Lars T. Piehler
University of Michigan
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Featured researches published by Lars T. Piehler.
Pharmaceutical Research | 2002
Antonio Quintana; Ewa Raczka; Lars T. Piehler; Inhan Lee; Andrzej Myc; Istvan J. Majoros; Anil K. Patri; Thommey P. Thomas; James J. Mulé; R James BakerJr.
AbstractPurpose. We sought to develop nanoscale drug delivery materials that would allow targeted intracellular delivery while having an imaging capability for tracking uptake of the material. A complex nanodevice was designed and synthesized that targets tumor cells through the folate receptor. Methods. The device is based on an ethylenediamine core polyamidoamine dendrimer of generation 5. Folic acid, fluorescein, and methotrexate were covalently attached to the surface to provide targeting, imaging, and intracellular drug delivery capabilities. Molecular modeling determined the optimal dendrimer surface modification for the function of the device and suggested a surface modification that improved targeting. Results. Three nanodevices were synthesized. Experimental targeting data in KB cells confirmed the modeling predictions of specific and highly selective binding. Targeted delivery improved the cytotoxic response of the cells to methotrexate 100-fold over free drug. Conclusions. These results demonstrate the ability to design and produce polymer-based nanodevices for the intracellular targeting of drugs, imaging agents, and other materials.
The Journal of Infectious Diseases | 2002
Jeffrey J. Landers; Zhengyi Cao; Inhan Lee; Lars T. Piehler; Piotr P. Myc; Andrzej Myc; Tarek Hamouda; Andrzej T. Galecki; James R. Baker
Influenza A viral infection begins by hemagglutinin glycoproteins on the viral envelope binding to cell membrane sialic acid (SA). Free SA monomers cannot block hemagglutinin adhesion in vivo because of toxicity. Polyvalent, generation 4 (G4) SA-conjugated polyamidoamine (PAMAM) dendrimer (G4-SA) was evaluated as a means of preventing adhesion of 3 influenza A subtypes (H1N1, H2N2, and H3N2). In hemagglutination-inhibition assays, G4-SA was found to inhibit all H3N2 and 3 of 5 H1N1 influenza subtype strains at concentrations 32-170 times lower than those of SA monomers. In contrast, G4-SA had no ability to inhibit hemagglutination with H2N2 subtypes or 2 of 5 H1N1 subtype strains. In vivo experiments showed that G4-SA completely prevented infection by a H3N2 subtype in a murine influenza pneumonitis model but was not effective in preventing pneumonitis caused by an H2N2 subtype. Polyvalent binding inhibitors have potential as antiviral therapeutics, but issues related to strain specificity must be resolved.
Biomedical Microdevices | 2001
James R. Baker; Antonio Quintana; Lars T. Piehler; Mark Banazak-Holl; Donald A. Tomalia; Ewa Raczka
Nanotechnology provides the sized materials that can be synthesized and function in the same general size range and Biologic structures. We have attempted to develop forms of anticancer therapeutics based on nanomaterials. Our project seeks to develop dendritic polymer nanodevices that serve as a means for the detection of cancer cells, the identification of cancer signatures, and the targeted delivery of anti-cancer therapeutics (cis-platin, methotrexate, and taxol) and contrast agents to tumor cells. Initial studies documented the synthesis and function of a targeting module, several drug delivery components, and two imaging/contrast agents. Analytical techniques have been developed and used to confirm the structure of the device. Progress has been made on the specifically triggered release of the therapeutic agent within a tumor using high-energy lasers. The work to date has demonstrated the feasibility of the nano-device concept in actual cancer cells in vitro.
Proceedings of the National Academy of Sciences of the United States of America | 2002
Donald A. Tomalia; Lars T. Piehler; H. Dupont Durst; Douglas R. Swanson
Poly(amidoamine) (PAMAM) dendrimer shell reagents possessing either nucleophilic (i.e., primary amines) or electrophilic (i.e., carboxymethyl esters) functional groups have been covalently assembled around appropriate electrophilic or nucleophilic dendrimer core reagents to produce partial shell filled/core-shell tecto(dendrimers). Partial shell-filled products with saturation levels ranging from 28% to 66% were obtained. These metastable, remarkably monodispersed assemblies possess functionally differentiated nano-cusps and clefts that exhibit “autoreactive” behavior. Pacification of these autoreactive products with appropriate alkanolamine reagents produced robust, nonreactive, “hydroxy-amine-differentiated” surfaces that exhibit very active self-assembly properties. Based on the monodispersity, dimensional scaling, and electrophoretic similarities of PAMAM dendrimers to globular proteins, these assemblies may be viewed as crude biomimetics of classical core shell-type protein aggregates. These dimensionally larger, but analogous PAMAM core-shell tecto(dendrimer) architectures extend and complete a similar pattern of autoreactivity and pacification that was observed earlier for traditional mono PAMAM dendrimer core-shell modules possessing unsaturated shell levels.
Archive | 1995
Donald A. Tomalia; James R. Baker; Roberta C. Cheng; Anna U. Bielinska; Michael J. Fazio; David M. Hedstrand; Jennifer A. Johnson; Donald A. Kaplan; Scott L. Klakamp; William J. Kruper; Jolanta F. Kukowska-Latallo; Bartley D. Maxon; Lars T. Piehler; Ian A. Tomlinson; Larry R. Wilson; Rui Yin
Langmuir | 2000
J. Li; Lars T. Piehler; Dujie Qin; James R. Baker; Donald A. Tomalia; D. J. Meier
Bioconjugate Chemistry | 1999
Jon D. Reuter; Andrzej Myc; Michael M. Hayes; Zhonghong Gan; Rene Roy; Dujie Qin; Rui Yin; Lars T. Piehler; Roseita Esfand; Donald A. Tomalia; James R. Baker
Langmuir | 1999
J. Li; Douglas R. Swanson; Dujie Qin; Lars T. Piehler; Donald A. Tomalia; D. J. Meier
Archive | 1995
James R. Baker; Anna U. Bielinska; Roberta C. Cheng; Michael J. Fazio; David M. Hedstrand; Jennifer A. Johnson; Donald A. Kaplan; Scott L. Klakamp; Jr William J. Kruper; Jolanta F. Kukowska-Latallo; Bartley D. Maxon; Lars T. Piehler; Donald A. Tomalia; Ian A. Tomlinson; Larry R. Wilson; Rui Yin
Archive | 1995
James R. Baker; Anna U. Bielinska; Roberta C. Cheng; Michael J. Fazio; David M. Hedstrand; Jennifer A. Johnson; Donald A. Kaplan; Scott L. Klakamp; William J. Kruper; Jolanta F. Kukowska-Latallo; Bartley D. Maxon; Lars T. Piehler; Donald A. Tomalia; Ian A. Tomlinson; Larry R. Wilson; Rui Yin