Enhancement of laser-induced optical breakdown using metal/dendrimer nanocomposites

We demonstrate that dendrimer nanocomposites (DNC) can be used to remarkably change the laser-induced optical breakdown (LIOB) threshold of a material, owing to a large enhancement of the local electric field. We have implemented LIOB using femtosecond laser pulses in a gold/dendrimer hybrid nanocomposite as a model system. Third-harmonic generation measurements have been employed as a sensitive way for monitoring the LIOB in situ and in real time. The observed statistical behavior of the breakdown process is attributed to a laser-driven aggregation of individual DNC particles. The breakdown threshold value of the DNC has been found to be up to two orders of magnitude lower than that of pure dendrimers or normal tissues. © 2002 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69960/2/APPLAB-80-10-1713-1.pd

MN2006-17025 BIODISTRIBUTION OF DENDRIMER NANOCOMPOSITES FOR NANO-RADIATION THERAPY OF CANCER

ABSTRACT Multifunctional nanocomposites have an enormous scientific and practical future in medicine, especially in biomedical imaging and targeted delivery. Multifunctional composite nanodevices (CND) possess chemical and physical properties of all components, while interactions with the environment of the nanoparticle are dominated by the contact surface of the host molecule. Thus, if the surface is dominated by the organic component of a nanosized organic-inorganic composite particle, an inorganic particle property can be manipulated in a biologic environment as if it belonged to an organic macromolecule. Composition, charge, and size of are critical in determining nanoparticle trafficking and uptake by organs, and therefore this knowledge is crucial for the development of cancer imaging and therapies. Specific biokinetics and biodistribution then can be influenced by correctly selecting size, and modifying surface characteristics, such as covalently attaching various targeting moieties to the surface forming biohybrids, regulating the surface charge, etc. Dendrimer nanocomposites are recently developed nearly monodisperse hybrid nanoparticles composed of macromolecular hosts and very small, uniformly dispersed inorganic guest domains combining desirable properties of the components. The surface groups control the interaction of these nanodevices with the biological environment. As a result of various synthetic options, the interior and/or the exterior of the host can be cationic, anionic, or non-ionic, depending on their termini and interior functionalities and the pH, and may involve multiple targeting moieties. We have synthesized gold/dendrimer nanocomposites to carry payload radiation and/or diagnostic moiety to specific targets. We examined the biodistribution of the templates and the corresponding gold/dendrimer nanocomposites. We employed the same dendrimer template and systematically varied the size, the surface charge and the composition. Biodistribution of {Au} gold/dendrimer nanodevices of various size (5, 12 and 22 nm) and surface charge (positive, negative) was investigated in mice models (B16 melanoma and DU145 human prostate cancer). Isotope neutron activation analysis (INAA) was used to measure the presence of Au(0) in the tissue sample. All {Au} gold/dendrimer-nanocomposites were assayed for their quantitative short-term (1hr), intermediate (1 day) and long-term (4 days) biodistribution throughout organs for clinical toxicity. Delivery of radiation dose was achieved by radioactive { 198 Au} composites in a mice model. We have shown that modulating surface charge and composition will greatly change the biodistribution characteristics of the nanodevices. Rigorous testing of the principles that govern nanoparticle interactions with the complex environment of biological systems will be critical for an understanding of how these nanodevices will behave in vivo

Self Assembly and Optical Properties of Dendrimer Nanocomposite Multilayers

Ultrathin multilayers are important for electrical and optical devices, as well as for immunoassays, artificial organs, and for controlling surface properties. The construction of ultrathin multilayer films by electrostatic layer-by-layer deposition proved to be a popular and successful method to create films with a range of electrical, optical, and biological properties. Dendrimer nanocomposites (DNCs) form highly uniform hybrid (inorganic–organic) nanoparticles with controlled composition and architecture. In this work, the fabrication, characterization, and optical properties of ultrathin dendrimer/poly(styrene sulfonate) (PSS) and silver–DNC/PSS nanocomposite multilayers using layer-by-layer (LbL) electrostatic assembly techniques are described. UV-vis spectra of the multilayers were found to be a combination of electronic transitions of the surface plasmon peaks, and the regular frequency modulations attributable to the multilayered film structure. The modulations appeared as the consequence of the highly regular and non-intermixed multilayer growth as a function of the resulting structure. A simple model to explain the experimental data is presented. Use of DNCs in multilayers results in abrupt, flat, and uniform interfaces.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56176/1/1032_ftp.pd

Ultrafast time-resolved photoluminescence from novel metal–dendrimer nanocomposites

We report the first results of ultra-fast enhanced light emission from gold– and silver–dendrimer nanocomposites. There is a fast (70 fs) fluorescence decay component associated with the metal nanocomposites. Anisotropy measurements show that this fast component is depolarized. The enhanced emission is suggestively due to local field enhancement in the elongated metal–dendrimer nanoparticles. © 2001 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71043/2/JCPSA6-114-5-1962-1.pd

Synthesis, characterization, and manipulation of dendrimer-stabilized iron sulfide nanoparticles

