Method of using laser-induced optoacoustics for the treatment of drug-resistant microbial infections
Inventors
Millenbaugh, Nancy J. • DeSilva, Mauris • Baskin, Jonathan • Elliot, William R
Assignees
Publication Number
US-10835755-B2
Publication Date
2020-11-17
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 biolfilm with laser irradiation.
Core Innovation
The invention relates to functional antibody coated nanoparticles that can be used as photothermal agents to inhibit the growth of microbes, including drug-resistant strains and biofilms, by laser irradiation. These nanoparticles comprise a core capable of absorbing laser irradiation, such as metal nanoparticles or core-shell nanostructures, and an antibody coating capable of recognizing target microorganisms like Gram-positive or Gram-negative bacteria. The nanoparticles can be prepared through binding antibodies to nanoparticle surfaces using methods such as covalent bonds, electrostatic interaction, or streptavidin-biotin bonds.
The problem addressed is the increasing difficulty in treating microbial infections due to the emergence of multidrug-resistant bacteria like methicillin resistant Staphylococcus aureus (MRSA). Traditional antibiotic therapies are losing effectiveness because bacterial resistance develops faster than new antibiotics. Existing photodynamic therapies have limitations in hypoxic environments and prior methods for nanoparticle targeting have been complex or ineffective against MRSA strains with variable surface protein expression. Thus, there is an urgent need for novel antimicrobial therapies that do not rely solely on antibiotics and that use nanoparticles with specific biological targeting to overcome limitations of prior methods.
This invention solves the problem by providing a simpler and effective method to selectively kill drug resistant bacteria using antibody functionalized nanoparticles combined with pulsed laser irradiation. The invention requires only a single type of antibody coating which targets bacterial surface components such as peptidoglycan. Additionally, the nanoparticles can be used to treat infections including biofilms and may be combined with antimicrobial adjuvants prior to laser treatment to enhance effectiveness. The approach also explores treatment of internal infections using appropriate laser wavelengths and delivery.
Claims Coverage
The patent includes multiple independent claims covering methods of treating microbial infections and preventing biofilm formation using antibody coated nanoparticles combined with laser irradiation.
Method of treating microbial infection using antibody coated nanoparticles and pulsed laser irradiation
Administrating a therapeutically effective dose of antibody coated nanoparticles to a subject suspected of microbial infection, followed by exposing the subject to pulsed laser irradiation where the antibody specifically binds to the microbe causing the infection.
Method including coadministration of antimicrobial agents with antibody coated nanoparticles and laser irradiation
Administrating antibody coated nanoparticles and coadministering antimicrobial agents such as endopeptidase lysostaphin, Chitosan, dispersin B, ranalexin, or LL-37 before exposing the subject to pulsed laser irradiation for treating microbial infection.
Method of using a pharmaceutical composition comprising antimicrobial antibody bonded nanoparticles and a pharmaceutically acceptable carrier for microbial infection treatment
Administering an effective dose of the pharmaceutical composition containing antimicrobial antibody bonded nanoparticles with a pharmaceutically acceptable carrier, and exposing the subject to laser irradiation of wavelength from 300 nm to 1500 nm, optionally with additional antimicrobial agents.
Method for preventing or reducing biofilm formation by microorganisms using antibody coated nanoparticles and laser irradiation
Administrating therapeutically effective doses of antibody coated nanoparticles to a subject suspected of infection, exposing the subject to laser irradiation generated by a high peak power pulsed laser with pulse widths less than 100 microseconds, optionally including coadministration of antimicrobial agents such as endopeptidase lysostaphin, Chitosan, dispersin B, ranalexin, or LL-37.
The independent claims collectively cover methods using antibody coated nanoparticles combined with pulsed laser irradiation to treat microbial infections and biofilms, optionally with coadministration of specified antimicrobial agents, specifying characteristics of the laser irradiation and the pharmaceutical compositions used to carry the nanoparticles.
Stated Advantages
The functional antibody coated nanoparticles enable selective killing of drug resistant bacteria through a non-antibiotic mechanism.
The method simplifies prior art by requiring attachment of only one antibody, improving effectiveness against both methicillin sensitive and resistant bacteria.
The photothermal killing mechanism avoids issues of bacterial resistance that challenge antibiotic and photodynamic therapies.
The treatment can be applied to both microbial biofilms and planktonic bacteria, including infections within the body using appropriate laser delivery techniques.
Documented Applications
Treatment of bacterial infections including drug resistant strains such as methicillin resistant Staphylococcus aureus (MRSA) using antibody coated nanoparticles and pulsed laser irradiation.
Reduction or prevention of microbial biofilm formation on infected tissues via administration of antibody coated nanoparticles combined with laser irradiation.
Topical treatment of wounds infected by bacteria using antibody coated nanoparticles with laser irradiation and optionally antimicrobial agents.
Treatment of internal infections like lung infections (e.g., tuberculosis) by delivering laser irradiation via optical fibers at near-infrared wavelengths targeting sites where antibody coated nanoparticles have been administered.
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