosis on nanoparticle uptake and transcytosis.

Transcytosis of nanoparticles (NPs) is emerging as an attractive alternative to the paracellular route in cancer drug delivery with studies suggesting targeting caveolae-mediated endocytosis to maximize NP transcytosis. However, there are limited studies on transcytosis of NPs, especially for corona-coated NPs. Most studies focused on cellular uptake as an indirect measure of the NP's transcellular permeability (Pd).

Polydopamine Nanoparticles Enhance Drug Release for Combined Photodynamic and Photothermal Therapy.

Our study shows a facile two-step method which does not require the use of core templates to load a hydrophobic photosensitizer drug chlorin e6 (Ce6) within polydopamine (PDA) nanoparticles (NPs) while maintaining the intrinsic surface properties of PDA NPs. This structure is significantly different from hollow nanocapsules which are less stiff as they do not possess a core. To our knowledge, there exist no similar studies in the literature on drug loading within the polymer matrix of PDA NPs.

Quantitative and Label-Free Detection of Protein Kinase A Activity Based on Surface-Enhanced Raman Spectroscopy with Gold Nanostars.

The activity of extracellular protein kinase A (PKA) is known to be a biomarker for cancer. However, conventional PKA assays based on colorimetric, radioactive, and fluorometric techniques suffer from intensive labeling-related preparations, background interference, photobleaching, and safety concerns. While surface-enhanced Raman spectroscopy (SERS)-based assays have been developed for various enzymes to address these limitations, their use in probing PKA activity is limited due to subtle changes in the Raman spectrum with phosphorylation.

Quantifying Vascular Distribution and Adhesion of Nanoparticles with Protein Corona in Microflow.

The protein corona has emerged as an important determinant of biological response in nanoparticle (NP) drug delivery. However, there is presently no reported study on how the protein corona affects the behavior of NPs in microflow and its subsequent interactions with the vascular endothelium, which could affect their delivery to the target tumor site regardless of its targeting mechanism. Furthermore, a consensus on the role of physical and surface characteristics of NPs in affecting the margination of NPs is lacking due to different methods of quantifying margination.

Correction: Complement activation by gold nanoparticles passivated with polyelectrolyte ligands.

[This corrects the article DOI: 10.1039/C7RA13325A.].

Complement Activation by PEGylated Gold Nanoparticles.

Gold nanoparticles (AuNPs) are widely used in biomedical applications, but much less is known about their immunological properties, particularly their interaction with the complement system, a key component of innate immunity serving as an indicator of their biocompatibility. Using a library of different-sized AuNPs (10, 20, 40, and 80 nm) passivated with polyethylene glycol (PEG) of different molecular weight ( M = 1, 2, 5, and 10 kDa), we demonstrated that citrate-capped AuNPs activated the whole complement system in a size-dependent manner, characterized by the formation of the end-point activation product, SC5b-9, in human serum. Although PEGylation of AuNPs mitigated, but did not abolish, the activation level, complement activation by PEGylated AuNPs was independent of both the core size of AuNPs and the molecular weight of PEG.

Complement activation by gold nanoparticles passivated with polyelectrolyte ligands.

Gold nanoparticles passivated by polyelectrolyte ligands are widely used to confer stability and biofunctionality. While nanoparticles and polyelectrolytes have been reported as activators, their ability to activate the complement system as hybrid polyelectrolyte-coated nanoparticles is poorly characterized. Here, we found that gold nanoparticles passivated by common polyelectrolytes activated the system differently.