AVS2011 Session NS-ThA: Biological Nanomaterials

We have recently demonstrated that we can stabilize magnetite nanoparticles which fulfil these stability criteria using self-assembling dispersants with nitrocatechol anchors (1-2). This allows us free control over the dispersant type by simple co-adsorption of dispersants to as-synthesized core Fe₃O₄ particles. Combined with independent control over the Fe₃O₄ core size in the range 3-15 nm a versatile toolbox for assembly of various smart materials and for biomedical applications has been created.

This presentation is focussed on recent results demonstrating and characterizing assembly of such nanoparticles into membranes of stealth liposomes (3). We show that there are strict requirements for the size of particles that can be assembled into lipid bilayer membranes and that a requirement for efficient assembly and actuation as well as liposome stability is to ensure stability of the hydrophobic shell surrounding the nanoparticle within the membrane. Encapsulated molecules were released multiple times by application of short bursts of alternating magnetic fields through a localized phase change in the membrane without heating of the surrounding aqueous environment. This allowed control of both timing and dose of release. The highest efficiency of release and encapsulation was obtained for irreversibly stabilized superparamagnetic iron oxide nanoparticles with diameters <6 nm inserted into the lipid membrane.

1. E. Amstad et al., Nano Lett, 9:4042 (2009)

2. E. Amstad et al., J Phys Chem C 115:683-691 (2011)

3. E. Amstad et al., Nano Lett, 11:1664-1670 (2011)

Carbon nanotube-biomolecule hybrids have emerged as one of the most promising materials for biological and biomedical applications, such as biosensors, drug delivery, and imaging. Recently, Carbon nanotubes (CNTs) have shown the ability to protect bound DNA cargos from enzymatic cleavage both during and after delivery into cells. This ability may result from the interaction between CNTs and DNA, which makes DNA unrecognizable to enzyme binding pockets. Therefore, it is important to study the interaction between CNTs and DNA. In this work, we have developed a nanoscale optoelectronic probing system by combining highly-sensitive CNT transistors with advanced dual-trap optical tweezers to investigate the interaction between CNTs and DNA at the single-molecule level. We tightly bonded both ends of a DNA molecule with microbeads, which could be held and manipulated by optical tweezers. When the DNA molecule was moved close to a suspended CNT transistor, the negative charge from the DNA molecule would change the local electrostatic environment around the CNT. Through scanning photocurrent measurements, the electrical coupling between individual DNA molecules and CNTs could be investigated.

The reported positive margin rate from wire localized excisions of breast cancers is approximately 20-50%; however, using radioactive seeds and a radiation detector the excision rate is halved because the surgeon can constantly reorient the dissection to place the seed in the center of the specimen. Unfortunately, radioactive seed localization has several safety challenges, only single foci can be localized, and incisions are required to implant the seeds, so it is rarely employed. As a safe alternative, gas-filled hollow boron-doped silica particles have been developed, which can be used for ultrasound-guided surgery for multiple focii. The function of the boron doping is to increase the mechanical strength of the silica shell. The particles are synthesized through a sol-gel method on a polystyrene template, and subsequently calcined to create hollow, rigid microspheres. The boron doped silica shell is derived from tetramethoxy orthosilicate (TMOS) and trimethyl borate (TMB), which forms a rigid, mesoporous shell upon calcination. The microshells are filled with perfluoropentane vapor. The perfluorocarbon vapor is contained within the porous shell due to its extremely low solubility in water. In addition, the high surface tension of water may serve to seal the fluorous phase within the pores of the shell wall as water enters the outer surface of the porous shell by capillary action. Considerable testing of particle functionality, signal persistence and acoustical properties have been performed in various phantoms including ultrasound gel, chicken breast, and excised human mastectomy tissue. Furthermore, preliminary particle injection longevity studies have been performed in a rabbit animal model. In vitro studies have shown that continuous particle imaging time is up to approximately 45 minutes. In vivo studies have shown consistent signal presence even 48 hours post injection in rabbits with an injection volume of 50 μl carrying only 100 μg of particles. As a result these particles may provide a significant improvement over current methods in terms of patient comfort in having a small injection 1-2 days prior to surgery. On going studies are currently aimed at improving the understanding of the mechanism by which these microspheres are capable of producing such robust signal under color doppler ultrasound.