Zeid A. Nima

Circulating tumor cell identification by functionalized silver-gold nanorods with multicolor, super-enhanced SERS and photothermal resonances

Nanotechnology has been extensively explored for cancer diagnostics. However, the specificity of current methods to identify simultaneously several cancer biomarkers is limited due to color overlapping of bio-conjugated nanoparticles. Here, we present a technique to increase both the molecular and spectral specificity of cancer diagnosis by using tunable silver-gold nanorods with narrow surface-enhanced Raman scattering (SERS) and high photothermal contrast. The silver-gold nanorods were functionalized with four Raman-active molecules and four antibodies specific to breast cancer markers and with leukocyte-specific CD45 marker. More than two orders of magnitude of SERS signal enhancement was observed from these hybrid nanosystems compared to conventional gold nanorods. Using an antibody rainbow cocktail, we demonstrated highly specific detection of single breast cancer cells in unprocessed human blood. By integrating multiplex targeting, multicolor coding, and multimodal detection, our approach has the potential to improve multispectral imaging of individual tumor cells in complex biological environments.

Impact of Carbon Nanotube Exposure to Seeds of Valuable Crops

Multiwalled carbon nanotubes (MWCNTs) affected seed germination, growth, and the development of three important crops (barley, soybean, corn). Early seed germination and activation of growth in exposed seedlings was observed when MWCNTs were added to sterile agar medium. Similarly, seed germination was activated for all tested crop species when MWCNTs were deposited on seed surfaces. The ability of MWCNTs to penetrate the seed coats of corn, barley, and soybean was proven by detection of nanotube agglomerates inside MWCNT-exposed seeds using Raman spectroscopy and transmission electron microscopy (TEM). Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that the expression of genes encoding several types of water channel proteins was increased in soybean, corn, and barley seeds coated with MWCNTs compared with uncoated control seeds. Our results indicate that the positive effect of MWCNTs on the germination and growth of seedlings is reproducible between crop species and can be observed for different methods of delivering carbon nanotubes. Such studies could prove the significant potential of carbon nanotubes as regulators of germination and plant growth.

Applications of surface-enhanced Raman scattering in advanced bio-medical technologies and diagnostics.

Abstract In this review of the literature on surface-enhanced Raman scattering (SERS), we describe recent developments of this technique in the medical field. SERS has developed rapidly in the last few years as a result of the fascinating advancements in instrumentation and the ability to interpret complex Raman data using high-processional, computer-aided programs. This technique, has many advantages over ordinary spectroscopic analytical techniques – such as extremely high sensitivity, molecular selectivity, intense signal and great precision – that can be leveraged to address complex medical diagnostics problems. This review focuses on the SERS-active substrate, as well as major advances in cancer and bacteria detection and imaging. Finally, we present a perspective on anticipated future advancements in SERS techniques to address some of the most critical challenges in the areas of diagnostics, detection, and sensing.

Single-walled carbon nanotube and graphene nanodelivery of gambogic acid increases its cytotoxicity in breast and pancreatic cancer cells.

Graphene and single‐walled carbon nanotubes were used to deliver the natural low‐toxicity drug gambogic acid (GA) to breast and pancreatic cancer cells in vitro, and the effectiveness of this complex in suppressing cellular integrity was assessed. Cytotoxicity was assessed by measuring lactate dehydrogenase release, mitochondria dehydrogenase activity, mitochondrial membrane depolarization, DNA fragmentation, intracellular lipid content, and membrane permeability/caspase activity. The nanomaterials showed no toxicity at the concentrations used, and the antiproliferative effects of GA were significantly enhanced by nanodelivery. The results suggest that these complexes inhibit human breast and pancreatic cancer cells grown in vitro. This analysis represents a first step toward assessing their effectiveness in more complex, targeted, nanodelivery systems. Copyright

Raman spectroscopy as a detection and analysis tool for in vitro specific targeting of pancreatic cancer cells by EGF‐conjugated, single‐walled carbon nanotubes

Single‐walled carbon nanotubes (SWCNTs) were covalently linked to epidermal growth factor (EGF) proteins through an esterification process that was found to be responsible for the docking of SWCNTs on the human pancreatic cancer cells (PANC‐1) surface, thus providing a mechanism for the enhanced delivery and internalization of the nanotubes. Micro Raman spectroscopy and enzyme‐linked immunosorbent assay were used to evaluate the delivery process and kinetics of the SWCNTs. In vitro studies indicated that the delivery kinetics of SWCNT–EGF conjugates, at a concentration of 85 µg ml−1, to the PANC‐1 cell surfaces was significant in the first 30 min of incubation, but reached a plateau with time in accordance with the establishment of equilibrium between the association and the dissociation of EGF with the cell receptors. SWCNT–EGF conjugates could act as strong thermal ablation agents and could induce higher percentages of cellular death compared with the nontargeted SWCNTs alone. Copyright

Single-walled carbon nanotubes as specific targeting and Raman spectroscopic agents for detection and discrimination of single human breast cancer cells

