Near-infrared electromagnetic modification of cellular steady-state membrane potentials

Abstract

Systems and methods are disclosed herein for applying near-infrared optical energies and dosimetries to alter the bioenergetic steady-state trans-membrane and mitochondrial potentials (ΔΨ-steady) of all irradiated cells through an optical depolarization effect. This depolarization causes a concomitant decrease in the absolute value of the trans-membrane potentials ΔΨ of the irradiated mitochondrial and plasma membranes. Many cellular anabolic reactions and drug-resistance mechanisms can be rendered less functional and/or mitigated by a decrease in a membrane potential ΔΨ, the affiliated weakening of the proton motive force Δp, and the associated lowered phosphorylation potential ΔGp. Within the area of irradiation exposure, the decrease in membrane potentials ΔΨ will occur in bacterial, fungal and mammalian cells in unison. This membrane depolarization provides the ability to potentiate antimicrobial, antifungal and/or antineoplastic drugs against only targeted undesirable cells.

1 - 25 . (canceled) 
     
     
         26 . A method comprising:
 reducing the mammalian mitochondrian proton-motive force (Δp-mito-mam) and the mammalian plasma trans-membrane potential (ΔΨ-plas-mam) across a mammalian cell membrane in mammalian cancer cells of a target site in order to inhibit a cancer cellular anabolic pathways and weaken a resistance mechanism against antineoplastic molecules, the reducing step comprising:   combining An and Tn to irradiate a target site at a NIMELS dosimetry, concurrently reducing mammalian chemiosmotic electrochemical energy that is required for cellular anabolic reactions in mammalian cancer cells at said target site; and   simultaneously or sequentially administering an antineoplastic agent or agents to said target site, co-targeting a cellular anabolic reaction or reactions, wherein inhibition of one or more cellular anabolic pathways at said target site is effectuated;   wherein An corresponds to irradiation at wavelengths in at least one of the wavelength range of about 865 nm to about 875 nm and the wavelength range of about 925 nm to about 935 nm;   wherein Tn corresponds to a treatment time in the range of 50 seconds to about 1200 seconds; and   wherein the NIMELS dosimetry corresponds to irradiation of the target site at a power density of about 0.25 W/cm̂2 to about 40 W/cm̂2 and an energy density of about 50 J/cm̂2 to about 700 J/cm̂2.   
     
     
         27 . The method of  claim 26 , wherein An corresponds to irradiation at wavelengths in both the wavelength range of about 865 nm to about 875 nm and the wavelength range of about 925 nm to about 935 nm. 
     
     
         28 . The method of  claim 26 , wherein An corresponds to irradiation at wavelengths in the wavelength range of about 865 nm to about 875 nm. 
     
     
         29 . The method of  claim 26 , wherein An corresponds to irradiation at wavelengths in the wavelength range of about 925 nm to about 935 nm. 
     
     
         30 . The method of  claim 26 , wherein the target site is an in vivo target site in a human or animal subject, the target cells comprises a cancer cells in the site, and wherein combining An and Tn to irradiate a target site at a NIMELS dosimetry comprises irradiating the target site without causing substantial thermal damage to the subject at target site. 
     
     
         31 . The method of  claim 26 , comprising combining An and Tn to irradiate a target site, where inhibition of cancer cellular anabolic pathways is further enhanced with the simultaneous or sequential administration of a pharmacological agent or agents that also inhibit cancer anabolic pathways. 
     
     
         32 . The method of  claim 26 , comprising potentiating the antineoplastic agent with a Nimels effect number Ne of at least 1. 
     
     
         33 . The method of  claim 26 , wherein the antineoplastic agent comprises at least one from the list consisting of: actinomycin, anthracyclines, bleomycin, plicamycin, mitomycin, taxanes, etoposide, teniposide, combinations thereof, and salts thereof. 
     
     
         34 . The method of  claim 26 , wherein the reducing step comprises mechano-optically modifying a thermodynamic interaction of a cell membrane of the mammalian cancer cells. 
     
     
         35 . A method comprising:
 reducing the mammalian mitochondrian proton-motive force (Δp-mito-mam) and the mammalian plasma trans-membrane potential (ΔΨ-plas-mam) across a mammalian cell membrane in mammalian cancer cells of a target site in order to potentiate one or more antineoplastic agent to counteract resistance mechanisms in the cancer cells, so that the antineoplastic agent can inhibit the growth or proliferation of the cancer at a lower concentration than would be necessary in the absence of the reducing step, the reducing step comprising:
 combining An and Tn to irradiate a target site at a NIMELS dosimetry, concurrently reducing mammalian chemiosmotic electrochemical energy that is required for cellular anabolic reactions in can cells at said target site; and 
 simultaneously or sequentially administering an antineoplastic agent to said target site, co-targeting cellular anabolic reactions wherein inhibition of one or more cellular anabolic pathways at said target site is effectuated; 
   wherein An corresponds to irradiation at wavelengths in at least one of the wavelength range of about 865 nm to about 875 nm and the wavelength range of about 925 nm to about 935 nm;   wherein Tn corresponds to a treatment time in the range of 50 seconds to about 1200 seconds; and   wherein the NIMELS dosimetry corresponds to irradiation of the target site at a power density of about 0.25 W/cm′̂2 to about 40 W/cm̂2 and an energy density of about 50 J/cm̂2 to about 700 J/cm̂2.   
     
     
         36 . The method of  claim 35 , comprising potentiating the antineoplastic agent with a Nimels effect number Ne of at least 1. 
     
     
         37 . The method of  claim 35 , wherein the antineoplastic agent comprises at least one from the list consisting of: actinomycin, anthracyclines, bleomycin, plicamycin, mitomycin, taxanes, etoposide, teniposide, combinations thereof, and salts thereof.