IP Library Granted Patent US 12,186,410
Granted Patent B2
US 12,186,410 · App. 17/234,323 · Granted Jan 7, 2025

Bi-dota complex-loaded dendritic polymer nanoparticles

Inventors: Jesus Manuel Perez (Orlando, FL); Santimukul Santra (Orlando, FL)
Assignee: University of Central Florida Research Foundation, Inc.
A61K51/065A61K31/519A61K49/0423A61P35/00C08G63/6882C08G83/002
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Quick Facts
Patent No.
US 12,186,410
App. No.
17/234,323
Granted
Jan 7, 2025
Kind
B2
Abstract

Disclosed are compositions comprising polymeric nanoparticles and methods of using the same. The polymeric nanoparticles can be conjugated with a targeting ligand that is a substrate for a solid tumor-specific cell protein. The polymeric nanoparticles can also comprises an imaging compound and/or a therapeutic agent encapsulated in the hydrophobic interior of the nanoparticle. A cancer therapeutic composition comprising the nanoparticle is also disclosed. The disclosed nanoparticles can be used to target and deliver imaging and/or therapeutic compounds to cancer cells, thereby identifying and/or treating a solid tumor cell target. Methods for treating cancer, such as lung cancer, using the polymeric nanoparticles are also disclosed.

Claims (18)

1. A method of identifying a solid tumor cell target, comprising,

1) contacting a cell with an effective amount of a composition comprising at least one polymeric nanoparticle conjugated with a targeting ligand that is a substrate for a solid tumor-specific cell protein, wherein the nanoparticle further comprises an imaging compound and an anti-cancer agent; wherein the polymeric nanoparticle comprises a hyperbranched polyester and/or polyamide polymer, wherein the hyperbranched polyester and/or polyamide polymer has the formula:

wherein A is a heteroatom independently selected from nitrogen and oxygen; R 1 and R 2 are independently selected from hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, and substituted or unsubstituted alkynyl; 1 is an integer from 1 to 5; m is 0, 1, or 2; n is an integer from 1 to 5; and o is an integer from 2 or greater;

2) identifying one or more nanoparticles bound to the cells by using imaging devices; and optionally,

3) monitoring the solid tumor cell target by repeating 1) and 2).

2. The method of claim 1 , further comprising treating the solid tumor cell by killing or inhibiting its growth.

3. The method of claim 1 , wherein the solid tumor cell is a prostate cancer cell, a breast cancer cell, a colon cancer cell, a pancreas cancer cell, or a lung cancer cell.

4. The method of claim 1 , wherein the nanoparticle further comprises, in its hydrophobic interior, a therapeutic agent.

5. The method of claim 1 , wherein the polymeric nanoparticle is biodegradable.

6. The method of claim 1 , wherein the polymeric nanoparticle has one or more internal hydrophobic pockets and a hydrophilic outer surface.

7. The method of claim 1 , wherein the polymeric nanoparticle further comprises a hydrophobic near-infrared fluorescent dye encapsulated therein.

8. The method of claim 4 , further comprising a fluorescent dye co-encapsulated with said therapeutic agent.

9. The method of claim 1 , wherein the polymeric nanoparticle further comprises one or more imaging compounds encapsulated therein.

10. The method of claim 1 , wherein the polymeric nanoparticle further comprises a X-ray, MRI, or PET detectable compound.

11. The method of claim 1 , wherein the polymeric nanoparticle further comprises a metal compound comprising Au, Ag, Pd, Pt, Cu, Ni, Co, Fe, Mn, Ru, Rh, Os, or Ir.

12. The method of claim 1 , wherein the polymeric nanoparticle further comprises a radionuclide comprising 90 Y, 177 Lu, 18 F, 64 Cu, 67 Cu, 89 Zr, 111 In, 124 I, 123 I, 99 mTc, 225 Ac, 57 La, 67/69 Ga, 68 Ga, or 152 Eu.

13. The method of claim 1 , wherein the polymeric nanoparticle is conjugated or chelated to DOTA (1,4,7,10-tetraazacyclo-dodecane-1,4,7,10-tetraacetic acid), DTPA (diethylene triamine pentaacetic acid), DOTP (1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetra (methylene phosphonic) acid), DOTMA, (1R, 4R, 7R, 10R)-α′α″α′″-Tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetraacetic acid) tetrasodium salt, TETA, (1,4,8,11-Tetraazacyclotetradecane-1,4,8, 11-tetraacetic acid), DOTAM (1,4,7,10-Tetrakis (carbamoylmethyl)-1,4,7, 10-tetraazacyclododecane), CB-TE2A (1,4,8,11-tetraazabicyclo[6.6.2]hexadecane-4, 11-dicetic acid), and NOTA ((1,4,7-triazacyclononane-N,N′,N″-triacetic acid).

