Phage mimicking nanoparticles
Inventors
Nallathamby, Prakash Daniel • Hopf, Juliane
Assignees
Publication Number
US-12161725-B2
Publication Date
2024-12-10
Expiration Date
2039-11-07
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Abstract
An antibacterial nanoparticle (ANP) and related methods and antibacterial medical products are disclosed. An ANP includes a silica core with a plurality of gold nanospheres conjugated thereto and at least some of the gold nanospheres being silver-coated gold nanospheres. Iron oxide nanospheres may also be conjugated to the silica core, and at least some of the silver-coated gold nanospheres, or iron oxide nanospheres, if present, can be conjugated to one or more polycationic polymers and/or one or more antibacterial peptides.
Core Innovation
The invention discloses antibacterial nanoparticles (ANPs) that possess a silica core with a plurality of gold nanospheres conjugated or immobilized onto the core. At least some of these gold nanospheres are coated with a layer of silver, and iron oxide nanospheres may also be conjugated to the silica core. The nanoparticles structurally mimic the capsid structure and density distribution of protein turrets found on bacteriophages and are designed primarily to inhibit bacterial growth and, in some cases, kill pathogenic bacteria.
The background identifies the increasing occurrence of nosocomial infections caused by antibiotic-resistant bacteria and stagnation in the discovery of new antibiotics. Current nanomaterial-based antibacterial agents face limitations such as reduced efficacy due to bacterial efflux pumps and toxicity to eukaryotic cells. The patent addresses the urgent need for broad-spectrum antibacterial agents that are independent of antibiotics and effective in combating multidrug-resistant pathogens and preventing biofilm formation, especially in medical or clinical settings.
The ANPs may be further functionalized with polycationic polymers and/or antibacterial peptides, such as synthetic or naturally occurring antimicrobial peptides. The surface density of gold nanospheres or iron oxide nanospheres on the silica core is designed to closely resemble that of protein turrets on bacteriophages, enhancing the antibacterial properties of the nanoparticles. Additionally, modular design allows the anchoring of cell penetrating peptides, and fluorescein molecules can be attached for reporting or diagnostic purposes. The invention also encompasses related methods for producing these particles and provides antibacterial medical products containing such nanoparticles, including coatings for implants, surgical instruments, or topical creams.
Claims Coverage
The patent contains three independent claims, each defining a key inventive feature underlying the invention.
Antibacterial nanoparticle with silica core and silver-coated gold nanospheres
An antibacterial nanoparticle consisting of: - A silica core - A plurality of silver-coated gold nanospheres conjugated to the silica core - Optionally, a plurality of iron oxide nanospheres conjugated to the silica core - At least some of the silver-coated gold nanospheres or iron oxide nanospheres conjugated to one or more polycationic polymers and/or one or more antibacterial peptides
Antibacterial medical product comprising antibacterial nanoparticles
An antibacterial medical product comprising a plurality of the antibacterial nanoparticles as defined (with silica core, silver-coated gold nanospheres, optional iron oxide nanospheres, and optional conjugation to polycationic polymers or antibacterial peptides).
Method for creating an antibacterial nanoparticle
A method for creating an antibacterial nanoparticle comprising: 1. Immobilizing a plurality of gold nanospheres on a silica core 2. Coating at least a portion of the gold nanospheres with a layer of silver 3. Optionally, immobilizing a plurality of iron oxide nanospheres on the silica core 4. Conjugating one or more antibacterial peptides to the silver-coated gold nanospheres or to the iron oxide nanospheres, if any
These inventive features collectively define antibacterial nanoparticles that structurally mimic bacteriophage surfaces, methods for their creation, and the integration of such nanoparticles into medical products for broad-spectrum antibacterial applications.
Stated Advantages
Provides a broad-spectrum, antibiotic-free antibacterial agent effective against multidrug-resistant bacteria.
Structurally mimics bacteriophages to target bacterial membranes and disrupt bacterial cells while minimizing toxicity to eukaryotic tissue.
Exhibits high biocompatibility, being non-toxic (and in some cases growth-promoting) to human cells.
Can be modularly personalized and easily conjugated to other antimicrobial agents (peptides, polymers) to enhance antibacterial effectiveness.
Remains effective regardless of genomically-acquired antibiotic resistance, as antibacterial properties are not compromised by traditional resistance mechanisms.
Can be coated on medical or dental implants and surgical instruments to prevent bacterial colonization and biofilm formation.
Mode of action preserves bacterial DNA sequences, facilitating subsequent genetic analysis of resistant pathogens.
Documented Applications
Disposal or coating of antibacterial nanoparticles on permanent implants, temporary implants, dental implants, and surgical instruments to provide antibacterial or disinfectant effects and prevent adhesion or growth of biofilms.
Addition of antibacterial nanoparticles to a topological cream or ointment for treating bacterial infections by skin contact.
Integration of antibacterial nanoparticles into medical products to treat or prevent bacterial infections, including in pre-sterilized instrument kits.
Modular design enables use for diagnosing bacterial infections via fluorescein molecules released in response to bacterial enzymes.
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