Background

Translational barriers for FDA approval such as in vivo stability, localization in the body and cancer cells, and in vivo toxicity still exist. To overcome these barriers, researchers need to have access to platforms that incorporate naturally biocompatible ligands and can be used with imaging agents that are clinically accepted. In addition, new therapeutics that incorporate nanoparticles as the drug require high specificity and selectivity. These nanoparticles meet both of these needs with high stability and compatibility with antibodies for targeting, creating a targeted nano‑delivery system with high in vivo stability to reduce accumulation outside the target tissues.

Technology Overview

Hybrid bilayer membrane-coated nanoparticles for use as robust, stable, and targeted‑ready platform that can be used as drug delivery agents and imaging agents (). Although lipid-coated AuNPs are used in biomedical applications, hybrid bilayer membrane-coated nanoparticle systems are novel and provide lifetime and stability benefits over traditional lipid-based nanoparticles, enabling researchers and drug companies to develop diagnostics and treatments that take advantage of the natural biocompatibility and protected AuNPs to enable less in vivo toxicity and more payload delivery to the target tissues.

To demonstrate the membrane is anchored to the nanoparticle surface and that there is complete surface coverage, PSU performed a well-known cyanide (CN-) etch test with our gold nanoparticles (AuNPs).

Addition of cyanide (CN-) to hybrid lipid-coated AuNP showed nochange in the O.D. or LSPR characteristic of AuNPs () in the UV-Vis spectra. WithoutPSU’s addition of thiol, these nanoparticles decompose within minutes of CN-addition. This is proof that the gold surface is completely covered by lipids in a tight packing arrangement of the membrane such that CN-ions are unable to penetrate through the bilayer to etch the gold surface. Even in the presence of surfactants or membrane destabilizing molecules, such as TWEEN 20, CHAPS, and Triton X-100, no change is observed indicating the surfactants are unable to disrupt the hybrid membranes, enabling long-lived, stable particles suitable for next-generation diagnostic and drug research.

Benefits

This technology provides new and more stable and effective nanoparticles for areas such as image-guided drug delivery (IGDD). In addition to providing unique geometric characteristics that enable optimized optical qualities for imaging, PSU’s protected nanoparticles create long lived, stable nanoparticle cores with an exterior that can be easily modified for targeted delivery.

The three-dimensional nanoparticle support closely simulates physiological plasma membranes such as regions of local curvature that have the opportunity to influence nanoparticle uptake readily into cells.
Metal nanoparticles are customizable so their shape, size, and composition can be varied to tune their optical and electronic properties for use as contrast agents (X-ray CT, MRI, and OCT) and photothermal therapy.
The membrane composition can be adjusted to incorporate fluorescent dyes for bimodal imaging, targeting agents that recognize and enhance cellular uptake, or therapeutic drugs. These IGDD agents have built-in features within the same design to increase their robustness, to give them “stealth-like” character to bypass the immune system, to enhance cell recognition, and distribution of the contrast agents to visualize drug delivery as well as tumor response.
Unlike liposomes, which are prone to membrane rearrangement, these supported hybrid membranes significantly improve the structural stability of the membranes when anchored onto the gold surface to produce stable membranes that do not rearrange unlike micelles and liposomes.
Gold surface is completely covered by lipids in a tight packing arrangement and even cyanide can’t penetrate the bilayer to etch the gold surface. In addition the hybrids are stable in the presence of CN-for months.
Control membrane rearrangement to provide more stable and robust lipid-coated AuNPs shielded form surface oxidation, instability, and potential interactions with biomolecules.

Applications

IGDD applications, biomedical applications for use as therapeutics, prosthetics, drug delivery, and cellular labelling and imaging. Possible uses also in nanoparticle ink printing and antimicrobial agents.

Opportunity

This technology has a PCT application in place (WO/2017/156441). Portland State University look forward to doing further development work (i.e. specific optical properties or specialize coatings) with partner companies as well as licensing directly. The researcher is also willing to provide some guidance for development of the technology as an exploratory product for sale to research labs and pharmaceutical companies, to be manufactured under license.

Hybrid Lipid-coated Nanomaterials for Drug Delivery and Imaging

Patents

IP Status

Seeking