skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: LipiSensors: Exploiting Lipid Nanoemulsions to Fabricate Ionophore-Based Nanosensors
Ionophore-based nanosensors (IBNS) are tools that enable quantification of analytes in complex chemical and biological systems. IBNS methodology is adopted from that of bulk optodes where an ion exchange event is converted to a change in optical output. While valuable, an important aspect for application is the ability to intentionally tune their size with simple approaches, and ensure that they contain compounds safe for application. Lipidots are a platform of size tunable lipid nanoemulsions with a hydrophobic lipid core typically used for imaging and drug delivery. Here, we present LipiSensors as size tunable IBNS by exploiting the Lipidot model as a hydrophobic structural support for the sensing moieties that are traditionally encased in plasticized PVC nanoparticles. The LipiSensors we demonstrate here are sensitive and selective for calcium, reversible, and have a lifetime of approximately one week. By changing the calcium sensing components inside the hydrophobic core of the LipiSensors to those sensitive for oxygen, they are also able to be used as ratiometric O2 sensitive nanosensors via a quenching-based mechanism. LipiSensors provide a versatile, general platform nanosensing with the ability to directly tune the size of the sensors while including biocompatible materials as the structural support by merging sensing approaches with the Lipidot platform.  more » « less
Award ID(s):
1944204
PAR ID:
10213934
Author(s) / Creator(s):
; ; ; ; ;
Date Published:
Journal Name:
Biosensors
Volume:
10
Issue:
9
ISSN:
2079-6374
Page Range / eLocation ID:
120
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Not AvaStimuli-responsive polypeptides offer unique advantages for biomedical applications due to their biocompatibility, degradability, and structural tunability. In this study, we report the synthesis of innovative redox-responsive polypeptide-based diblock copolymers consisting of functional disulfide-containing homocysteine derivatives and hydrophobic γ-benzyl-l-glutamate segments via sequential ring-opening polymerizations. The polymerization kinetics revealed that the polymerizations were well-controlled with living characteristics, resulting in diblock copolymers PHcy-b-PBLG with narrow molecular weight distributions. The resulting functional-hydrophobic diblock copolymers were further converted to a variety of pendant chains via thiol–disulfide exchange reactions, yielding amphiphilic polymers with tunable surface charges. These disulfide-linked materials readily self-assembled into nanoparticles in aqueous environments with hydrophobic PBLG forming the core and redox-sensitive PHcy forming the shell. The redox-responsive nanoparticles displayed a narrow size distribution, excellent colloidal stability, and excellent biocompatibility. The disulfide bonds within the polymer backbone confer redox sensitivity, allowing potential cleavage in reducing environments. Owing to their tunable surface functionality, redox-responsiveness, and biocompatibility, this platform provides a versatile route to engineer responsive nanostructures for biomedical applications, for example, positively charged nanoparticles toward nucleic acid delivery.ilable 
    more » « less
  2. Organelles feature characteristic lipid compositions that lead to differences in membrane properties. In cells, membrane ordering and fluidity are commonly measured using the solvatochromic dye Laurdan, whose fluorescence is sensitive to lipid packing. As a general lipophilic dye, Laurdan stains all hydrophobic environments in cells; therefore, it is challenging to characterize membrane properties in specific organelles or assess their responses to pharmacological treatments in intact cells. Here, we describe the synthesis and application of Laurdan-derived probes that read out the membrane packing of individual cellular organelles. The set of organelle-targeted Laurdans (OTL) localizes to the ER, mitochondria, lysosomes, and Golgi compartments with high specificity while retaining the spectral resolution needed to detect biological changes in membrane ordering. We show that ratiometric imaging with OTLs can resolve membrane heterogeneity within organelles as well as changes in lipid packing resulting from inhibition of trafficking or bioenergetic processes. We apply these probes to characterize organelle-specific responses to saturated lipid stress. While the ER and lysosomal membrane fluidity is sensitive to exogenous saturated fatty acids, that of mitochondrial membranes is protected. We then use differences in ER membrane fluidity to sort populations of cells based on their fatty acid diet, highlighting the ability of organelle-localized solvatochromic probes to distinguish between cells based on their metabolic state. These results expand the repertoire of targeted membrane probes and demonstrate their application in interrogating lipid dysregulation. 
    more » « less
  3. Abstract The unique properties of cationic nanogels, such as their hydrophilicity and high loading capacity, make them a promising platform as drug delivery agents, particularly for the delivery of hydrophilic biomolecules. Although several synthetic methods exist for cationic nanogels, polymerization in dispersed media is advantageous due to its ability to provide control over composition and high monomer conversion. However, polymer droplets typically suffer from a significant increase in size during polymerization due to the Ostwald ripening process. Herein, the preparation of cationic nanogels by atom transfer radical polymerization under inverse microemulsion conditions of a hydrophilic inimer that prevents monomer diffusion and hence limits droplets’ growth during polymerization is reported. Additionally, the surface functionality of the nanogels can be modulated by the application of hydrophobic reactive surfactants or by grafting hydrophilic shells to form core‐shell cationic nanogels. The synthesized cationic nanogels are biocompatible, internalized to HEK 293 cells, and have a high complexation ability for plasmid DNA. 
    more » « less
  4. Many outbreaks of emerging disease ( e.g. , avian influenza, SARS, MERS, Ebola, COVID-19) are caused by viruses. In addition to direct person-to-person transfer, the movement of these viruses through environmental matrices (water, air, and food) can further disease transmission. There is a pressing need for rapid and sensitive virus detection in environmental matrices. Nanomaterial-based sensors (nanosensors), which take advantage of the unique optical, electrical, or magnetic properties of nanomaterials, exhibit significant potential for environmental virus detection. Interactions between viruses and nanomaterials (or recognition agents on the nanomaterials) can induce detectable signals and provide rapid response times, high sensitivity, and high specificity. Facile and field-deployable operations can be envisioned due to the small size of the sensing elements. In this frontier review, we summarize virus transmission via environmental pathways and then comprehensively discuss recent applications of nanosensors to detect various viruses. This review provides guidelines for virus detection in the environment through the use of nanosensors as a tool to decrease environmental transmission of current and emerging diseases. 
    more » « less
  5. Abstract Cell organelles feature characteristic lipid compositions that lead to differences in membrane properties. In living cells, membrane ordering and fluidity are commonly measured using the solvatochromic dye Laurdan, whose fluorescence is sensitive to membrane packing. As a general lipophilic dye, Laurdan stains all hydrophobic environments in cells, so it is challenging to characterize membrane properties in specific organelles or assess their responses to pharmacological treatments in intact cells. Here, we describe the synthesis and application of Laurdan-derived probes that read out membrane packing of individual cellular organelles. The set of Organelle-targeted Laurdans (OTL) localizes to the ER, mitochondria, lysosomes and Golgi compartments with high specificity, while retaining the spectral resolution needed to detect biological changes in membrane packing. We show that ratiometric imaging with OTL can resolve membrane heterogeneity within organelles, as well as changes in membrane packing resulting from inhibition of lipid trafficking or bioenergetic processes. We apply these probes to characterize organelle-specific responses to saturated lipid stress. While ER and lysosomal membrane fluidity is sensitive to exogenous saturated fatty acids, that of mitochondrial membranes is protected. We then use differences in ER membrane fluidity to sort populations of cells based on their fatty acid diet, highlighting the ability of organelle-localized solvatochromic probes to distinguish between cells based on their metabolic state. These results expand the repertoire of targeted membrane probes and demonstrate their application to interrogating lipid dysregulation. 
    more » « less