Dendrimer-based nanoparticles for cancer therapy.

Recent work has suggested that nanoparticles in the form of dendrimers may be a keystone in the future of therapeutics. The field of oncology could soon be revolutionized by novel strategies for diagnosis and therapy employing dendrimer-based nanotherapeutics. Several aspects of cancer therapy would be involved. Diagnosis using imaging techniques such as MRI will be improved by the incorporation of dendrimers as advanced contrast agents. This might involve novel contrast agents targeted specifically to cancer cells. Dendrimers can also be being applied to a variety of cancer therapies to improve their safety and efficacy. A strategy, somewhat akin to the "Trojan horse," involves targeting anti-metabolite drugs via vitamins or hormones that tumors need for growth. Further applications of dendrimers in photodynamic therapy, boron neutron capture therapy, and gene therapy for cancer are being examined. This presentation will cover the fundamentals of research utilizing dendrimers for cancer diagnosis and therapy. An evaluation of this new technologies will detail what advantage dendrimer based therapeutics might have over conventional cancer drugs.

[1]  P. Alivisatos The use of nanocrystals in biological detection , 2004, Nature Biotechnology.

[2]  M. Shortreed,et al.  Utilization of lipophilic ionic additives in liquid polymer film optodes for selective anion activity measurements. , 1997, Analytical chemistry.

[3]  I. Majoros,et al.  Acetylation of Poly(amidoamine) Dendrimers , 2003 .

[4]  S. Rosenberg,et al.  Karnofsky Memorial Lecture. The immunotherapy and gene therapy of cancer. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  K. Culver,et al.  Clinical applications of gene therapy for cancer. , 1994, Clinical chemistry.

[6]  Thommey P. Thomas,et al.  Design and Function of a Dendrimer-Based Therapeutic Nanodevice Targeted to Tumor Cells Through the Folate Receptor , 2002, Pharmaceutical Research.

[7]  D. Tomalia,et al.  Core–Shell Tecto(dendrimers): I. Synthesis and Characterization of Saturated Shell Models , 2000 .

[8]  M. Dewhirst,et al.  Hyperthermia enables tumor-specific nanoparticle delivery: effect of particle size. , 2000, Cancer research.

[9]  N. Hylton,et al.  Evaluation of the effects of intravascular MR contrast media (gadolinium dendrimer) on 3D time of flight magnetic resonance angiography of the body , 1996, Journal of magnetic resonance imaging : JMRI.

[10]  R. Barth,et al.  Boronated starburst dendrimer-monoclonal antibody immunoconjugates: evaluation as a potential delivery system for neutron capture therapy. , 1994, Bioconjugate chemistry.

[11]  R. Corn,et al.  Synthesis and characterization of covalently linked single-stranded DNA oligonucleotide-dendron conjugates. , 2003, Bioconjugate chemistry.

[12]  M. Dewhirst,et al.  Characterization of the effect of hyperthermia on nanoparticle extravasation from tumor vasculature. , 2001, Cancer research.

[13]  P. Singh,et al.  Starburst dendrimers: enhanced performance and flexibility for immunoassays. , 1994, Clinical chemistry.

[14]  P C Lauterbur,et al.  Dendrimer‐based metal chelates: A new class of magnetic resonance imaging contrast agents , 1994, Magnetic resonance in medicine.

[15]  Christopher R Williams,et al.  Current dendrimer applications in cancer diagnosis and therapy. , 2008, Current topics in medicinal chemistry.

[16]  Bryant C Nelson,et al.  Solid-phase extraction-electrospray ionization mass spectrometry for the quantification of folate in human plasma or serum. , 2004, Analytical biochemistry.

[17]  Philip S Low,et al.  Folate-mediated delivery of macromolecular anticancer therapeutic agents. , 2002, Advanced drug delivery reviews.

[18]  Thommey P. Thomas,et al.  Synthesis and functional evaluation of DNA-assembled polyamidoamine dendrimer clusters for cancer cell-specific targeting. , 2005, Chemistry & biology.

[19]  Thommey P. Thomas,et al.  Nanoparticle targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer. , 2005, Cancer research.

[20]  Albert H. Soloway,et al.  Delivery of Boron-10 for Neutron Capture Therapy by Means of Monoclonal Antibody - Starburst Dendrimer Immunoconjugates , 1992 .

[21]  S. Rosenberg,et al.  Immunotherapy and gene therapy of cancer. , 1991, Advances in surgery.

[22]  J. Prieto,et al.  A blood–tumor barrier limits gene transfer to experimental liver cancer: the effect of vasoactive compounds , 2000, Gene Therapy.

[23]  Donald A. Tomalia,et al.  Designed Dendrimer Syntheses by Self-Assembly of Single-Site, ssDNA Functionalized Dendrons , 2004 .

[24]  J. C. Roberts,et al.  Preliminary biological evaluation of polyamidoamine (PAMAM) Starburst dendrimers. , 1996, Journal of biomedical materials research.

[25]  M. Urdea,et al.  Dendrimer development. , 1993, Science.

[26]  C. Mirkin,et al.  Nanoparticle-Based Bio-Bar Codes for the Ultrasensitive Detection of Proteins , 2003, Science.

[27]  G. Kallos,et al.  Molecular weight determination of a polyamidoamine Starburst polymer by electrospray ionization mass spectrometry , 1991 .

[28]  P. Low,et al.  Indium-111-DTPA-folate as a potential folate-receptor-targeted radiopharmaceutical. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[29]  J. Subbi,et al.  Structural deviations in poly(amidoamine) dendrimers: a MALDI-TOF MS analysis , 2003 .

[30]  Martin W. Brechbiel,et al.  Metal-chelate-dendrimer-antibody constructs for use in radioimmunotherapy and imaging , 1994 .

[31]  Bradford G. Orr,et al.  DNA-Directed Synthesis of Generation 7 and 5 PAMAM Dendrimer Nanoclusters , 2004 .

[32]  G. Wahl,et al.  Derivatization of unprotected polynucleotides. , 1983, Nucleic acids research.

[33]  H Nau,et al.  Determination of folate patterns in mouse plasma, erythrocytes, and embryos by HPLC coupled with a microbiological assay. , 1998, Analytical biochemistry.

[34]  William A. Goddard,et al.  Starburst Dendrimers: Molecular‐Level Control of Size, Shape, Surface Chemistry, Topology, and Flexibility from Atoms to Macroscopic Matter , 1990 .

[35]  P. Low,et al.  Delivery of macromolecules into living cells: a method that exploits folate receptor endocytosis. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[36]  J. Storhoff,et al.  Selective colorimetric detection of polynucleotides based on the distance-dependent optical properties of gold nanoparticles. , 1997, Science.