Screening of a library of particles in vivo and/or in vitro using Polyplex Iterative Combinatorial Optimization (PICO) allows for the design of particles for targeting a specific organ, tissue (e.g., cancer), or cell. Particles may, for example, include different targeting agents (e.g., aptamers or
Screening of a library of particles in vivo and/or in vitro using Polyplex Iterative Combinatorial Optimization (PICO) allows for the design of particles for targeting a specific organ, tissue (e.g., cancer), or cell. Particles may, for example, include different targeting agents (e.g., aptamers or plurality of aptamers) on their surfaces, and the aptamer or aptamers may be evolved to provide better targeting of the particles. Libraries of particles are enriched in characteristics of particles that have been found to migrate to a tissue of interest, be taken up by cells, etc. The process may be repeated to engineer particles of a desired specificity or biological function.
대표청구항▼
1. A high throughput, iterative, combinatorial screening method of identifying targeting agents or particle properties providing enhanced uptake of particles into targeted cells in tissue, the method comprising the steps of providing a plurality of synthetic polymeric particle populations,wherein th
1. A high throughput, iterative, combinatorial screening method of identifying targeting agents or particle properties providing enhanced uptake of particles into targeted cells in tissue, the method comprising the steps of providing a plurality of synthetic polymeric particle populations,wherein the particles of each population have substantially the same composition, size, density, surface chemistry, targeting agent or density of targeting agent bound thereto, wherein the particles of a given particle population differ from the particles of another given particle population by at least one particle characteristic, andwherein each particle of a given population has at least one detectable label which is different from the detectable label of the particles of another given particle population and is different from the targeting agent;administering the plurality of particle populations to an animal under conditions in which the particles are taken up by cells of a targeted tissue; andenriching the uptaken particles by repeating the process with different populations of particles,each population having at least one different particle characteristic, thereby determining the particle characteristics which enhance uptake of the particles by the cells of the targeted tissue. 2. The method of claim 1, wherein the particles have on the surface thereof a targeting agent selected from the group consisting of an oligonucleotide, a polysaccharide, an antibody, an antibody fragment, a nucleic acid ligand, a lipoprotein, folate, transferrin, an asialycoprotein, an enzymatic receptor ligand, sialic acid, a glycoprotein, a lipid, a small molecule, metal, metal complex, a bioactive agent, and an immunoreactive fragment. 3. The method of claim 1, wherein the detectable label is selected from the group consisting of a luminescent agent, a chemiluminescent agent, a phosphorescent agent, a fluorescent agent, a radionuclide, a small molecule, a mass spectroscopy tag, a polynucleotide, a polypeptide, a semiconductor particle, a magnetic material, an ultrasound contrast agent, an MRI contrast agent, and an x-ray contrast agent. 4. The method of claim 3, wherein the label is disposed on the surface of the particle, in the interior of the particle, or both. 5. The method of claim 1 further comprising the step of recovering particles that have migrated to cells of a non-targeted tissue. 6. The method of claim 1, wherein the particles are selected from the group consisting of microparticles, nanoparticles, and picoparticles. 7. The method of claim 1, wherein the polymer is selected from the group consisting of polyesters, polyamides, polycarbonates, polycarbamates, polyacrylates, polystyrene, polyureas, polyethers, polyamines, polyanhydrides, poly(hydroxyacids), poly(lactic acid), poly(glycolic acid), poly(orthoesters), polyphosphazene, ethylene-vinyl acetate copolymer, polyurethanes, polyacrylates, polymethacrylates, polyacrylonitriles, poly(amidoamine) dendrimers, poly(L-lactide-co-L-lysine), poly(serine ester), poly(4-hydroxy-L-proline ester), maleimide-poly(ethyleneglycol)-block-poly(D,L-lactic acid); COOH-poly(ethyleneglycol)-block-poly(D,L-lactic acid); methoxypoly(ethyleneglycol)-block-poly(D,L-lactic acid); proteins; polysaccharides, PEGylated poly(hydroxy acids), PEGylated poly(orthoesters), poly(caprolactone), PEGylated poly(caprolactone), polylysine, PEGylated polylysine, poly(ethylene imine), PEGylated poly(ethylene imine), and combinations thereof. 8. The method of claim 7, wherein the particles are poly(lactic-co-glycolic acid) (PLGA) particles. 9. The method of claim 1, wherein the particles comprise at least one targeting agent. 10. The method of claim 1, wherein the particles comprise a plurality of targeting agents. 11. The method of claim 1 wherein the particles of each of the given particle populations have a different collection of aptamers conjugated to their surface. 12. The method of claim 1, wherein the particles comprise a poly(hydroxy acid) polymer or copolymer or pegylated poly(hydroxy acid) polymer or copolymer.
