Magnetically responsive nanoparticle therapeutic constructs and methods of making and using
First Claim
1. A method for delivering a therapeutic to target cells within a body, the method comprising the following steps:
- preparing magnetically responsive therapeutic constructs comprising;
magnetically responsive carrier nanoparticles selected from the group consisting of;
(a) single-domain nanoparticles comprising magnetite and having an average particle size ranging between 1 and 50 nanometers, (b) clusters of single-domain nanoparticles comprising magnetite, the particles having an average particle size ranging between 1 and 50 nanometers, the clusters having an average cluster ranging between 5 and 1000 nanometers, and mixtures of (a) and (b);
a silica coating encapsulating the single-domain nanoparticles;
a silane coupling agent bonded to the silica coating and having a specific pendant functional group comprises a carboxyl group capable of selectively binding with the therapeutic; and
the therapeutic chemically bonded to the silane coupling agent;
wherein the silane coupling agent comprises an alkoxysilylpropyl-O-polyethylene oxide urethane containing monomer units of polyethylene glycol (PEG) terminating in an alcohol function which has been oxidized to a carboxyl group;
introducing the magnetically responsive therapeutic constructs into the body; and
moving the therapeutic constructs to the target cell using a controllable magnetic field generator adapted to move the carrier nanoparticles in three dimensions.
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Abstract
Magnetically responsive therapeutic carriers comprise nanoparticles including single-domain nanoparticles comprising magnetite and having an average particle size ranging between 1 and 50 nanometers, clusters of the single-domain nanoparticles, the clusters having an average cluster size ranging between 5 and 1000 nanometers, and mixtures of the two. The single-domain nanoparticles are encapsulated with a silica coating. A silane coupling agent is bonded to the silica coating and has a specific pendant functional group capable of selectively binding with the therapeutic. Preferably, the bond between the specific pendant functional group and the therapeutic is a covalent bond. The movement of magnetically responsive nanoparticle therapeutic constructs, with concentration and extravasation/endocytosis at a target site, such as cancerous tumors, uses a controllable magnetic field generator adapted to move the therapeutic constructs in three dimensions, and is enhanced using a repetitively-varying magnetic field. A method for treating cancer comprises administering and magnetically guiding a therapeutic construct comprising paclitaxel.
96 Citations
23 Claims
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1. A method for delivering a therapeutic to target cells within a body, the method comprising the following steps:
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preparing magnetically responsive therapeutic constructs comprising; magnetically responsive carrier nanoparticles selected from the group consisting of;
(a) single-domain nanoparticles comprising magnetite and having an average particle size ranging between 1 and 50 nanometers, (b) clusters of single-domain nanoparticles comprising magnetite, the particles having an average particle size ranging between 1 and 50 nanometers, the clusters having an average cluster ranging between 5 and 1000 nanometers, and mixtures of (a) and (b);a silica coating encapsulating the single-domain nanoparticles; a silane coupling agent bonded to the silica coating and having a specific pendant functional group comprises a carboxyl group capable of selectively binding with the therapeutic; and the therapeutic chemically bonded to the silane coupling agent; wherein the silane coupling agent comprises an alkoxysilylpropyl-O-polyethylene oxide urethane containing monomer units of polyethylene glycol (PEG) terminating in an alcohol function which has been oxidized to a carboxyl group; introducing the magnetically responsive therapeutic constructs into the body; and moving the therapeutic constructs to the target cell using a controllable magnetic field generator adapted to move the carrier nanoparticles in three dimensions. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21)
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22. A method for treating cancer in a subject, comprising administering to a subject having cancer a therapeutic construct comprising:
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magnetically responsive nanoparticles selected from the group consisting of; (a) single-domain nanoparticles comprising magnetite and having an average particle size ranging between 1 and 50 nanometers, (b) clusters of single-domain nanoparticles comprising magnetite, the particles having an average particle size ranging between 1 and 50 nanometers, the clusters having an average cluster size ranging between 5 and 1000 nanometers, and mixtures of (a) and (b); a silica coating encapsulating the single-domain nanoparticles; a first silane coupling agent bonded to the silica coating and having a pendant carboxyl groups capable of selectively binding with a therapeutic; wherein the first silane coupling agent comprises an alkoxysilylpropyl-O-polyethylene oxide urethane containing monomer units of polyethylene glycol (PEG) terminating in an alcohol function which has been oxidized to a carbox group; and the therapeutic comprising a taxane selected from the group consisting of paclitaxel, docetaxel and mixtures of the same. - View Dependent Claims (23)
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Specification