Fusogenic Liposomes for the Intracellular Delivery of Phosphocreatine.

Maintaining intracellular adenosine triphosphate (ATP) levels is essential for numerous cellular functions, including energy metabolism, muscle contraction, and nerve impulse transmission. ATP is primarily synthesized in mitochondria through oxidative phosphorylation. It is also generated in the cytosol under anaerobic conditions using phosphocreatine (PCr) as a phosphate donor to adenosine diphosphate.

Multivalent Display of Erythropoietin on Quantum Dots Enhances Aquaporin-4 Expression and Water Transport in Human Astrocytes .

In mammalian cells, growth factor-induced intracellular signaling and protein synthesis play a critical role in cellular physiology and homeostasis. In the brain's glymphatic system (GS), the water-conducting activity of aquaporin-4 (AQPN-4) membrane channels (expressed in polarized fashion on astrocyte end-feet) mediates the clearance of wastes through the convective transport of fluid and solutes through the perivascular space. The glycoprotein erythropoietin (EPO) has been shown to induce the astrocyte expression of AQPN-4 via signaling through the EPO receptor and the JAK/STAT signaling pathway.

Special Issue "Nanoparticle-Mediated Drug Delivery, Imaging, and Control of Cellular Functions".

Over the past several decades, nanoparticles (NPs) have shown promising capabilities in the field of medicine for their applications as vehicles for targeted drug delivery [...

Photothermal-Enhanced Modulation of Cellular Membrane Potential Using Long-Wavelength-Activated Gold Nanoflowers.

In mammalian cells, plasma membrane potential plays vital roles in both physiology and pathology and it is controlled by a network of membrane-resident ion channels. There is considerable interest in the use of nanoparticles (NPs) to control biological functions, including the modulation of membrane potential. The photoexcitation of gold NPs (AuNPs) tethered close to the plasma membrane has been shown to induce membrane depolarization via localized heating of the AuNP surface coupled with the opening of voltage-gated sodium channels.

Nanoparticle-based delivery of nitric oxide for therapeutic applications.

Nitric oxide (NO), a low molecular weight signaling molecule, plays critical roles in both cellular health and disease. There is continued interest in new modalities for the controlled therapeutic delivery of NO to cells and tissues. The physicochemical properties of NO (including its short half-life and on-demand synthesis at the point of function), however, pose considerable challenges for its specific and efficient delivery.

Cobalt(III)- and rhodium(III)-porphyrin complexes for the effective degradation of fentanyl: Biological inactivation and mechanistic insights.

Cobalt(III) and rhodium(III) complexes containing the water-soluble porphyrin ligand meso-tri(4-sulfonatophenyl)mono(4-carboxyphenyl)porphine (CSTPP), [Rh(CSTPP)]Na•nHO (1) and [Co(CSTPP)]Na•nHO (2) were prepared from the direct reaction of free porphyrin and metal chloride salts in refluxing MeOH/DMF or EtOH/HO. Compounds 1 and 2 were characterized using UV-vis and H NMR spectroscopies, and high-resolution mass spectrometry. Cell culture based assays of opioid receptor activation showed that while the rhodium complex reduced fentanyl opioid activity 113-fold to an IC50 value of 1.

Liquid Crystal Nanoparticle Conjugates for Scavenging Reactive Oxygen Species in Live Cells.

The elevated intracellular production of or extracellular exposure to reactive oxygen species (ROS) causes oxidative stress to cells, resulting in deleterious irreversible biomolecular reactions (e.g., lipid peroxidation) and disease progression.

Determining the Cytosolic Stability of Small DNA Nanostructures .

DNA nanostructures have proven potential in biomedicine. However, their intracellular interactions─especially cytosolic stability─remain mostly unknown and attempts to discern this are confounded by the complexities of endocytic uptake and entrapment. Here, we bypass the endocytic uptake and evaluate the DNA structural stability directly in live cells.

Sensing Nitric Oxide in Cells: Historical Technologies and Future Outlook.

Nitric oxide (NO) is a critical cell signaling molecule with important roles in both normal cellular physiology and pathology. Over the past 20 years, multiple sensing modalities have been developed for the intracellular synthesis (endogenous) and release (exogenous) of NO. In this review, we survey the historical progression of NO sensing platforms, highlight the current state of the art, and offer a forward-looking view of how we expect the field of NO sensing to develop in the context of recent advances in bio-nanotechnology and nanoscale cellular biosensors.

Recent Progress in Bioconjugation Strategies for Liposome-Mediated Drug Delivery.