Abstract. Raman active nano-complex agents based on single-walled carbon nanotubes (SWCNTs) are prepared and used for the swift and specific detection of breast cancer cells. SWCNTs are functionalized to bond covalently with the anti-epithelial cell adhesion molecule (anti-EpCAM) antibody, which is specific to the highly expressed EpCAM antigen on the surface of breast cancer cells (MCF-7), but not on normal cells. The Raman nano-complexes demonstrate excellent ability to detect in vitro single breast cancer cells (MCF-7) and discriminate between them and normal fibroblast cells during the first 30 min of the targeting process. Raman linearity scanning is collected from a monolayer cell mixture, including both cancer cells and normal cells incubated with anti-EpCAM-SWCNTs, using a 633-nm laser excitation. The results shows that the Raman signal collected from targeted MCF-7 cells is extremely high, whereas there is little signal from the normal cells.

Plasmonically active nanorods for delivery of bio-active agents and high-sensitivity SERS detection in planta

Multifunctional, plasmonically-active nanorods based on gold cores and silver shells (AuNR/Ag), after exposure to tomato plants, were found to be taken up in rather short times, being detected by SERS in both roots and stems, while exhibiting lack of phytotoxicity in the concentrations used during this study. Additionally, we report that AuNR/Ag have the ability to deliver auxin growth regulator 2,4-D, which resulted in a significant impact on the regulation of tobacco cell culture growth. The unique morphology of these nanorods allowed their sensitive SERS detection, resulting in a technological approach that combines both high-sensitivity detection and delivery of biologically active molecules to plant tissues or cells. Here, we demonstrate that the multiplex combination of plasmonically active agents, laser spectroscopy, and plant biology could represent a new direction in bio-nano-engineering that integrates the use of spectroscopically-active systems for delivery of active compounds and ultra-sensitive detection in plants.

Spaser as a biological probe.

Understanding cell biology greatly benefits from the development of advanced diagnostic probes. Here we introduce a 22-nm spaser (plasmonic nanolaser) with the ability to serve as a super-bright, water-soluble, biocompatible probe capable of generating stimulated emission directly inside living cells and animal tissues. We have demonstrated a lasing regime associated with the formation of a dynamic vapour nanobubble around the spaser that leads to giant spasing with emission intensity and spectral width >100 times brighter and 30-fold narrower, respectively, than for quantum dots. The absorption losses in the spaser enhance its multifunctionality, allowing for nanobubble-amplified photothermal and photoacoustic imaging and therapy. Furthermore, the silica spaser surface has been covalently functionalized with folic acid for molecular targeting of cancer cells. All these properties make a nanobubble spaser a promising multimodal, super-contrast, ultrafast cellular probe with a single-pulse nanosecond excitation for a variety of in vitro and in vivo biomedical applications.

Polydopamine-Coated Manganese Complex/Graphene Nanocomposite for Enhanced Electrocatalytic Activity Towards Oxygen Reduction.

Platinum electrodes are commonly used electrocatalysts for oxygen reduction reactions (ORR) in fuel cells. However, this material is not economical due to its high cost and scarcity. We prepared an Mn(III) catalyst supported on graphene and further coated with polydopamine, resulting in superior ORR activity compared to the uncoated PDA structures. During ORR, a peak potential at 0.433 V was recorded, which is a significant shift compared to the uncoated material’s −0.303 V (both versus SHE). All the materials reduced oxygen in a wide pH range via a four-electron pathway. Rotating disk electrode and rotating ring disk electrode studies of the polydopamine-coated material revealed ORR occurring via 4.14 and 4.00 electrons, respectively. A rate constant of 6.33 × 106 mol−1s−1 was observed for the polydopamine-coated material–over 4.5 times greater than the uncoated nanocomposite and superior to those reported for similar carbon-supported metal catalysts. Simply integrating an inexpensive bioinspired polymer coating onto the Mn-graphene nanocomposite increased ORR performance significantly, with a peak potential shift of over +730 mV. This indicates that the material can reduce oxygen at a higher rate but with lower energy usage, revealing its excellent potential as an ORR electrocatalyst in fuel cells.

Bone-tissue engineering: complex tunable structural and biological responses to injury, drug delivery, and cell-based therapies

Abstract Bone loss and failure of proper bone healing continues to be a significant medical condition in need of solutions that can be implemented successfully both in human and veterinary medicine. This is particularly true when large segmental defects are present, the bone has failed to return to normal form or function, or the healing process is extremely prolonged. Given the inherent complexity of bone tissue – its unique structural, mechanical, and compositional properties, as well as its ability to support various cells – it is difficult to find ideal candidate materials that could be used as the foundation for tissue regeneration from technological platforms. Recently, important developments have been made in the implementation of complex structures built both at the macro- and the nano-level that have been shown to positively impact bone formation and to have the ability to deliver active biological molecules (drugs, growth factors, proteins, cells) for controlled tissue regeneration and the prevention of infection. These materials are diverse, ranging from polymers to ceramics and various composites. This review presents developments in this area with a focus on the role of scaffold structure and chemistry on the biologic processes that influence bone physiology and regeneration.