Method of using laser-induced optoacoustics for the treatment of drug-resistant microbial infections
Inventors
Millenbaugh, Nancy • DeSilva, Mauris • Baskin, Jonathan • Elliot, William R.
Assignees
Publication Number
US-9993660-B2
Publication Date
2018-06-12
Expiration Date
2033-05-23
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Abstract
The present invention is related to novel functional antibody coated nanoparticles, and the preparation method thereof. The functional antibody coated nanoparticles according to the present invention can be used as photothermal agents to effectively inhibit the growth of microbes including drug-resistant strains and biofilm with laser irradiation.
Core Innovation
The invention relates to functional antibody coated nanoparticles that act as photothermal agents to inhibit the growth of microbes, including drug-resistant strains and biofilms, upon laser irradiation. These nanoparticles have a core capable of absorbing laser irradiation, such as metal nanoparticles or core-shell structures, and are coated with antimicrobial antibodies that specifically bind to target bacteria. The nanoparticles can be prepared by reacting a nanoparticle solution with an antibacterial antibody solution, allowing the antibody to be fixed on the nanoparticle surface using methods including covalent bonds, electrostatic interactions, or streptavidin-biotin bonds.
The invention addresses the challenge of multi-drug resistant bacterial infections that are increasingly difficult to treat with conventional antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA). Existing treatments like photodynamic therapy may be ineffective in hypoxic wound environments, and prior art methods requiring two antibodies to bind nanoparticles to bacteria have limited efficacy particularly against drug-resistant strains. This invention provides a simplified and effective non-antibiotic treatment by using functional antibody coated nanoparticles combined with laser irradiation to kill both methicillin-sensitive and resistant bacteria and to reduce or destroy biofilms.
Claims Coverage
The patent contains one independent claim defining a nanoparticle with specific structural and functional features. The main inventive features focus on the nanoparticle core, its capability to absorb laser irradiation, and the specific streptavidin-biotin coating for targeting bacteria.
Nanoparticle core capable of absorbing laser irradiation
The nanoparticle comprises a core capable of absorbing laser irradiation, which can be a metal nanoparticle, a nanoparticle with a core-shell structure, or an electroceramic nanocomposite, enabling photothermal effects upon laser exposure.
Streptavidin-biotin coating for bacterial targeting
The nanoparticle core is coated with a streptavidin-biotin coating disposed on its surface, which is capable of binding specifically to target bacteria including methicillin resistant bacteria, Gram-positive and Gram-negative bacteria, or bacteria with surface peptidoglycan.
Metal nanoparticle or gold shell composition
The nanoparticle core may specifically be a gold nanoparticle or a silica nanoparticle coated with a gold shell, optimizing optical properties for laser absorption.
Pharmaceutical composition including nanoparticles
A pharmaceutical composition comprising the functional nanoparticle as defined, combined with a pharmaceutically acceptable carrier for treating microbial infections.
The inventive features define a nanoparticle designed for targeted photothermal treatment of bacterial infections, combining a laser-absorbing core with a streptavidin-biotin-based antibody coating for selective binding to bacteria, including drug-resistant strains, and a composition suitable for pharmaceutical applications.
Stated Advantages
Effectively inhibits growth of drug-resistant microbial strains and biofilms with laser irradiation.
Simplifies treatment by requiring attachment of only one antibody for targeting bacteria.
Offers a non-antibiotic treatment approach addressing growing bacterial resistance.
Can destroy or reduce bacterial biofilms and infections, including those involving biofilm formation.
Allows for selective targeting of bacteria through functional antibody coating enhancing specificity and minimizing nonspecific interactions.
Documented Applications
Treatment of microbial infections, including drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA).
Destruction or reduction of bacterial biofilms generated by microorganisms.
Topical treatment of wound surface bacterial infections with laser irradiation following application of antibody coated nanoparticles.
Potential treatment of internal infections, such as lung infection caused by tuberculosis, by adapting laser wavelength and delivery (e.g., using optic fibers).
Use in combination with antimicrobial agents including chitosan, lysostaphin, dispersin B, and antimicrobial peptides to enhance antibacterial effects.
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