In nanoparticle (NP)-mediated drug delivery, liposomes are the most widely used drug carrier, and the only NP system currently approved by the FDA for clinical use, owing to their advantageous physicochemical properties and excellent biocompatibility. Recent advances in liposome technology have been focused on bioconjugation strategies to improve drug loading, targeting, and overall efficacy. In this review, we highlight recent literature reports (covering the last five years) focused on bioconjugation strategies for the enhancement of liposome-mediated drug delivery.

Anionic Conjugated Polyelectrolytes for FRET-based Imaging of Cellular Membrane Potential.

We report a Förster resonance energy transfer (FRET)-based imaging ensemble for the visualization of membrane potential in living cells. A water-soluble poly(fluorene-cophenylene) conjugated polyelectrolyte (FsPFc10) serves as a FRET donor to a voltage-sensitive dye acceptor (FluoVolt ). We observe FRET between FsPFc10 and FluoVolt , where the enhancement in FRET-sensitized emission from FluoVolt is measured at various donor/acceptor ratios.

Nanoparticle-Mediated Visualization and Control of Cellular Membrane Potential: Strategies, Progress, and Remaining Issues.

The interfacing of nanoparticle (NP) materials with cells, tissues, and organisms for a range of applications including imaging, sensing, and drug delivery continues at a rampant pace. An emerging theme in this area is the use of NPs and nanostructured surfaces for the imaging and/or control of cellular membrane potential (MP). Given the important role that MP plays in cellular biology, both in normal physiology and in disease, new materials and methods are continually being developed to probe the activity of electrically excitable cells such as neurons and muscle cells.

Gold-Nanoparticle-Mediated Depolarization of Membrane Potential Is Dependent on Concentration and Tethering Distance from the Plasma Membrane.

The photoactivation of plasma-membrane-tethered gold nanoparticles (AuNPs) for the photothermally driven depolarization of membrane potential has recently emerged as a new platform for the controlled actuation of electrically active cells. In this report, we characterize the relationship between AuNP concentration and AuNP-membrane separation distance with the efficiency of photoactivated plasma membrane depolarization. We show in differentiated rat pheochromocytoma (PC-12) cells that AuNPs capped with poly(ethylene glycol) (PEG)-cholesterol ligands localize to the plasma membrane and remain resident for up to 1 h.

Active Cellular and Subcellular Targeting of Nanoparticles for Drug Delivery.

Nanoparticle (NP)-mediated drug delivery (NMDD) for active targeting of diseases is a primary goal of nanomedicine. NPs have much to offer in overcoming the limitations of traditional drug delivery approaches, including off-target drug toxicity and the need for the administration of repetitive doses. In the last decade, one of the main foci in NMDD has been the realization of NP-mediated drug formulations for active targeted delivery to diseased tissues, with an emphasis on cellular and subcellular targeting.

Nanoparticle-Peptide-Drug Bioconjugates for Unassisted Defeat of Multidrug Resistance in a Model Cancer Cell Line.

Multidrug resistance (MDR) is a significant challenge in the treatment of many types of cancers as membrane-associated transporters actively pump drugs out of the cell, limiting therapeutic efficacy. While nanoparticle (NP)-based therapeutics have emerged as a mechanism for overcoming MDR, they often rely on the delivery of multiple anticancer drugs, nucleic acid hybrids, or MDR pump inhibitors. The effectiveness of these strategies, however, can be limited by their off-target toxicity or the need for genetic transfection.

Cholesterol Functionalization of Gold Nanoparticles Enhances Photoactivation of Neural Activity.

Gold nanoparticles (AuNPs) attached to the extracellular leaflet of the plasma membrane of neurons can enable the generation of action potentials (APs) in response to brief pulses of light. Recently described techniques to stably bind AuNP bioconjugates directly to membrane proteins (ion channels) in neurons enable robust AP generation mediated by the photoexcited conjugate. However, a strategy that binds the AuNP to the plasma membrane in a non protein-specific manner could represent a simple, single-step means of establishing light-responsiveness in multiple types of excitable neurons contained in the same tissue.

Synthesis of a Reactive Oxygen Species-Responsive Doxorubicin Derivative.

A heterobifunctional reactive oxygen species (ROS)-responsive linker for directed drug assembly onto and delivery from a quantum dot (QD) nanoparticle carrier was synthesized and coupled to doxorubicin using -(3-dimethylaminopropyl)-'-ethylcarbodiimide hydrochloride (EDC)/sulfo⁻NHS coupling. The doxorubicin conjugate was characterized using ¹H NMR and LC-MS and subsequently reacted under conditions of ROS formation (Cu/H₂O₂) resulting in successful and rapid thioacetal oxidative cleavage, which was monitored using ¹H NMR.