14. The method of claim 1 , wherein the polymeric nanoparticle further comprises a folate.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 16, 2021
From: PEREZ, JESUS MANUEL; SANTRA, SANTIMUKUL
To: UNIVERSITY OF CENTRAL FLORIDA RESEARCH FOUNDATION, INC.
Reel/Frame 056876/0449 →
Continuity (3)
Division 16317757
Provisional Application 62362323 · Jul 14, 2016
Related Publication 20210236665A1 · Aug 5, 2021
References Cited (200)
US 6444758B2 · McNamara et al. · 2002 [cited by applicant]
US 8337813B2 · Schultz et al. · 2012 [cited by applicant]
US 8372944B1 · Perez et al. · 2013 [cited by applicant]
US 20070258907A1 · Davis · 2007 [cited by applicant]
US 20080112891A1 · Tomalia · 2008 [cited by examiner]
US 20110159113A1 · Adeli et al. · 2011 [cited by applicant]
US 20110286919A1 · Joshi et al. · 2011 [cited by applicant]
US 20140010879A1 · Shen et al. · 2014 [cited by applicant]
US 20140044648A1 · Perez et al. · 2014 [cited by applicant]
US 20140178300A1 · Pomper et al. · 2014 [cited by applicant]
US 20140243664A1 · El-Sayed et al. · 2014 [cited by applicant]
US 20140248210A1 · Bradbury et al. · 2014 [cited by applicant]
US 20140255299A1 · Khaled et al. · 2014 [cited by applicant]
US 20150004103A1 · Borbely et al. · 2015 [cited by applicant]
US 20150104387A1 · Pomper et al. · 2015 [cited by applicant]
US 20150284507A1 · Perez et al. · 2015 [cited by applicant]
IN 664MUM2006 · 2007 [cited by applicant]
WO 2016176462 · 2016 [cited by applicant]
Santra et al., Molecular Pharmaceutics, 2010, 7(4), p. 1209-1222. (Year: 2010). [cited by examiner]
Thompson et al., https://digitalcommons.pittstate.edu/posters_2015/8/, Apr. 8, 2015. (Year: 2015). [cited by examiner]
Han et al., Langmuir, 2013, 29, p. 8402-8409. (Year: 2013). [cited by examiner]
Lee et al., Chem. Soc. Rev., 2012, 41, p. 2656-2672. (Year: 2012). [cited by examiner]
Flores-Fernandez, 2015, Electronic Theses and Dissertations. 5008. (Year: 2015). [cited by examiner]
Motoyama et al., The AAPS Journal, 2014, 16(6), p. 1298-1308. (Year: 2014). [cited by examiner]
Heckert et al., ACS Macro Lett., 2017, 6, p. 235-240. (Year: 2017). [cited by examiner]
Addison Ault. (1998) Techniques and Eperiments for Organic Chem., Sixth Edition, pp. 48-50, 53-55, 60, 130-131. [cited by applicant]
Aime S, et al. (2002) Insights into the use of paramagnetic Gd(III) complexes in MR-molecular imaging investigations. J. Magn. Reson. Imaging. 16: 394-406. [cited by applicant]
Aime S, et al. (2009) Pushing the sensitivity envelope of lanthanide-based magnetic resonance imaging (MRI) contrast agents for molecular imaging applications. Acc. Chem. Res. 42: 822-831. [cited by applicant]
Allen MJ, et al. (2004) Cellular delivery of MRI contrast agents. Chemistry & Biology. 11: 301-307. [cited by applicant]
Anderson EA, et al. (2006) Viral nanoparticles donning a paramagnetic coat: conjugation of MRI contrast agents to the MS2 capsid. Nano Lett. 6: 1160-1164. [cited by applicant]
Anton, N.et al., (2014) Nanotechnology for computed tomography: a real potential recently disclosed. Pharmaceutical research, 31, 20-34. [cited by applicant]
Asati A, et al. (2009) Oxidase-like activity of polymer-coated cerium oxide nanoparticles. Angew. Chem. Int. Ed. Engl. 48: 2308-2312. [cited by applicant]
Asati A, et al. (2010) Surface-charge-dependent cell localization and cytotoxicity of cerium oxide nanoparticles. ACS Nano. 4: 5321-5331. [cited by applicant]
Attia, M. F, et al. (2014). Biodistribution of X-ray iodinated contrast agent in nano-emulsions is controlled by the chemical nature of the oily core. ACS nano, 8(10), 10537-10550. [cited by applicant]
Bachovchin, D. A., et al., (2009) Identification of selective inhibitors of uncharacterized enzymes by high-throughput screening with fluorescent activity-based probes. Nature biotechnology, 27, 387-94. [cited by applicant]
Bae KH, et al. (2010) Bioinspired Synthesis and Characterization of Gadolinium-Labeled Magnetite Nanoparticles for Dual Contrast T(1)- and T(2)-Weighted Magnetic Resonance Imaging. Bioconjugate Chem. 21: 505-512. [cited by applicant]
Barrett, J.A. et al. (2013) First-in-man evaluation of 2 high-affinity PSMA-avid small molecules for imaging prostate cancer. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 54, 380-387. [cited by applicant]
Baskin, J.M. et al. (2007) Copper-free click chemistry for dynamic in vivo imaging. Proceedings of the National Academy of Sciences of the United States of America 104, 16793-16797. [cited by applicant]
Beck, T.; et al., (2008) 5-Amino-2,4,6-triiodo-isophthalic acid monohydrate. Acta crystallographica. Section E, Structure reports online, 64, 01286. [cited by applicant]
