Nanoparticle conjugates of highly potent toxins and intraperitoneal administration of nanoparticles for treating or imaging cancer

A method of treating cancer in a human subject in need thereof comprising

• administering by intraperitoneal injection or infusion to the intraperitoneal cavity a composition comprising a plurality of particles in an aqueous pharmaceutically acceptable carrier,
• wherein
• the cancer is a cancer that forms a peritoneal implant on the serosal surface of an organ of the peritoneal cavity;
• each particle comprises a biodegradable core having an outer surface and a polymer non-covalently associated with the outer surface of the core;
• the biodegradable core comprises
• an agent, wherein the agent is (a) a nuclease selected from the group consisting of Cas9, TALEN, and zinc finger, or (b) a nucleic acid encoding a nuclease selected from the group consisting of Cas9, TALEN, and zinc finger;
• an optional DNA editing template;
• and
• a block copolymer comprising:
• (i) a first block comprising a plurality of first monomers, wherein each first monomer is selected from the group consisting of ethylene glycol, propylene glycol, vinyl alcohol, acrylic acid, methacrylic acid, methyl acrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, hydroxyethyl methacrylate, 2,3-dihydroxypropyl methacrylate, vinyl pyrrolidone, and dextrin;
• (ii) a second block comprising a plurality of second monomers, wherein each second monomer is hydrophobic;
• and
• (iii) a third block comprising a plurality of third monomers, wherein each third monomer is positively charged at a pH from about 6.8 to about 7.4,
• wherein
• the agent is non-covalently associated with the block copolymer;
• and
• the DNA editing template, when present, is non-covalently associated with the block copolymer;
• the polymer comprises a plurality of first monomers;
• and
• the characteristic size of the particles, as determined by dynamic light scattering (DLS), is about 20 nm to about 300 nm.

A particle comprising a biodegradable core having an outer surface and a polymer non-covalently associated with the outer surface of the core,

• wherein
• the biodegradable core comprises
• an anticancer agent;
• and
• a block copolymer comprising:
• (i) a first block comprising a plurality of first monomers, wherein each first monomer is selected from the group consisting of ethylene glycol, propylene glycol, vinyl alcohol, acrylic acid, methacrylic acid, methyl acrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, hydroxyethyl methacrylate, 2,3-dihydroxypropyl methacrylate, vinyl pyrrolidone, and dextrin;
• (ii) a second block comprising a plurality of second monomers, wherein each second monomer is selected from the group consisting of 6-hydroxycaproic acid, side-chain N-protected lysine, lactic acid, glycolic acid, hydroxybutyrate, valine, isoleucine, leucine, methionine, phenylalanine, tryptophan, cysteine, alanine, proline, glycine, tyrosine, side-chain carbonyl-protected aspartic acid, side-chain carbonyl-protected glutamic acid, propylene carbonate, butyl acrylate, butyl methacrylate, and benzyl methacrylate;
• and
• (iii) a third block comprising a plurality of third monomers, wherein each third monomer is selected from the group consisting of lysine, side-chain aminoalkyl-functionalized lysine, asparagine, side-chain aminoalkyl-functionalized asparagine, arginine, aspartamide, side-chain aminoalkyl-functionalized aspartamide, and ethyleneimine,
• wherein the anticancer agent is covalently bound to the block copolymer;
• the polymer comprises a plurality of first monomers, wherein each first monomer is selected from the group consisting of ethylene glycol, propylene glycol, vinyl alcohol, acrylic acid, methacrylic acid, methyl acrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, hydroxyethyl methacrylate, 2,3-dihydroxypropyl methacrylate, vinyl pyrrolidone, and dextrin;
• and
• the characteristic size of the particle, as determined by dynamic light scattering (DLS), is about 20 nm to about 300 nm.

A particle comprising a biodegradable core having an outer surface and a polymer non-covalently associated with the outer surface of the core,

• wherein
• the biodegradable core comprises
• an anticancer agent;
• and
• Pt(IV);
• the polymer comprises a plurality of first monomers, wherein each first monomer is selected from the group consisting of ethylene glycol, propylene glycol, vinyl alcohol, acrylic acid, methacrylic acid, methyl acrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, hydroxyethyl methacrylate, 2,3-dihydroxypropyl methacrylate, vinyl pyrrolidone, and dextrin;
• and
• the characteristic size of the particle, as determined by dynamic light scattering (DLS), is about 20 nm to about 300 nm

A particle comprising a core and a polymer non-covalently associated with the core, wherein

• the polymer comprises a plurality of first monomers, wherein each first monomer is selected from the group consisting of ethylene glycol, propylene glycol, vinyl alcohol, acrylic acid, methacrylic acid, methyl acrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, hydroxyethyl methacrylate, 2,3-dihydroxypropyl methacrylate, vinyl pyrrolidone, and dextrin;
• the core comprises an imaging agent;
• and
• the characteristic size of the particle, as determined by DLS, is about 20 nm to about 300 nm.