Method to change the polarization of tumor associated macrophages by exposing them to a source of radiation in the presence of magnetosomes

A method to control or change the polarization of at least one macrophage associated with a tumor or pathological site (TAM), from being predominantly a TAM with either no polarization (M0) or a polarization i (Mi) before at least one step of the method, to a predominant polarization j (Mj) after at least one step of the method, wherein the method comprises the following steps:

• step 1 providing i) and ii):
• i) at least one nanoparticle which is:
• a magnetosome synthesized by a magnetotactic bacterium or by at least one of its components, preferentially not comprising at least one non-denatured protein and/or lipid and/or LPS and/or DNA and/or RNA originating from or produced by or comprised in a magnetotactic bacterium or at least one of its components,
• a chemically synthesized nanoparticle, having at least one property in common with a magnetosome, preferentially selected in the group consisting of:
• i) a ferrimagnetic or ferromagnetic behavior or property, ii) an arrangement in chain or in a geometric figure, iii) a percentage in iron larger than 50, 75, 90, 95 or 99%, iv) the presence of a core, preferentially ferrimagnetic and/or metallic, and v) the presence of a coating surrounding partly or fully the core,
• and/or
• a nanoparticle that has at least one property selected in the group consisting of:
• 1) the nanoparticle is composed of or comprises at least 2 metals or metal atoms, which are surrounded by or mixed with or bound through or interacting through or assembled by part of or the entire of an organelle or cellular vesicle or endosome or exosome or lysosome or cellular compartment, preferentially intracellular, most preferentially inside an eukaryotic cell, preferentially belonging to or originating from a pathological cell,
• and
• 2) the nanoparticle forms a nanoparticle or a particle with a size smaller than 1000, 100, 50, 20, 10, 5, 2 or 1 nm, preferentially in at least one dimension or cross section of the nanoparticle or particle, through the composition of at least 1 or 2 metals or metal atoms, which is/are surrounded by or mixed with or bound through or interacting through or assembled by or transformed into a nanoparticle or particle that has at least one property that differs from that of a single atom, or made crystallized or magnetic, preferentially diamagnetic, paramagnetic, superparamagnetic, ferromagnetic or ferrimagnetic, by part of or the entire of an organelle or cellular vesicle or endosome or exosome or lysosome or cellular compartment, preferentially intracellular, most preferentially inside an eukaryotic cell, preferentially belonging to or originating from a pathological cell,
• and
• ii) at least one TAM, having at least one property selected in the group consisting of:
• i) it is a TAM with either no polarization (M0) or with polarization i (Mi), ii) at least two TAM forming an assembly of TAM with predominantly polarization(s) (M0) and/or (Mi) and/or with a minority of or no polarization (Mj), ii) it is comprised in or is extracted from or originates from or is produced by or is differentiated in or by a pathological site or tumor or body part to be treated or its/their environment or microenvironment, partly or fully, iii) it is differentiated from a mast or stem or un-differentiated cell, iv) it is moving or in movement or is migrating, and v) it is provided, collected, harvested, detected, differentiated, isolated, activated, polarized;
• step 2 comprising assembling and/or mixing, and/or conjugating, and/or complexing at least one nanoparticle of step 1 with at least one TAM of step 1 by:
• i) administering and/or assembling and/or mixing and/or conjugating and/or complexing the at least one nanoparticle of step 1 to or with a body part comprising at least one TAM of step 1;
• ii) bringing together the at least one TAM of step 1 and at least of nanoparticle of step 1;
• iii) internalizing at least one nanoparticle of step 1 in at least one TAM of step 1;
• iv) externalizing or expelling at least one nanoparticle of step 1 from at least one TAM of step 1;
• and/or
• associating and/or assembling and/or mixing and/or conjugating and/or complexing at least one nanoparticle of step 1 and at least of TAM of step 1;
• step 3 comprising exposing or having exposed or letting exposed, preferentially by the body part, or at least one compound or radiation in or outside the body part, the nanoparticle(s) and/or TAM(s) of step 1 and/or assembly, and/or mixture, and/or conjugate, and/or complex and/or composite and/or compound and/or blend of nanoparticle(s) and/or TAM(s) of step 2 and/or its/their environment to at least one of:
• a) a variation of at least one radiation parameter;
• b) a movement and/or displacement;
• c) a temperature gradient;
• d) a pH gradient;
• and
• e) a composition gradient;
• wherein the environment of the nanoparticle(s) and/or TAM(s) is at least one region or volume comprising the nanoparticle(s) and/or TAM,
• optionally step 4 of:
• i) stopping the application of radiation after step 3;
• or
• ii) exposing the assembly or mixture or conjugate or complex, or compound, or composite, or blend, resulting from step 3 of the method to a different source of radiation than that applied in step 3 or to the same source of radiation as that applied in step 3, but with at least one of its parameter with a different value than in step 3.
• optionally step 5 of detecting or measuring or differentiating at least one cell, being a monocyte or TAM (M0, M1, or M2), or property associated with the at least one state of the cell, such as the morphology, size, directional movement, production of type, size, number of immune entities or the cell,
• optionally step 6 of differentiating at least one monocyte into an unpolarized TAM by:
• i) associating at least one monocyte with at least one entity that differentiates the monocyte into a TAM, and/or
• ii) associating at least one nanoparticle of step 1 with at least one monocyte, and of exposing the assembly of at least one nanoparticle and monocyte to at least one radiation, wherein Mi=M1 and Mj=M2 or Mi=M2 and Mj=M1.