Hitesh G. Bagaria

A nanocomplex that is both tumor cell-selective and cancer gene-specific for anaplastic large cell lymphoma

BackgroundMany in vitro studies have demonstrated that silencing of cancerous genes by siRNAs is a potential therapeutic approach for blocking tumor growth. However, siRNAs are not cell type-selective, cannot specifically target tumor cells, and therefore have limited in vivo application for siRNA-mediated gene therapy.ResultsIn this study, we tested a functional RNA nanocomplex which exclusively targets and affects human anaplastic large cell lymphoma (ALCL) by taking advantage of the abnormal expression of CD30, a unique surface biomarker, and the anaplastic lymphoma kinase (ALK) gene in lymphoma cells. The nanocomplexes were formulated by incorporating both ALK siRNA and a RNA-based CD30 aptamer probe onto nano-sized polyethyleneimine-citrate carriers. To minimize potential cytotoxicity, the individual components of the nanocomplexes were used at sub-cytotoxic concentrations. Dynamic light scattering showed that formed nanocomplexes were ~140 nm in diameter and remained stable for more than 24 hours in culture medium. Cell binding assays revealed that CD30 aptamer probes selectively targeted nanocomplexes to ALCL cells, and confocal fluorescence microscopy confirmed intracellular delivery of the nanocomplex. Cell transfection analysis showed that nanocomplexes silenced genes in an ALCL cell type-selective fashion. Moreover, exposure of ALCL cells to nanocomplexes carrying both ALK siRNAs and CD30 RNA aptamers specifically silenced ALK gene expression, leading to growth arrest and apoptosis.ConclusionsTaken together, our findings indicate that this functional RNA nanocomplex is both tumor cell type-selective and cancer gene-specific for ALCL cells.

Polyamine–salt aggregate assembly of capsules as responsive drug delivery vehicles

Responsive capsular delivery systems that can partly mimic the complexity of cellular systems hold great promise for the future of medicine. Simple self-assembled systems like liposomes are already in clinical use and others like polymeric micelles are under clinical trials. Unlike these self-assembled systems, the greater flexibility and versatility offered by template-based routes will likely drive the development of sophisticated capsules. The focus of this review is to introduce one such template-based route, which is based on polyamine–salt aggregate or ‘PSA’ assembly. The basic synthesis premise involves the assembly of cationic polymer (like poly-L-lysine) by ionic crosslinking with multivalent anionic salts (like citrate) into metastable templates for cargo encapsulation and shell material deposition. The technique offers several benefits: (i) the synthesis procedure involves simple mixing at ambient conditions, (ii) the capsule size is easy to control in the sub-100 nm to micron range, and (iii) a wide range of formulations is readily available with the use of different polymer, salt, cargo, and shell-forming precursors. In this review, the current state of this technique, the materials chemistry of the capsule assembly, and the demonstrated applications, including photothermal therapy, MRI contrast agent development and protease-responsive NIR imaging, will be discussed.

Formation mechanism and composition distribution of FePt nanoparticles

Self-assembled FePt nanoparticle arrays are candidate structures for ultrahigh density magnetic storage media. One of the factors limiting their application to this technology is particle-to-particle compositional variation. This variation will affect the A1 to L10 transformation as well as the magnetic properties of the nanoparticles. In the present study, an analysis is provided for the formation mechanism of these nanoparticles when synthesized by the superhydride reduction method. Additionally, a comparison is provided of the composition distributions of nanoparticles synthesized by the thermal decomposition of Fe(CO)5 and the reduction of FeCl2 by superhydride. The latter process produced a much narrower composition distribution. A thermodynamic analysis of the mechanism is described in terms of free energy perturbation Monte Carlo simulations.

Molten-droplet synthesis of composite CdSe hollow nanoparticles.

Many colloidal synthesis routes are not scalable to high production rates, especially for nanoparticles of complex shape or composition, due to precursor expense and hazards, low yields, and the large number of processing steps. The present work describes a strategy to synthesize hollow nanoparticles (HNPs) out of metal chalcogenides, based on the slow heating of a low-melting-point metal salt, an elemental chalcogen, and an alkylammonium surfactant in octadecene solvent. The synthesis and characterization of CdSe HNPs with an outer diameter of 15.6 ± 3.5 nm and a shell thickness of 5.4 ± 0.9 nm are specifically detailed here. The HNP synthesis is proposed to proceed with the formation of alkylammonium-stabilized nano-sized droplets of molten cadmium salt, which then come into contact with dissolved selenium species to form a CdSe shell at the droplet surface. In a reaction-diffusion mechanism similar to the nanoscale Kirkendall effect it is speculated that the cadmium migrates outwardly through this shell to react with more selenium, causing the CdSe shell to thicken. The proposed CdSe HNP structure comprises a polycrystalline CdSe shell coated with a thin layer of amorphous selenium. Photovoltaic device characterization indicates that HNPs have improved electron transport characteristics compared to standard CdSe quantum dots, possibly due to this selenium layer. The HNPs are colloidally stable in organic solvents even though carboxylate, phosphine, and amine ligands are absent; stability is attributed to octadecene-selenide species bound to the particle surface. This scalable synthesis method presents opportunities to generate hollow nanoparticles with increased structural and compositional variety.

Templating CdSe tetrapods at the air/water interface with POPC lipids.

Surfactants have been widely used as templating agents to pattern the orientation of nanoparticles of various conformations. Here we report the use of a lipid, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), as a template to order CdSe tetrapods (TPs) at the air/water interface using a Langmuir-Blodgett trough. The surface pressure versus area isotherms for CdSe TPs and CdSe TPs/POPC are examined and monitored by Brewster angle microscopy (BAM). The transferred thin films are further characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM). Initially disc-like structures containing randomly oriented TPs form during solvent evaporation. Upon decreasing surface area, these discs merge into larger continental structures. In a mixed CdSe TPs/POPC system, these discs organize into wire-like networks upon compression. We detail how lipid molecules can be used to direct the two-dimensional assembly of TPs.

Performance of CdSe tetrapods-gold as nanostructure electrochemical materials in photovoltaic cells

Nanoscale rectennae (rectifying antennae) have been fabricated by combining rectifying organic self-assembled monolayers (SAM) with plasmonic materials because of their surface plasmon resonance (SPR) properties of capturing light. Gold antenna arrays are assembled by coating on CdSe tetrapod templates; the rectifying barrier is formed by self-assembled monolayer (SAM) of gold and electrolyte which contains alkylthiolate. Photocurrent measurements showed that electric currents can be induced at different wavelengths within visible range that strongly depend on the aspect ratio of the tetrapod. Adding gold layer can increase the generated photocurrents due to the rectification. Multiple mechanisms among the semiconductors, metals and electrolytes in response of photocurrent are indicated and analyzed.