Boal, A. K. et al., (2000) Self-assembly of nanoparticles into structured spherical and network aggregates. Nature, 404, 746-8. [cited by applicant]
Boohaker, R.J. et al. (2012) Rational Development of a Cytotoxic Peptide to Trigger Cell Death. Molecular pharmaceutics 9:7, 2080-2093. [cited by applicant]
Boohaker, R.J., et al., (2012) The use of therapeutic peptides to target and to kill cancer cells. Current medicinal chemistry 19, 3794-3804. [cited by applicant]
Bostwick, et al., (1998) Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. Cancer 82, 2256-2261. [cited by applicant]
Brekke C, et al. (2007) The in vitro effects of a bimodal contrast agent on cellular functions and relaxometry. NMR in Biomed. 20: 77-89. [cited by applicant]
Bull SR, et al. (2005) Magnetic resonance imaging of self-assembled biomaterial scaffolds. Bioconjugate Chem. 16: 1343-1348. [cited by applicant]
Bull SR, et al. (2005) Self-assembled peptide amphiphile nanofibers conjugated to MRI contrast agents. Nano Lett. 5: 1-4. [cited by applicant]
Cancer Facts and Figures (2009). American Cancer Society, 72 pages. [cited by applicant]
Caravan P, et al. (1999) Gadolinium (III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications. Chem. Rev. 99: 2293-2352. [cited by applicant]
Caravan P, et al. (2002) The interaction of MS-325 with human serum albumin and its effect on proton relaxation rates. J. Am. Chem. Soc. 124: 3152-3162. [cited by applicant]
Caravan P. (2006) Strategies for increasing the sensitivity of gadolinium-based MRI contrast agents. Chem. Soc. Rev. 35: 512-523. [cited by applicant]
Chanda, N, et al., (2010) Bombesin functionalized gold nanoparticles show in vitro and in vivo cancer receptor specificity. Proceedings of the National Academy of Sciences of the United States of America, 107, 8760-5. [cited by applicant]
Chang, S.S. et al. (1999) Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. Cancer research 59, 3192-3198. [cited by applicant]
Chen T, et al. (2011) Smart multifunctional nanostructure for targeted cancer chemotherapy and magnetic resonance imaging. ACS Nano. 5: 7866-7873. [cited by applicant]
Chen, Y. et al. (2008) Radiohalogenated prostate-specific membrane antigen (PSMA)-based ureas as imaging agents for prostate cancer. J Med Chem 51, 7933-7943. [cited by applicant]
Chen, Y. et al. (2012) Synthesis and biological evaluation of low molecular weight fluorescent imaging agents for the prostate-specific membrane antigen. Bioconjugate chemistry 23, 2377-2385. [cited by applicant]
Cheng Z, et al. (2010) Gadolinium-conjugated dendrimer nanoclusters as a tumor targeted T1 magnetic resonance imaging contrast agent. Angew. Chem. Int. Ed. Engl. 49: 346-350. [cited by applicant]
Cheng ZL, et al. (2009) Porous polymersomes with encapsulated Gd-labeled dendrimers as highly efficient MRI contrast agents. Adv. Funct. Mater. 19: 3753-3759. [cited by applicant]
Cheng, J. et al. (2007) Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery. Biomaterials 28, 869-876. [cited by applicant]
Cheon, J, et al., (2008) Synergistically integrated nanoparticles as multimodal probes for nanobiotechnology. Accounts of chemical research, 41, 1630-40. [cited by applicant]
Cho SJ, et al. (2006) Gold-coated iron nanoparticles: a novel magnetic resonance agent for T-1 and T-2 weighted imaging. Nanotechnology. 17: 640-644. [cited by applicant]
Crich SG, et al. (2004) Improved route for the visualization of stem cells labeled with a Gd-/Euchelate as dual (MRI and fluorescence) agent. Magn. Reson. Med. 51: 938-944. [cited by applicant]
Datta A, et al. (2008) High relaxivity gadolinium hydroxypyridonate-viral capsid conjugates: nanosized MRI contrast agents. J. Am. Chem. Soc. 130: 2546-2552. [cited by applicant]
Davis, M. E. et al., (2008) Nanoparticle therapeutics: an emerging treatment modality for cancer. Nature reviews. Drug discovery, 7, 771-82. [cited by applicant]
DeKrafft, et al., (2009) Iodinated nanoscale coordination polymers as potential contrast agents for computed tomography. Angewandte Chemie, 48, 9901-4. [cited by applicant]
Desai, S.P., et al., (2013) Mitochondrial localization and the persistent migration of epithelial cancer cells. Biophysical journal 104, 2077-2088. [cited by applicant]
Drake P, et al. (2007) Gd-doped iron-oxide nanoparticles for tumour therapy via magnetic field hyperthermia. J. Mater. Chem. 17: 4914-4918. [cited by applicant]
Duimstra JA, et al. (2005) A gadolinium chelate for detection of beta- glucuronidase: a self-immolative approach. J. Am. Chem. Soc. 127: 12847-12855. [cited by applicant]