FeS nanoparticles (NPs) were synthesized using ethylenediamine core poly(amidoamine) (PAMAM) dendrimers of generation 4 terminated with amino (G4·NH2), hydroxyl (G4·NGlyOH), and carboxyl (G4·SAH) groups, respectively, as stabilizers. These dendrimer-stabilized FeS NPs (FeS DSNPs) were characterized by ultraviolet–visible (UV–vis) spectrometry, zeta-potential measurements, and transmission electron microscopy (TEM). Deposition of FeS NPs onto mesoporous silica gel microparticles was attempted using two approaches: (A) direct coating of {FeS–G4·NH2} DSNPs onto silica particles; and (B) using G4·NH2-coated silica particles to incorporate Fe2+ ions for the subsequent formation of FeS NPs. Scanning electron microscopy (SEM) studies show that approach (B) was much more efficient in the incorporation of FeS NPs than approach (A). Such preparation and manipulation of FeS DSNPs provides a unique strategy for fabricating various reactive nanoplatforms for environmental remediation applications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49224/2/nano6_18_005.pd

Characterization of crystalline dendrimer-stabilized gold nanoparticles

Monodispersed, highly crystalline dendrimer-stabilized gold nanoparticles (Au DSNPs) were synthesized via hydrazine reduction chemistry and stabilized using primary amine-terminated poly(amidoamine) (PAMAM) dendrimers of different generations (generations 2–6) with the same molar ratios of dendrimer terminal nitrogen ligands/gold atoms. The sizes of the synthesized Au DSNPs decrease with the increase of the number of dendrimer generations. These Au DSNPs are fluorescent and display strong blue emission intensity at 458 nm. Polyacrylamide gel electrophoresis (PAGE) analysis indicates that all Au DSNPs are stable and both metal NPs and dendrimer stabilizers do not separate from each other during the electrophoresis process. The synthesized inorganic/organic hybrid Au DSNPs provide new nanoplatforms that will be further modified with various biological ligands for the application of biosensing and targeted cancer therapeutics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49227/2/nano6_4_038.pd

Formation of Silver and Gold Dendrimer Nanocomposites

Structural types of dendrimer nanocomposites have been studied and the respective formation mechanisms have been described, with illustration of nanocomposites formed from poly(amidoamine) PAMAM dendrimers and zerovalent metals, such as gold and silver. Structure of {(Au(0)) n− PAMAM} and {(Ag(0)) n− PAMAM} gold and silver dendrimer nanocomposites was found to be the function of the dendrimer structure and surface groups as well as the formation mechanism and the chemistry involved. Three different types of single nanocomposite architectures have been identified, such as internal (‘I’), external (‘E’) and mixed (‘M’) type nanocomposites. Both the organic and inorganic phase could form nanosized pseudo-continuous phases while the other components are dispersed at the molecular or atomic level either in the interior or on the surface of the template/container. Single units of these nanocomposites may be used as building blocks in the synthesis of nanostructured materials.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43294/1/11051_2004_Article_211595.pd

Acoustic detection of microbubble formation induced by enhanced optical breakdown of silver/dendrimer nanocomposites

We utilize a real-time acoustic technique, based on pulse-echo measurements to detect formation of microbubbles in an aqueous solution of a silver/dendrimer nanocomposite (DNC). Wave-field plots of successive recordings illustrate the generation and behavior of bubbles created by the optical breakdown process. A significant threshold reduction is achieved with DNC particles compared to its host dendrimer, enabling a diverse field of low-threshold breakdown applications. © 2003 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70570/2/APPLAB-82-6-994-1.pd

3 H Dendrimer Nanoparticle Organ/Tumor Distribution

Purpose. To determine the in vivo biodistribution for differently charged poly(amidoamine) (PAMAM) dendrimers in B16 melanoma and DU145 human prostate cancer mouse tumor model systems.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41504/1/11095_2004_Article_482250.pd

Membrane fluidity matters: Hyperthermia from the aspects of lipids and membranes

Hyperthermia is a promising treatment modality for cancer in combination both with radio- and chemotherapy. In spite of its great therapeutic potential, the underlying molecular mechanisms still remain to be clarified. Due to lipid imbalances and 'membrane defects' most of the tumour cells possess elevated membrane fluidity. However, further increasing membrane fluidity to sensitise to chemo-or radiotherapy could have some other effects. In fact, hyperfluidisation of cell membrane induced by membrane fluidiser initiates a stress response as the heat shock protein response, which may modulate positively or negatively apoptotic cell death. Overviewing some recent findings based on a technology allowing direct imaging of lipid rafts in live cells and lipidomics, novel aspects of the intimate relationship between the 'membrane stress' of tumour cells and the cellular heat shock response will be highlighted. Our findings lend support to both the importance of membrane remodelling and the release of lipid signals initiating stress protein response, which can operate in tandem to control the extent of the ultimate cellular thermosensitivity. Overall, we suggest that the fluidity variable of membranes should be used as an independent factor for predicting the efficacy of combinational cancer therapies