John C. Bischof

Abstract: Cryosurgery, or tissue destruction by controlled freezing, has been investigated as a possible alternative to surgical intervention in the treatment of many diseases. This technique, which is under the larger category of thermal therapy, has its origins in the 1800s when advanced carcinomas of the breast and uterine cervix were treated with iced saline solutions. Since those early times, this technique has been used routinely to treat malignancies on the surface of the body (ie, dermatologic tumors) and has gained some acceptance as a clinical tool for the management of internal malignancies, including carcinoma of the prostate and kidney. The main advantages of the technique are the potential for less invasiveness and lower morbidity compared with surgical excision. The study of the destructive process of freezing is the focus of this article and is divided into 2 main areas: (1) understanding the mechanism by which freezing destroys tissue, and (2) understanding the thermal history that causes tissue destruction. The term "thermal history," as used in this article, will mean the time-temperature history experienced by the tissue during a thermal insult.

Abstract: A compelling vision in nanomedicine is the use of self directed nanoparticles that can accumulate in areas of disease to perform designed functions, such as molecular delivery or destruction, endosomal release of genes or siRNA, and selective cell or tumor destruction with nano to macroscale spatiotemporal control and precision. These functions are increasingly achieved by gold nanoparticles (GNPs, such as sphere, shell or rod) that can be activated with a laser “switch”. A defining aspect of this “switch” is GNP absorption of laser light and the ensuing heat generation and temperature change that can be confined or propagated through multiple scales from the nanoparticle surface up through bulk biological cells and tissues. In this critical review, we discuss the fundamental mechanisms of laser GNP heat generation, the measurement and modelling of the ensuing thermal response, and a number of the evolving biological applications dependent on this new technology (181 references).

Abstract: Previous intracytoplasmic sperm injection (ICSI) studies have indicated significant variation in ICSI success rates among different species. In mouse ICSI, the zona pellucida (ZP) undergoes a "hardening" process at fertilization in order to prevent subsequent sperm from penetrating. There have been few studies investigating changes in the mechanical properties of mouse ZP post fertilization. To characterize mouse ZP mechanical properties and quantitate the mechanical property differences of the ZP before and after fertilization, a microelectromechanical systems-based multiaxis cellular force sensor has been developed. A microrobotic cell manipulation system employing the multiaxis cellular force sensor is used to conduct mouse ZP force sensing, establishing a quantitative relationship between applied forces and biomembrane structural deformations on both mouse oocytes and embryos. An analytical biomembrane elastic model is constructed to describe biomembrane mechanical properties. The characterized elastic modulus of embryos is 2.3 times that of oocytes, and the measured forces for puncturing embryo ZP are 1.7 times those for oocyte ZP. The technique and model presented in this paper can be applied to investigations into the mechanical properties of other biomembranes, such as the plasma membrane of oocytes or other cell types.

Abstract: Tumor necrosis factor-alpha (TNF-alpha) is a potent cytokine with anticancer efficacy that can significantly enhance hyperthermic injury. However, TNF-alpha is systemically toxic, thereby creating a need for its selective tumor delivery. We used a newly developed nanoparticle delivery system consisting of 33-nm polyethylene glycol-coated colloidal gold nanoparticles (PT-cAu-TNF-alpha) with incorporated TNF-alpha payload (several hundred TNF-alpha molecules per nanoparticle) to maximize tumor damage and minimize systemic exposure to TNF-alpha. SCK mammary carcinomas grown in A/J mice were treated with 125 or 250 microg/kg PT-cAu-TNF-alpha alone or followed by local heating at 42.5 degrees C using a water bath for 60 minutes, 4 hours after nanoparticle injection. Increases in tumor growth delay were observed for both PT-cAu-TNF-alpha alone and heat alone, although the most dramatic effect was found in the combination treatment. Tumor blood flow was significantly suppressed 4 hours after an i.v. injection of free TNF-alpha or PT-cAu-TNF-alpha. Tumor perfusion, imaged by contrast enhanced ultrasonography, on days 1 and 5 after treatment revealed perfusion defects after the injection of PT-cAu-TNF-alpha alone and, in many regions, complete flow inhibition in tumors treated with combination treatment. The combination treatment of SCK tumors in vivo reduced the in vivo/in vitro tumor cell survival to 0.05% immediately following heating and to 0.005% at 18 hours after heating, suggesting vascular damage-mediated tumor cell killing. Thermally induced tumor growth delay was enhanced by pretreatment with TNF-alpha-coated gold nanoparticles when given i.v. at the proper dosage and timing.