Eck, W. et al., (2010) Anti-CD4-targeted gold nanoparticles induce specific contrast enhancement of peripheral lymph nodes in X-ray computed tomography of live mice. Nano letters, 10, 2318-22. [cited by applicant]
Endres PJ, et al. (2008) Cell-permeable MR contrast agents with increased intracellular retention. Bioconjugate Chem. 19: 2049-2059. [cited by applicant]
Farokhzad, O.C. et al. (2004) Nanoparticle-aptamer bioconjugates: a new approach for targeting prostate cancer cells. Cancer research 64, 7668-7672. [cited by applicant]
Farokhzad, O.C. et al. (2006) Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proceedings of the National Academy of Sciences of the United States of America 103, 6315-6320. [cited by applicant]
Fonseca, C. et al., (2002) Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity. Journal of controlled release, 83, 273-286. [cited by applicant]
Freeman, L.M. et al. (2002). The role of (111) in Capromab Pendetide (Prosta-ScintR) immunoscintigraphy in the management of prostate cancer. Q J Nucl Med 46, 131-137. [cited by applicant]
Frullano L, et al. (2006) Synthesis and characterization of a doxorubicin-Gd(III) contrast agent conjugate: a new approach toward prodrug-procontrast complexes. Inorg. Chem. 45: 8489-8491. [cited by applicant]
Frullano L, et al. (2007) Multimodal MRI contrast agents. J. Biol. Inorg. Chem. 12: 939-949. [cited by applicant]
Garg, P., et al., (2013). Transmembrane pore formation by the carboxyl terminus of Bax protein. Biochimica et biophysica acta 1828, 732-742. [cited by applicant]
Ghosh, A. et al.., (2004) Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem 91, 528-539. [cited by applicant]
Gupte, A. et al., (2004) Formulation and characterization of Paclitaxel, 5-FU and Paclitaxel + 5-FU microspheres. International journal of pharmaceutics, 276, 93-106. [cited by applicant]
Hainfeld, J. F. et al., (2006) Gold nanoparticles: a new X-ray contrast agent. The British journal of radiology, 79, 248-53. [cited by applicant]
Haseman, et al., (2000) Pendetide imaging of prostate cancer. Cancer Biother Radiopharm 15, 131-140. [cited by applicant]
Hattori, Y. et al., (2005) Folate-linked nanoparticle-mediated suicide gene therapy in human prostate cancer and nasopharyngeal cancer with herpes simplex virus thymidine kinase. Cancer Gene Ther 12, 796-809. [cited by applicant]
Haun JB, et al. (2011) Micro-NMR for Rapid Molecular Analysis of Human Tumor Samples. Sci.Trans. Med. 3: 71ra16. [cited by applicant]
Holland, J.P. et al. (2010) Measuring the pharmacodynamic effects of a novel Hsp90 inhibitor on HER2/neu expression in mice using Zr-DFO-trastuzumab. PLoS One 5, e8859. [cited by applicant]
Hooker JM, et al. (2007) Magnetic resonance contrast agents from viral capsid shells: a comparison of exterior and interior cargo strategies. Nano Lett. 7: 2207-2210. [cited by applicant]
Horoszewicz, J.S., (1987) Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients. Anticancer Res 7, 927-935. [cited by applicant]
Hrkach, J. et al. (2012) Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile. Science translational medicine 4, 128ra139. [cited by applicant]
Hu F, et al. (2010) Highly dispersible, superparamagnetic magnetite nanoflowers for magnetic resonance imaging. Chem. Commun. 46:73-75. [cited by applicant]
Hu, X, et al (2004) Advances in high-field magnetic resonance imaging. Ann. Rev. Biomed. Eng. 6: 157-184. [cited by applicant]
Huber MM, et al. (1998) Fluorescently detectable magnetic resonance imaging agents. Bioconjug. Chem. 9: 242-249. [cited by applicant]
International Preliminary Report on Patentability issued for Application No. PCT/US2017/042145, dated Jan. 24, 2019, 7 pages. [cited by applicant]
International Preliminary Report on Patentability issued for International Application No. PCT/US2016/029804, dated Nov. 9, 2017. [cited by applicant]
International Search Report and Written Opinion issued for International Application No. PCT/US2016/029804, dated Aug. 25, 2016. [cited by applicant]
Israeli, R.S., et al., (1993). Molecular cloning of a complementary DNA encoding a prostate-specific membrane antigen. Cancer research 53, 227-230. [cited by applicant]
Iyer, et al., (2009) Self-healing colloidal crystals. Angewandte Chemie, 48, 4562-6. [cited by applicant]
Jakhmola, A, et al., (2014) Poly-epsilon-caprolactone tungsten oxide nanoparticles as a contrast agent for X-ray computed tomography. Biomaterials, 35, 2981-6. [cited by applicant]
Jakhmola, A, et al., (2012) Inorganic nanoparticles based contrast agents for X-ray computed tomography. Advanced healthcare materials, 1, 413-31. [cited by applicant]