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Gerster John F. (Woodbury MN) Crooks Stephen L. (Mahtomedi MN) Lindstrom Kyle J. (Houlton WI), 1-substituted, 2-substituted 1H-imidazo[4,5-c]quinolin-4-amines.
Schmitz,Juergen; Dzionek,Andrzej; Buck,David William, Antigen-binding fragments specific for dendritic cells, compositions and methods of use thereof antigens recognized thereby and cells obtained thereby.
Arimilli Murty N. ; Cundy Kenneth C. ; Dougherty Joseph P. ; Kim Choung U. ; Oliyai Reza ; Stella Valentino J., Antiviral phosphonomethoxy nucleotide analogs having increased oral bioavailability.
Hubbard Vance M. (Bedford) Brunson Welton K. (Bedford) Saied V. C. (Wichita Falls TX), Apparatus and method for raising a skin wheal and anesthetizing skin.
Flatt James H. ; Applegate Mark A. ; Peterson Alvin, Apparatus and method for sterilizing, seeding, culturing, storing, shipping and testing replacement cartilage tissue constructs.
Mikos Antonios G. (Houston TX) Sarakinos Georgios (Boston MA) Vacanti Joseph P. (Winchester MA) Langer Robert S. (Newton MA) Cima Linda G. (Lexington MA), Biocompatible polymer membranes and methods of preparation of three dimensional membrane structures.
Barrera Denise (Oakdale MN) Langer Robert S. (Newton MA) Lansbury ; Jr. Peter T. (Brookline MA) Vacanti Joseph P. (Winchester MA), Biodegradable polymers for cell transplantation.
Vacanti Joseph P. ; Vacanti Charles A. ; Langer Robert S., Biodegradable synthetic polymeric fibrous matrix containing chondrocyte for in vivo production of a cartilaginous struct.
D\Amore Patricia (Brookline MA) Leong Kam W. (Cambridge MA) Langer Robert S. (Somerville MA), Bioerodible articles useful as implants and prostheses having predictable degradation rates.
Skwierczynski Raymond D. ; Phares Kenneth R. ; Miller Richard L. ; Li Zheng Jane ; Jozwiakowski Michael J. ; Busch Terri F., Formulations and methods for treatment of mucosal associated conditions with an immune response modifier.
Dalton,James T.; Miller,Duane D.; Steiner,Mitchell S.; Veverka,Karen A., Halogenated selective androgen receptor modulators and methods of use thereof.
Swain Philip A. ; Schad Victoria C. ; Greenstein Julia L. ; Exley Mark A. ; Fox Barbara S. ; Powers Stephen P. ; Gefter Malcolm L., Hapten-carrier conjugates for use in drug-abuse therapy and methods for preparation of same.
Kedl,Ross M.; Griesgraber,George W.; Zarraga,Isidro Angelo E.; Wightman,Paul D., Immunostimulatory compositions and methods of stimulating an immune response.
Lilley Stephen J. (Sawston GBX) Taylor Hugh F. (Sawston GBX) Theobald David R. (Huntingdon GBX) Carlson Craig J. (Andover MA) Rosen David I. (Arlington MA) Johnson Thomas R. (Milford NH), Medical injection system and method, gas spring thereof and launching device using gas spring.
Tice Thomas R. ; Gilley Richard M. ; Eldridge John H. ; Staas Jay K., Method for delivering bioactive agents into and through the mucosally-associated lymphoid tissues and controlling their.
Bengs, Holger; Grande, Jürgen; Schuth, Silke; Böhm, Gitte; Schneller, Arnold; Brunner, Anette, Method for preparing smooth-surface spherical microparticles completely or partially made of at least one water-insoluble linear polysaccharide and microparticles produced according to this method.
Bomberger David C. ; Catz Paul G. ; Smedley Mark I. ; Stearns Paul C., Method for producing drug-loaded microparticles and an ICAM-1 dosage form so produced.
Deming, Timothy J.; Yu, Miaoer; Curtin, Scott A.; Hwang, Jungyeon; Wyrsta, Michael D.; Nowak, Andrew; Seidel, Scott W., Methods and compositions for controlled polypeptide synthesis.
Speaker Tully J. (Philadelphia PA) Sultzbaugh Kenneth J. (Philadelphia PA), Microcapsules of predetermined peptide(s) specificity (ies), their preparation and uses.
Jacobson Stephen C. ; Ramsey J. Michael, Microfabricated device and method for multiplexed electrokinetic focusing of fluid streams and a transport cytometry method using same.
Horoszewicz Julius S. (Williamsville NY), Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients.
