PEG AND TARGETING LIGANDS ON NANOPARTICLE SURFACE
Provided are compositions of nanoparticles, PEG and targeting moieties. The compositions are useful in treating tumors, imaging the particles in tissues, and in targeting therapeutic agents to specific tissues and locations in a patient. Also provided are methods of preparing and methods of using the compositions.
1 . A method of treating a tumor in a subject, the method comprising contacting a subject in need thereof with a nanoparticle comprising at least one polymer and at least one therapeutic agent joined thereto, under suitable conditions such that at least one tumor-related effect occurs.
2 . The method of claim 1 wherein the suitable conditions comprise a sustained time period of at least 1 day, at least 2 days, at least 5 days, at least 10 days, at least 20 days, at least 30 days, at least 45 days, and at least 60 days.
3 . The method of claim 1 wherein the polymer is selected from the group consisting of: aliphatic polyesters; poly(glycolic acid); poly(lactic-co-glycolic acid); poly(caprolactone glycolide)); poly(lactic acid); polylactide (PLA); poly-L(lactic acid); poly-D Lactic acid; poly(caprolactone lactide); poly(lactide glycolide), poly(lactic acid ethylene glycol)); poly(ethylene glycol); poly(lactide); polyalkylene succinate; polybutylene diglycolate; polyhydroxybutyrate (PHB); polyhydroxyvalerate (PHV); polyhydroxybutyrate/polyhydroxyvalerate copolymer (PHB/PHV); poly(hydroxybutyrate-co-valerate); polyhydroxyalkaoates (PHA); polycaprolactone; polydioxanone; polyanhydrides; polyanhydride esters; polycyanoacrylates; poly(alkyl 2-cyanoacrylates); poly(amino acids); poly(phosphazenes); poly(propylene fumarate); poly(propylene fumarate-co-ethylene glycol); poly(fumarate anhydrides; poly(iminocarbonate); poly(BPA-iminocarbonate); poly(trimethylene carbonate); poly(iminocarbonate-amide) copolymers and/or other pseudo-poly(amino acids); poly(ethylene glycol); poly(ethylene oxide); poly(ethylene oxide)/poly(butylene terephthalate) copolymer; poly(epsilon-caprolactone-dimethyltrimethylene carbonate); poly(ester amide); poly(amino acids) and conventional synthetic polymers thereof; poly(alkylene oxalates); poly(alkylcarbonate); poly(adipic anhydride); nylon copolyamides; NO-carboxymethyl chitosan NOCC); carboxymethyl cellulose; copoly(ether-esters) (e.g., PEO/PLA dextrans); polyketals; biodegradable polyethers; and biodegradable polyesters.
4 . The method of claim 3 wherein the polymer comprises polylactide or poly(lactic-co-glycolic acid).
5 . The method of claim 1 wherein the therapeutic agent is selected from the group consisting of: a polysaccharide, a peptide, a polypeptide, a nucleic acid, a vitamin, a mineral, a vaccine, a cytokine, an apoptotic agent, a cytotoxic agent, and a pharmaceutical drug.
6 . The method of claim 5 wherein the therapeutic agent comprises paclitaxel, dexamethasone, a heat-shock protein, Bcl-2, Bcl-xl, or folic acid.
7 . The method of claim 1 wherein the nanoparticle further comprises a detection agent joined thereto, wherein the detection agent is selected from the group consisting of: a magnetic compound, a paramagnetic compound, a fluorophore, a radioisotope, and an enzyme.
8 . The method of claim 1 or claim 7 wherein the nanoparticle further comprises a functional group joined thereto, wherein the functional group is selected from the group consisting of: alkane, alkene, alkyne, amide, amine, imide, phosphine, phosphodiester, phosphonic acid, phosphate, sulfide, imidazole and oxazole.
9 . The method of claim 1 wherein the tumor-related effect is selected from the group consisting of: decrease in tumor size, decrease in tumor cell proliferation, decrease in tumor cell metastasis, decrease in tumor vasculature, decrease in tumor angiogenesis, decrease in tumor blood flow, increase in cell differentiation, increase in tumor cell apoptosis, and increase in tumor cell necrosis.
10 . A therapeutic composition comprising a nanoparticle, and at least one therapeutic agent joined thereto wherein the therapeutic agent confers a sustained biological or chemical effect over a time period.
11 . The composition of claim 10 , wherein the time period is selected from the group consisting of: at least 1 day, at least 2 days, at least 5 days, at least 10 days, at least 20 days, at least 30 days, at least 40 days, and at least 60 days.
12 . The composition of claim 10 wherein the therapeutic agent is selected from the group consisting of: a polysaccharide, a peptide, a polypeptide, a nucleic acid, a vaccine, a cytokine, an apoptotic agent, a cytotoxic agent, a vitamin, a mineral, and a pharmaceutical drug.
13 . The composition of claim 12 wherein the therapeutic agent comprises paclitaxel, dexamethasone, a heat-shock protein, Bcl-2, Bcl-xl, or folic acid.
14 . The composition of claim 10 wherein the biological or chemical effect is selected from the group consisting of: decrease in tumor size, decrease in tumor cell proliferation, decrease in tumor cell metastasis, decrease in tumor vasculature, decrease in tumor angiogenesis, decrease in tumor blood flow, increase in cell differentiation, increase in tumor cell apoptosis, and increase in tumor cell necrosis.
15 . The composition of claim 10 wherein the nanoparticle further comprises a detection agent joined thereto.
16 . The composition of claim 15 wherein the detection agent is selected from the group consisting of: a magnetic compound, a paramagnetic compound, a fluorophore, a radio-isotope, and an enzyme.
17 . The composition of claim 10 wherein the nanoparticle further comprises a functional group joined thereto.
18 . The composition of claim 17 wherein the functional group is selected from the group consisting of: alkane, alkene, alkyne, amide, amine, imide, phosphine, phosphodiester, phosphonic acid, phosphate, sulfide, imidazole and oxazole.
19 . A process of making a nanoparticle composition comprising a first step of emulsifying at least one first agent in the presence of at least one first polymer and at least one first solvent, thereby forming a water-in-oil emulsion; and a second step of emulsifying the water-in-oil emulsion with at least one second polymer, at least one second solvent, and at least one second agent wherein the first and second agents are the same or different and are selected from the group consisting of a therapeutic agent, a diagnostic agent, and a detection agent; thereby making a nanoparticle composition.
20 . The process of claim 19 , wherein the first polymer comprises poly(lactic co-glycolic acid) (PLGA), the first solvent comprises polyvinyl alcohol, the first agent comprises paclitaxel, dexamethasone, a heat-shock protein, Bcl-2, Bcl-xl, or folic acid, the second polymer comprises polylactide (PLA) or polyethylene glycol (PEG), the second solvent comprises methanol, and the second agent comprises folic acid.
21 . A therapeutic composition comprising a nanoparticle, and at least one detection agent joined thereto wherein the detection agent confers a sustained biological or chemical effect over a time period.
22 . The composition of claim 21 wherein the detection agent is selected from the group consisting of: a magnetic compound, a paramagnetic compound, a fluorophore, a radio-isotope, and an enzyme.