Jayakannan, M., and S. Ramakrishnan. (2002) “Preparation of polyethers via proton acid catalyzed transetherification reactions.” Macromolecular Chemistry and Physics 201:7, 759-767. [cited by applicant]
Josephson L, et al. (1999) High-efficiency intracellular magnetic labeling with novel superparamagnetic-Tat peptide conjugates. Bioconjugate Chem. 10: 186-191. [cited by applicant]
Kaittanis C, et al. (2009) The Role of nanoparticle valency in the nondestructive magnetic-relaxation-mediated detection and magnetic isolation of cells m complex media. J. Am. Chem. Soc. 131: 12780-12791. [cited by applicant]
Kaittanis C, et al. (2011) The assembly state between magnetic nanosensors and their targets orchestrates their magnetic relaxation response. J. Am. Chem. Soc. 133: 3668-3676. [cited by applicant]
Kaittanis C, et al. (2012) Rapid and sensitive detection of an intracellular pathogen in human peripheral leukocytes with hybridizing magnetic relaxation nanosensors. PloS One 7: e35326. [cited by applicant]
Kalman FK, et al. (2007) Potentiometric and relaxometric properties of a gadolinium-based MRI contrast agent for sensing tissue pH. Inorg. Chem. 46: 5260-5270. [cited by applicant]
Kattumuri, V., (2007) Gum arabic as a phytochemical construct for the stabilization of gold nanoparticles: in vivo pharmacokinetics and X-ray-contrast-imaging studies. Small, 3, 333-41. [cited by applicant]
Kim HM, et al. (2011) Synthesis and high performance of magnetofluorescent polyelectrolyte nanocomposites as MR/near-infrared multimodal cellular imaging nanoprobes. ACS Nano. 5: 8230-8240. [cited by applicant]
Kim, C. K. (2009) Entrapment of hydrophobic drugs in nanoparticle monolayers with efficient release into cancer cells. Journal of the American Chemical Society, 131, 1360-1. [cited by applicant]
Kim, D. et al., (2007) Antibiofouling polymer-coated gold nanoparticles as a contrast agent for in vivo X-ray computed tomography imaging. Journal of the American Chemical Society, 129, 7661-5. [cited by applicant]
Kim, T. et al., (2011) Mesoporous silica-coated hollow manganese oxide nanoparticles as positive T1 contrast agents for labeling and MRI tracking of adipose-derived mesenchymal stem cells. Journal of the American Chemic… [cited by applicant]
Kiss, T. & Farkas, E. (1998) Metal-binding ability of desferrioxamine B. Journal of Inclusion Phenomena and Molecular Recognition in Chemistry 32, 385-403. [cited by applicant]
Kolb, H. C. et al., (2001) Click Chemistry: Diverse Chemical Function from a Few Good Reactions. Angewandte Chemie, 40, 2004-2021. [cited by applicant]
Lattuada L, et al. (2003) Synthesis of Gd-DTPA-cholesterol: a new lipophilic gadolinium complex as a potential MRI contrast agent. Tetrahedron Lett. 44: 3893-3895. [cited by applicant]
Laurent S, et al. (2008) Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem. Rev. 108: 2064-2110. [cited by applicant]
Lee J, et al. (2007) Rational design, synthesis, and biological evaluation of progesterone-modified MRI contrast agents. Chemistry & Biology 14: 824-834. [cited by applicant]
Leibowitz-Amit, R. & Joshua, A.M. (2012) Targeting the androgen receptor in the management of castration-resistant prostate cancer: rationale, progress, and future directions. Curr Oncol 19, S22-31. [cited by applicant]
Leibowitz-Amit, (2013) The changing landscape in metastatic castration-resistant prostate cancer. Current opinion in supportive and palliative care 7, 243-248. [cited by applicant]
Li, X. et al., (2014) Contrast agents for preclinical targeted X-ray imaging. Advanced drug delivery reviews, 76, 116-33. [cited by applicant]
Li, X. et al., (2013) Iodinated alpha-tocopherol nano-emulsions as non-toxic contrast agents for preclinical X-ray imaging. Biomaterials, 34, 481-91. [cited by applicant]
Liu, Y. (2012) Nanoparticulate X-ray computed tomography contrast agents: from design validation to in vivo applications. Accounts of chemical research, 45, 1817-27. [cited by applicant]
Lopes, A.O. et al., (1990) and pharmacokinetic characterization of the site-specific immunoconjugate CYT-356 derived from antiprostate monoclonal antibody 7E11-C5. Cancer research 50, 6423-6429. [cited by applicant]
Louie A. (2010) Multimodality imaging probes: design and challenges. Chem. Rev. 110: 3146-3195. [cited by applicant]
Louie AY, et al. (2000) In vivo visualization of gene expression using magnetic resonance imaging. Nat. Biotechnol. 18: 321-325. [cited by applicant]
Major JL, et al. (2009) Bioresponsive, cell-penetrating, and multimeric MR contrast agents. Acc. Chem. Res. 42: 893-903. [cited by applicant]