Abstract: Protein stability is critical to the outcome of nearly all thermally mediated applications to biomaterials such as thermal therapies (including cryosurgery), burn injury, and biopreservation. As such, it is imperative to understand as much as possible about how a protein loses stability and to what extent we can control this through the thermal environment as well as through chemical or mechanical modification of the protein environment. This review presents an overview of protein stability in terms of denaturation due to temperature alteration (predominantly high and some low) and its modification by use of chemical additives, pH modification as well as modification of the mechanical environment (stress) of the proteins such as collagen. These modifiers are able to change the kinetics of protein denaturation during heating. While pH can affect the activation energy (or activation enthalpy) and the frequency factor (or activation entropy) of the denaturation kinetics, many other chemical and mechanical modifiers only affect the frequency factor (activation entropy). Often, the modification affecting activation entropy appears to be linked to the hydration of the protein. While the heat-induced denaturation of proteins is reasonably well understood, the heat denaturation of structural proteins (e.g., collagen) within whole tissues remains an area of active research. In addition, while some literature exists on protein denaturation during cold temperatures, relatively little is known about the kinetics of protein denaturation during both freezing and drying. Further understanding of this kinetics will have an important impact on applications ranging from preservation of biomaterials and pharmaceutics to cryosurgery. Interestingly, both freezing and drying involve drastic shifts in the hydration of the proteins. It is clear that understanding protein hydration at the molecular, cellular, and tissue level will be important to the future of this evolving area.

Abstract: This review focuses on the synthesis, protection, functionalization, and application of magnetic nanoparticles, as well as the magnetic properties of nanostructured systems. Substantial progress in the size and shape control of magnetic nanoparticles has been made by developing methods such as co-precipitation, thermal decomposition and/or reduction, micelle synthesis, and hydrothermal synthesis. A major challenge still is protection against corrosion, and therefore suitable protection strategies will be emphasized, for example, surfactant/polymer coating, silica coating and carbon coating of magnetic nanoparticles or embedding them in a matrix/support. Properly protected magnetic nanoparticles can be used as building blocks for the fabrication of various functional systems, and their application in catalysis and biotechnology will be briefly reviewed. Finally, some future trends and perspectives in these research areas will be outlined.

Abstract: Thermal energy storage in general, and phase change materials (PCMs) in particular, have been a main topic in research for the last 20 years, but although the information is quantitatively enormous, it is also spread widely in the literature, and difficult to find. In this work, a review has been carried out of the history of thermal energy storage with solid–liquid phase change. Three aspects have been the focus of this review: materials, heat transfer and applications. The paper contains listed over 150 materials used in research as PCMs, and about 45 commercially available PCMs. The paper lists over 230 references.

Abstract: This Perspective explores and explains the fundamental dogma of nanoparticle delivery to tumours and answers two central questions: ‘how many nanoparticles accumulate in a tumour?’ and ‘how does this number affect the clinical translation of nanomedicines?’

Abstract: This critical review provides an overall survey of the basic concepts and up-to-date literature results concerning the very promising use of gold nanoparticles (AuNPs) for medicinal applications. It includes AuNP synthesis, assembly and conjugation with biological and biocompatible ligands, plasmon-based labeling and imaging, optical and electrochemical sensing, diagnostics, therapy (drug vectorization and DNA/gene delivery) for various diseases, in particular cancer (also Alzheimer, HIV, hepatitis, tuberculosis, arthritis, diabetes) and the essential in vitro and in vivo toxicity. It will interest the medicine, chemistry, spectroscopy, biochemistry, biophysics and nanoscience communities (211 references).

Abstract: The use of lasers, over the past few decades, has emerged to be highly promising for cancer therapy modalities, most commonly the photothermal therapy method, which employs light absorbing dyes for achieving the photothermal damage of tumors, and the photodynamic therapy, which employs chemical photosensitizers that generate singlet oxygen that is capable of tumor destruction. However, recent advances in the field of nanoscience have seen the emergence of noble metal nanostructures with unique photophysical properties, well suited for applications in cancer phototherapy. Noble metal nanoparticles, on account of the phenomenon of surface plasmon resonance, possess strongly enhanced visible and near-infrared light absorption, several orders of magnitude more intense compared to conventional laser phototherapy agents. The use of plasmonic nanoparticles as highly enhanced photoabsorbing agents has thus introduced a much more selective and efficient cancer therapy strategy, viz. plasmonic photothermal therapy (PPTT). The synthetic tunability of the optothermal properties and the bio-targeting abilities of the plasmonic gold nanostructures make the PPTT method furthermore promising. In this review, we discuss the development of the PPTT method with special emphasis on the recent in vitro and in vivo success using gold nanospheres coupled with visible lasers and gold nanorods and silica-gold nanoshells coupled with near-infrared lasers.