Hybrid Liquid Crystal Nanocarriers for Enhanced Zinc Phthalocyanine-Mediated Photodynamic Therapy.

Current challenges in photodynamic therapy (PDT) include both the targeted delivery of the photosensitizer (PS) to the desired cellular location and the maintenance of PS efficacy. Zinc phthalocyanine (ZnPc), a macrocyclic porphyrin and a potent PS for PDT, undergoes photoexcitation to generate reactive singlet oxygen that kills cells efficiently, particularly when delivered to the plasma membrane. Like other commonly employed PS, ZnPc is highly hydrophobic and prone to self-aggregation in aqueous biological media.

The role of nanoparticles in the improvement of systemic anticancer drug delivery.

The systemic delivery of drugs to the body via circulation after oral administration is a preferred method of drug administration during cancer treatment given its ease of implementation. However, the physicochemical properties of many current anticancer drugs limit their effectiveness when delivered by systemic routes. The use of nanoparticles (NPs) has emerged as an effective means of overcoming the inherent limitations of systemic drug delivery.

A Quantum Dot-Protein Bioconjugate That Provides for Extracellular Control of Intracellular Drug Release.

The ability to control the intracellular release of drug cargos from nanobioconjugate delivery scaffolds is critical for the successful implementation of nanoparticle (NP)-mediated drug delivery. This is particularly true for hard NP carriers such as semiconductor quantum dots (QDs) and gold NPs. Here, we report the development of a QD-based multicomponent drug release system that, when delivered to the cytosol of mammalian cells, is triggered to release its drug cargo by the simple addition of a competitive ligand to the extracellular medium.

Cellular delivery of doxorubicin mediated by disulfide reduction of a peptide-dendrimer bioconjugate.

In this study, we developed a peptide-dendrimer-drug conjugate system for the pH-triggered direct cytosolic delivery of the cancer chemotherapeutic doxorubicin (DOX) using the pH Low Insertion Peptide (pHLIP). We synthesized a pHLIP-dendrimer-DOX conjugate in which a single copy of pHLIP displayed a generation three dendrimer bearing multiple copies of DOX via disulfide linkages. Biophysical analysis showed that both the dendrimer and a single DOX conjugate inserted into membrane bilayers in a pH-dependent manner.

Evaluating the potential of using quantum dots for monitoring electrical signals in neurons.

Success in the projects aimed at providing an advanced understanding of the brain is directly predicated on making critical advances in nanotechnology. This Perspective addresses the unique interface of neuroscience and nanomaterials by considering the foundational problem of sensing neuron membrane voltage and offers a potential solution that may be facilitated by a prototypical nanomaterial. Despite substantial improvements, the visualization of instantaneous voltage changes within individual neurons, whether in cell culture or in vivo, at both the single-cell and network level at high speed remains complex and problematic.

Utility of PEGylated dithiolane ligands for direct synthesis of water-soluble Au, Ag, Pt, Pd, Cu and AuPt nanoparticles.

Water soluble metallic nanoparticles are being developed for a variety of roles ranging from catalysis to drug delivery and as potential contrast agents. We demonstrate direct synthesis of high-quality water-soluble Au, Ag, Pt, Pd, Cu and alloyed AuPt nanoparticles as well as ligand-exchange of FePt, cubic Pt and Au/Pt core/shell nanoparticles using bidentate dithiolane PEG as a universal ligand. Simple chemistry can greatly expand the applications of metal nanoparticles.

Intracellularly Actuated Quantum Dot-Peptide-Doxorubicin Nanobioconjugates for Controlled Drug Delivery via the Endocytic Pathway.

Nanoparticle (NP)-mediated drug delivery (NMDD) has emerged as a novel method to overcome the limitations of traditional systemic delivery of therapeutics, including the controlled release of the NP-associated drug cargo. Currently, our most advanced understanding of how to control NP-associated cargos is in the context of soft nanoparticles (e.g.

Quantifying time-varying cellular secretions with local linear models.

Extracellular protein concentrations and gradients initiate a wide range of cellular responses, such as cell motility, growth, proliferation and death. Understanding inter-cellular communication requires spatio-temporal knowledge of these secreted factors and their causal relationship with cell phenotype. Techniques which can detect cellular secretions in real time are becoming more common but generalizable data analysis methodologies which can quantify concentration from these measurements are still lacking.