Major JL, et al. (2007) The synthesis and in vitro testing of a zinc-activated MRI contrast agent. Proc. Natl. Acad. Sci. U.S.A. 104: 13881-13886. [cited by applicant]
Malmstroem, (1995) Hyperbranched Aliphatic Polyesters., Macromolecules 28 (5), 1698-1703. DOI: 10.1021/ma00109a049. [cited by applicant]
Manus LM, et al. (2010) Gd(III)-nanodiamond conjugates for MRI contrast enhancement. Nano Lett. 10: 484-489. [cited by applicant]
Mastarone DJ, et al. (2011) A modular system for the synthesis of multiplexed magnetic resonance probes. J. Am. Chem. Soc. 133: 5329-5337. [cited by applicant]
Mazooz G, et al. (2005) Development of magnetic resonance imaging contrast material for in vivo mapping of tissue transglutaminase activity. Cancer Res. 65: 1369-1375. [cited by applicant]
McCarthy JR, et al. (2005) Polymeric nanoparticle preparation that eradicates tumors. Nano Lett. 5: 2552-2556. [cited by applicant]
McDevitt, M.R. et al. (2000) An alpha-particle emitting antibody ([213Bi]J591) for radioimmunotherapy of prostate cancer. Cancer research 60, 6095-6100. [cited by applicant]
Meijs, W.E. et al. (1997) Zirconium-labeled monoclonal antibodies and their distribution in tumor-bearing nude mice. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 38, 112-118. [cited by applicant]
Milowsky, M.I. et al. (2007) Vascular targeted therapy with anti-prostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors. J Clin Oncol 25, 540-547. [cited by applicant]
Morris, M.J. et al. (2007) Phase I evaluation of J591 as a vascular targeting agent in progressive solid tumors. Clinical cancer research: an official journal of the American Association for Cancer Research 13, 2707-271… [cited by applicant]
Mulder WJ, et al.(2004) A liposomal system for contrast-enhanced magnetic resonance imaging of molecular targets. Bioconjugate Chem. 15: 799-806. [cited by applicant]
Nayak, S. et al., (2004) Folate-mediated cell targeting and cytotoxicity using thermoresponsive microgels. Journal of the American Chemical Society, 126, 10258-9. [cited by applicant]
Nayak, S.; Lyon, L. A. (2005) Soft nanotechnology with soft nanoparticles. Angewandte Chemie, 44, 7686-708. [cited by applicant]
Nelson, M. E. (2004) 2-amino-O4-benzylpteridine derivatives: potent inactivators of O6-alkylguanine-DNA alkyltransferase. Journal of medicinal chemistry, 47, 3887-91. [cited by applicant]
Oh, et al., (2011) Large-scale synthesis of bioinert tantalum oxide nanoparticles for X-ray computed tomography imaging and bimodal image-guided sentinel lymph node mapping. Journal of the American Chemical Society, 133… [cited by applicant]
Packard, et al., (1985) Fluorescence lifetimes of carbocyanine lipid analogues in phospholipid bilayers. Biochemistry, 24, 5176-81. [cited by applicant]
Pan D, et al. (2008) Ligand-directed nanobialys as theranostic agent for drug delivery and manganese-based magnetic resonance imaging of vascular targets. J. Am. Chem. Soc. 130: 9186-9187. [cited by applicant]
Paquet C, et al. (2011) Clusters of superparamagnetic iron oxide nanoparticles encapsulated in a hydrogel: a particle architecture generating a synergistic enhancement of the T2 relaxation. ACS Nano. S: 3104-3112. [cited by applicant]
Parker, N. et al., (2005) Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. Analytical biochemistry, 338, 284-93. [cited by applicant]
Perez JM, et al. (2002) Magnetic relaxation switches capable of sensing molecular interactions. Nat. Biotechnol. 20: 816-820. [cited by applicant]
Perez JM, et al. (2008) Synthesis of biocompatible dextrancoated nanoceria with pH-dependent antioxidant properties. Small. 4: SS2-SS6. [cited by applicant]
Perez, J.M., et al., (2004) Use of magnetic nanoparticles as nanosensors to probe for molecular interactions. Chembiochem: a European journal of chemical biology 5, 261-264. [cited by applicant]
Perez, J.M., (2002) DNA-based magnetic nanoparticle assembly acts as a magnetic relaxation nanoswitch allowing screening of DNA-cleaving agents. Journal of the American Chemical Society 124, 2856-2857. [cited by applicant]
Perez, J.M., (2003) Viral-induced self-assembly of magnetic nanoparticles allows the detection of viral particles in biological media. Journal of the American Chemical Society 125, 10192-10193. [cited by applicant]
Poselt E, et al. (2012) Relaxivity Optimization of a PEGylated Iron-Oxide-Based Negative Magnetic Resonance Contrast Agent for T(2)-Weighted Spin-Echo Imaging. ACS Nano 6: 1619-1624. [cited by applicant]
Rabin, O., et al., (2006) An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles. Nature materials, 5, 118-22. [cited by applicant]
