Method of treating multi-drug resistance biofilm using targeted laser and antibiotics
Inventors
Assignees
Publication Number
US-11298561-B2
Publication Date
2022-04-12
Expiration Date
2033-05-23
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Abstract
This application describes a method of using gold nanoparticle (GNP)-targeted pulsed laser technology to enhance antibiotic efficacy against multidrug resistant biofilms. The application also teaches a method for treating topic wound infection using GNP-targeted laser therapy combined with antibiotics treatments.
Core Innovation
This invention relates to a method of treating wound infections and eradicating biofilms using gold nanoparticle (GNP)-targeted pulsed laser therapy in combination with administration of antimicrobial agents. The method involves introducing nanoparticles capable of binding to target microorganisms associated with wound infection into a wound or microbiological film, irradiating the area with pulsed electromagnetic radiation to generate photothermal and photoacoustic effects, and administering one or more antimicrobial agents to enhance treatment efficacy.
The problem being solved is the challenge of treating infections caused by multidrug resistant (MDR) pathogens, particularly those associated with biofilms. Biofilm-associated bacteria are significantly more tolerant to antibiotics due to factors such as decreased penetration of antimicrobial agents through the biofilm’s extracellular matrix and reduced metabolic activity of bacteria in nutrient-deprived regions. Existing treatments often rely on physical removal of biofilms, which leads to delayed wound healing, increased medical costs, and may contribute to treatment failure.
The invention addresses these challenges by exploiting the unique surface plasmon resonance properties of gold nanoparticles, which strongly absorb visible light and convert it to thermal energy rapidly upon pulsed laser irradiation. Antibody-coated GNPs specifically target biofilms, allowing localized photothermal and photoacoustic effects that disrupt the biofilm matrix and kill bacteria without significant bulk heating and damage to surrounding tissue. The combination with antimicrobial agents, such as antibiotics effective against the target microorganisms, synergistically enhances bacterial killing and biofilm disruption, offering a targeted, effective alternative to conventional therapies.
Claims Coverage
The patent contains two independent claims covering methods for treating wound infections and eradicating microbiological films, each incorporating the use of targeted nanoparticles, pulsed electromagnetic radiation, and administration of antimicrobial agents. Below are the main inventive features for these independent claims.
Method for treating wound infection using targeted nanoparticles and pulsed radiation with antimicrobial administration
The method involves introducing nanoparticles that have electron density capable of coupling with electromagnetic radiation and are capable of binding to one or more target microorganisms associated with wound infection. The wound is then irradiated by electromagnetic radiation, specifically by pulsed sources with pulse length in the range of 10-12 nanoseconds at a pulse rate of 1 pulse per second. One or more therapeutically effective doses of an antimicrobial agent, which may be antiseptics or antibiotics, are administered to the subject. The nanoparticles can be metal nanoparticles such as gold nanoparticles or silica nanoparticles coated with gold shells, and can be functionalized with antibodies or aptamers that bind to the target microorganisms.
Method for eradicating microbiological films using targeted nanoparticles, pulsed radiation and antimicrobial agents
The method comprises introducing a composition containing nanoparticles with electron density capable of coupling with electromagnetic radiation and capable of binding to microorganisms within the microbiological film. The film is irradiated with pulsed electromagnetic radiation (pulse length 10-12 nanoseconds, 1 pulse per second) to generate mechanical forces that locally disrupt the biofilm through expansion or collapse of vapor nanobubbles. Following irradiation, one or more antimicrobial agents are administered to the microbiological film. The microbiological film includes biofilms with microorganisms such as MRSA, Pseudomonas aeruginosa, and other bacteria. Nanoparticles used can be gold nanoparticles or silica coated with gold shells, functionalized with antibodies or aptamers.
The claims describe novel methods involving targeted nanoparticles capable of binding microorganisms within wounds or microbiological films, irradiation by pulsed electromagnetic radiation that induces localized photothermal and photoacoustic effects to disrupt biofilms, and co-administration of antimicrobial agents to synergistically treat infections or eradicate biofilms. The inventive features focus on the combination of targeted nanoparticles, pulsed laser irradiation parameters, and antibiotic or antiseptic administration for enhanced antimicrobial efficacy.
Stated Advantages
The method effectively eradicates multidrug resistant biofilms by dispersing extracellular matrix and killing resident bacteria with up to 96-99% biofilm removal and 90-98% bacterial killing.
The approach enhances antibiotic efficacy synergistically, achieving 4- to 5-log reductions in biofilm bacterial viability when combined with antibiotics like gentamicin or amikacin.
The use of nanosecond pulsed laser irradiation localizes thermal energy around nanoparticles and avoids bulk heating above the thermal injury threshold, minimizing collateral damage to healthy tissue.
The antibody-targeted gold nanoparticles enable site-specific binding and laser therapy, reducing nonspecific effects and improving treatment selectivity.
The method allows flexible antimicrobial regimens and timing, enabling tailored therapies based on patient culture results.
Documented Applications
Treatment of topical wound infections, including chronic wounds infected with multidrug resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and multidrug resistant Pseudomonas aeruginosa.
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