Domb Abraham J. (Efrat ILX) Gref Ruxandra (Nancy FRX) Minamitake Yoshiharu (Ota JPX) Peracchia Maria T. (Parma ITX) Langer Robert S. (Newton MA), Nanoparticles and microparticles of non-linear hydrophilic-hydrophobic multiblock copolymers.
Domb Abraham J.,ILX ; Gref Ruxandra,FRX ; Minamitake Yoshiharu,JPX ; Peracchia Maria Teresa,ITX ; Langer Robert S., Nanoparticles and microparticles of non-linear hydrophilic-hydrophobic multiblock copolymers.
Mirkin, Chad A.; Letsinger, Robert L.; Mucic, Robert C.; Storhoff, James J.; Elghanian, Robert; Taton, Thomas A.; Garimella, Viswanadham; Li, Zhi, Nanoparticles having oligonucleotides attached thereto and uses therefor.
McKinnon ; Jr. Charles N. (Laguna Niguel CA) Peterson Steven F. (West Linn OR) Smith Paul E. (Tualatin OR) Nakagawa Takaaki (Tigard OR) Bartholomew Victor L. (Tigard OR), Needleless hypodermic injection device.
Peterson Steven F. (West Linn OR) McKinnon ; Jr. Charles N. (Laguna Niguel CA) Smith Paul E. (Tualatin OR) Nakagawa Takaaki (Tigard OR) Bartholomew Victor L. (Tigard OR), Needleless hypodermic injection methods and device.
Bischofberger Norbert W. ; Jones Robert J. ; Arimilli Murty N. ; Lin Kuei-Ying ; Louie Michael S. ; McGee Lawrence R. ; Prisbe Ernest J. ; Lee William A. ; Cundy Kenneth C., Nucleotide analogs.
Santus Giancarlo (Milan ITX) Bottoni Giuseppe (Bergamo ITX) Sala Giovanni (Verona ITX), Pharmaceutical controlled-release composition with bioadhesive properties.
DeLuca Patrick P. (Lexington KY) Kanke Motoko (Fukuyama JPX) Sato Toyomi (Tokyo CA JPX) Schroeder Hans G. (Encinitas CA), Porous microspheres for drug delivery and methods for making same.
Fessi Curt (Paris FRX) Devissaguet Jean-Philippe (Neuilly S/Seine FRX) Puisieux Francis (Maisons Alfort MO FRX) Thies Curt (St. Louis MO), Process for the preparation of dispersible colloidal systems of a substance in the form of nanoparticles.
Stainmesse Serge (Choisy le Roi FRX) Fessi Hatem (Paris FRX) Devissaguet Jean-Philippe (Neuilly sur Seine FRX) Puisieux Francis (Maisons-Alfort FRX), Process for the preparation of dispersible colloidal systems of amphiphilic lipids in the form of oligolamellar liposome.
Cech Thomas R. (Boulder CO) Zaug Arthur J. (Louisville CO) Been Michael D. (Boulder CO), RNA ribozyme polymerases, dephosphorylases, restriction endoribo-nucleases and methods.
Hirosue Sachiko ; Mueller Bernhard G.,CHX ; Langer Robert S. ; Mulligan Richard C., Sub-100nm biodegradable polymer spheres capable of transporting and releasing nucleic acids.
Larry Gold ; Michael Willis ; Tad Koch ; Steven Ringquist ; Kirk Jensen ; Brent Atkinson, Systematic evolution of ligands by exponential enrichment: photoselection of nucleic acid ligands.
Gold Larry ; Willis Michael ; Koch Tad ; Ringquist Steven ; Jensen Kirk ; Atkinson Brent, Systematic evolution of ligands by exponential enrichment: photoselection of nucleic acid ligands and solution selex.
Gold Larry ; Willis Michael ; Koch Tad ; Ringquist Steven ; Jensen Kirk ; Atkinson Brent, Systematic evolution of ligands by exponential enrichment: photoselection of nucleic acid ligands and solution selex.
Kunz Lawrence L. ; Klein Richard A. ; Reno John M. ; Grainger David J.,GBX ; Metcalfe James C.,GBX ; Weissberg Peter L.,GBX ; Anderson Peter G., Therapeutic inhibitor of vascular smooth muscle cells.
Setterstrom, Jean A.; Tice, Thomas R.; Jacob, Elliot; Reid, Robert H.; van Hamont, John; Boedecker, Edgar C.; Jeyanthi, Ramassubbu; Friden, Phil; Roberts, F. Donald; McQueen, Charles E.; Bhattacharje, Therapeutic treatment and prevention of infections with a bioactive material(s) encapuslated within a biodegradable-bio-compatable polymeric matrix.
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