Rafehi, H. et al. (2011) Clonogenic assay: adherent cells. Journal of visualized experiments: JoVE 49, 2573. [cited by applicant]
Ratts, R. et al. (2003) The cytosolic entry of diphtheria toxin catalytic domain requires a host cell cytosolic translocation factor complex. The Journal of cell biology 160, 1139-1150. [cited by applicant]
Ross, J.S. et al. (2003) Correlation of primary tumor prostate-specific membrane antigen expression with disease recurrence in prostate cancer. Clinical cancer research: an official journal of the American Association f… [cited by applicant]
Ruggiero, A. et al. (2011) Targeting the Internal Epitope of Prostate-Specific Membrane Antigen with 89Zr-7E11 Immuno-PET. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 52, 1608-1615. [cited by applicant]
Santra S, et al. (2009) Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging. Small S: 1862-1868. [cited by applicant]
Santra S; et al. (2010) Aliphatic hyperbranched polyester: a new building block in the construction of multifunctional nanoparticles and nanocomposites. Langmuir 26: 5364-5373. [cited by applicant]
Santra, S. et al., (2011) Selective N-Alkylation of beta-Alanine Facilitates the Synthesis of a Poly (amino acid)-Based Theranostic Nanoagent. Biomacromolecules 12:11, 3917-3927. [cited by applicant]
Santra, S., (2011) Cell-specific, activatable, and theranostic prodrug for dual-targeted cancer imaging and therapy. Journal of the American Chemical Society 133, 16680-16688. [cited by applicant]
Santra, Santimukul, and Anil Kumar. (2004) Facile synthesis of aliphatic hyperbranched polyesters based on diethyl malonate and their irreversible molecular encapsulation. Chemical Communications 18, 2126-2127. [cited by applicant]
Scatena, C.D. et al. (2004) Imaging of bioluminescent LNCaP-luc-M6 tumors: a new animal model for the study of metastatic human prostate cancer. The Prostate 59, 292-303. [cited by applicant]
Schrecengost, R. & Knudsen, K.E. (2013) Molecular pathogenesis and progression of prostate cancer. Seminars in oncology 40, 244-258. [cited by applicant]
Schwenzer, N. F. (2009) Non-invasive assessment and quantification of liver steatosis by ultrasound, computed tomography and magnetic resonance. Journal of hepatology, 51, 433-45. [cited by applicant]
Silver, D.A., et al., (1997) Prostate-specific membrane antigen expression in normal and malignant human tissues. Clinical cancer research: an official journal of the American Association for Cancer Research 3, 81-85. [cited by applicant]
Singh, M. P. et al., (2012) Development of iron-doped silicon nanoparticles as bimodal imaging agents. ACS nano, 6, 5596-604. [cited by applicant]
Smith-Jones, P.M. et al. (2003) Radiolabeled monoclonal antibodies specific to the extracellular domain of prostate-specific membrane antigen: preclinical studies in nude mice bearing LNCaP human prostate tumor. Journal… [cited by applicant]
Song Y, et al. (2008) Synthesis of multimeric MR contrastagents for cellular imaging. J. Am. Chem. Soc. 130: 6662-6663. [cited by applicant]
Song Y, etal. (2009) Multimodal gadolinium-enriched DNA-gold nanoparticle conjugates for cellular imaging. Angew. Chem. Int. Ed. Engl. 48: 9143-9147. [cited by applicant]
Song Y, et al (2010) Synthesis and characterization of new porphyrazine-Gd(III) conjugates as multimodal MR contrast agents. Bioconjugate Chem. 21:2267-227S. [cited by applicant]
Soriano Del Amo, D. et al. (2010) Biocompatible copper(I) catalysts for in vivo imaging of glycans. Journal of the American Chemical Society 132, 16893-16899. [cited by applicant]
Stern, S.T., Adiseshaiah, P.P. & Crist, R.M. (2012) Autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity. Particle and fibre toxicology 9, 20, 17 pages. [cited by applicant]
Sun EY, et al., (2006) “Clickable” nanoparticles for targeted imaging. Mol. Imaging. S: 122-128. [cited by applicant]
Tatulian, S.A., et al. (2012) Molecular basis for membrane pore formation by Bax protein carboxyl terminus. Biochemistry 51, 9406-9419. [cited by applicant]
Tolaney, S.M., et al., (2008) Lymphopenia associated with adjuvant anthracycline/taxane regimens. Clinical breast cancer 8, 352-356. [cited by applicant]
Tromsdorf UI, et al. (2007) Size and surface effects on the MRI relaxivity of manganese ferrite nanoparticle contrast agents. Nano Lett. 7: 2422-2427. [cited by applicant]
Tu C, et al. (2011) Activatable T 1 and T2 magnetic resonance imaging contrast agents. Ann. Biomed. Eng. 39: 1335-1348. [cited by applicant]
Tu C, et al. (2011) Receptor-targeted iron oxide nanoparticles for molecular MR imaging of inflamed atherosclerotic plaques. Biomaterials. 32: 7209-7216. [cited by applicant]
