George W. Pratt

Treating metastatic cancer with nanotechnology

Metastasis accounts for the vast majority of cancer deaths. The unique challenges for treating metastases include their small size, high multiplicity and dispersion to diverse organ environments. Nanoparticles have many potential benefits for diagnosing and treating metastatic cancer, including the ability to transport complex molecular cargoes to the major sites of metastasis, such as the lungs, liver and lymph nodes, as well as targeting to specific cell populations within these organs. This Review highlights the research, opportunities and challenges for integrating engineering sciences with cancer biology and medicine to develop nanotechnology-based tools for treating metastatic disease.

Peptide Secondary Structure Modulates Single-Walled Carbon Nanotube Fluorescence as a Chaperone Sensor for Nitroaromatics

A class of peptides from the bombolitin family, not previously identified for nitroaromatic recognition, allows near-infrared fluorescent single-walled carbon nanotubes to transduce specific changes in their conformation. In response to the binding of specific nitroaromatic species, such peptide–nanotube complexes form a virtual “chaperone sensor,” which reports modulation of the peptide secondary structure via changes in single-walled carbon nanotubes, near-infrared photoluminescence. A split-channel microscope constructed to image quantized spectral wavelength shifts in real time, in response to nitroaromatic adsorption, results in the first single-nanotube imaging of solvatochromic events. The described indirect detection mechanism, as well as an additional exciton quenching-based optical nitroaromatic detection method, illustrate that functionalization of the carbon nanotube surface can result in completely unique sites for recognition, resolvable at the single-molecule level.

Modular ‘Click-in-Emulsion’ Bone-Targeted Nanogels

A new class of nanogel demonstrates modular biodistribution and affinity for bone. Nanogels, ∼70 nm in diameter and synthesized via an astoichiometric click-chemistry in-emulsion method, controllably display residual, free clickable functional groups. Functionalization with a bisphosphonate ligand results in significant binding to bone on the inner walls of marrow cavities, liver avoidance, and anti-osteoporotic effects.

Ultrasonic measurement of immobilization-induced osteopenia: An experimental study in sheep

SummaryAn animal model was used to examine the use of noninvasive transmission ultrasound to measure changes in bone mass which occur following disuse. Unilateral achilles tenectomy was performed on the left leg of eight adult sheep. Following a 12-week period of nonweight bearing, presacrifice transmission ultrasound measurements were taken across the calcanei of the intact and the experimental limbs and compared with those values taken postoperatively. Following specimen harvest, cross-sectional areas of the bones were quantified by microradiography and stereology, and compared with thein vivo ultrasound measurements. There was an average of 8.6% less total bone area, and 18.0% less trabecular volume fraction in the experimental nonweight-bearing limbs as compared with control intact calcanei. The difference in bone mass was associated with a 9.0% decrease in the velocity of sound from the postoperative to the presacrifice ultrasound measurements taken from the experimental calcanei, and a 2.3% increase in the control calcanei. The velocity of sound was found by the Studentst test to be a highly reliable discriminator between the experimental and control limbs.

An evaluation of total hip replacement cementing technique using sonic resonance

The feasibility of assessing the quality of the bond achieved by cement fixation of implants by their sonic characteristics was examined by theoretical and experimental models. Mechanical excitation of implants in the audio sonic range in vitro produced experimental results that were in close agreement with computer predicted values. The sonic technique was utilized to evaluate certain aspects of current surgical technique using in vitro models. By sonic criteria, steady state polymerization of surgical simplex cement occurs approximately eleven minutes after hand held cement has cured. The value of meticulous preparation of bone surfaces prior to cement introduction is confirmed. Differences in the quality of bond obtained by variations in cement technique, or recementing to old cement, can be distinguished by this method. These results suggest that sonic assessment may provide a more sensitive measure of the quality of bond achieved than does roentgen examination. In clinical use, both intra-operatively and post-operatively, application of this technique may yield an immediate assessment of the quality of cement fixation.

Optical modulation of second‐harmonic generation in tellurium

Modulation of second‐harmonic generation in tellurium by a 5.3‐μm signal beam is analyzed. The signal beam in combination with the other beams in the process (10.6 μm doubling to 5.3 μm) generates free carriers by two‐photon absorption. The resultant free carriers decrease the refractive index and increase the loss tangent of the material, thereby interfering with the second‐harmonic generation process. The process is examined here both theoretically and experimentally. It is shown that the modulation efficiency can be as great as 100%. The prospect of achieving a usable power gain in a simple crystal of tellurium is shown to be unlikely, but the analysis points to promising alternatives.