Tu CQ, et al.(2007) Photochromically-controlled, reversibly-activated MRI and optical contrast agent. Chem. Commun. 13: 1331-1333. [cited by applicant]
Ulmert, D. et al. (2012) Imaging androgen receptor signaling with a radiotracer targeting free prostate-specific antigen. Cancer discovery 2, 320-327. [cited by applicant]
Urbanczyk-Pearson LM, et al. (2008) Preparation of magnetic resonance contrast agents activated by beta-galactosidase. Nat. Protoc. 3: 341-350. [cited by applicant]
Uzgiris EE, et al. (2004) Conformation and structure of polymeric contrast agents for medical imaging. Biomacromolecules. 5: 54-61. [cited by applicant]
Van der Meel, et al., (2013) Ligand-targeted particulate nanomedicines undergoing clinical evaluation: current status. Advanced drug delivery reviews 65, 1284-1298. [cited by applicant]
Verel, I. et al. (2003) 89Zr immuno-PET: comprehensive procedures for the production of 89Zr-labeled monoclonal antibodies. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 44, 1271-1281. [cited by applicant]
Weinmann HJ, et al. (1984) Characteristics of gadolinium-DTPA complex: a potential NMR contrast agent. AJR Am. J. Roentgenol. 142: 619-624. [cited by applicant]
Wesche, J. et al. (2006) FGF-1 and FGF-2 require the cytosolic chaperone Hsp90 for translocation into the cytosol and the cell nucleus. The Journal of biological chemistry 281, 11405-11412. [cited by applicant]
Whitesides, G. M. et al., (2002) Self-assembly at all scales. Science, 295, 2418-21. [cited by applicant]
Whitesides, G. M. e al., (1991) Molecular self-assembly and nanochemistry: a chemical strategy for the synthesis of nanostructures. Science, 254, 1312-9. [cited by applicant]
Winter PM, et al. (2006) Molecular imaging by MRI. Curr. Cardio. Reports. 8: 65-69. [cited by applicant]
Wright, G.L., Jr. et al. (1996) Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy. Urology 48, 326-334. [cited by applicant]
Xu, L., et al., (2001) Tumor-targeted p53-gene therapy enhances the efficacy of conventional chemo/radiotherapy. J Control Release 74, 115-128. [cited by applicant]
Yang H, et al. (2011) Targeted dual-contrast T1- and T2-weighted magnetic resonance 1magmg of tumors usmg multifunctional gadolinium-labeled superparamagnetic iron oxide nanoparticles. Biomaterials. 32: 4584-4593. [cited by applicant]
Yao, V. & Bacich, D.J. (2006) Prostate specific membrane antigen (PSMA) expression gives prostate cancer cells a growth advantage in a physiologically relevant folate environment in vitro. The Prostate 66, 867-875. [cited by applicant]
Yao, et al., (2010) Expression of prostate-specific membrane antigen (PSMA), increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the non-polyglutamated folate, folic acid. … [cited by applicant]
You, C. C. et al., (2007) Detection and identification of proteins using nanoparticle-fluorescent polymer ‘chemical nose’ sensors. Nature nanotechnology, 2, 318-23. [cited by applicant]
Yuan, H et al., (2008). Cellular uptake of solid lipid nanoparticles and cytotoxicity of encapsulated paclitaxel in A549 cancer cells. International journal of pharmaceutics, 348, 137-45. [cited by applicant]
Zhang XA, et al. (2007) Water-soluble porphyrins as a dual-function molecular imaging platform for MRI and fluorescence zinc sensing. Proc. Natl. Acad. Sci. U.S.A. 104: 10780-10785. [cited by applicant]
Zhang, S. (2003) Fabrication of novel biomaterials through molecular self- assembly. Nature biotechnology, 21, 1171-8. [cited by applicant]
Zhao, J. et al. (2013) Mitochondrial dynamics regulates migration and invasion of breast cancer cells. Oncogene 32, 4814-4824. [cited by applicant]
Zhao, et al., (2012_ Dual-Modal Tumor Imaging via Long-Circulating Biodegradable Core-Crosslinked Polymeric Micelles. ACS macro letters, 1, 150-153. [cited by applicant]
Zhang, Hongbin, et al. “Hyperbranched polyester hydrogels with controlled drug release and cell adhesion properties.” Biomacromolecules 14.5 (2013): 1299-1310. [cited by applicant]
Heckert et al., “Design and Synthesis of New Sulfur-Containing Hyperbranched Polymer and Theranostic Nanomaterials for Bimodal Imaging and Treatment of Cancer”, ACS Macro Letters, vol. 6, No. 3, Mar. 21, 2017, pp. 235-2… [cited by applicant]
International Search Report and Written Opinion. Application No. PCT/US2017/042145. Mailed Sep. 29, 2017 (9 pages). [cited by applicant]
Supplementary European Search Report for Application No. 17828533.4, dated Feb. 24, 2020. [cited by applicant]
Extended European Search Report issued for Application No. 21174204.4, dated Sep. 28, 2021, 26 pages. [cited by applicant]