Classical reaction kinetics has been found to be unsatisfactory when the reactants are spatially constrained on the microscopic level by either walls, phase boundaries, or force fields. Recently discovered theories of heterogeneous reaction kinetics have dramatic consequences, such as fractal orders for elementary reactions, self-ordering and self-unmixing of reactants, and rate coefficients with temporal "memories." The new theories were needed to explain the results of experiments and supercomputer simulations of reactions that were confined to low dimensions or fractal dimensions or both. Among the practical examples of "fractal-like kinetics" are chemical reactions in pores of membranes, excitation trapping in molecular aggregates, exciton fusion in composite materials, and charge recombination in colloids and clouds.

X-ray based computed tomography (CT), is among the most convenient imaging/diagnostic tools in hospitals today in terms of availability, efficiency and cost. However, in contrast to magnetic resonance imaging (MRI) and various nuclear medicine imaging modalities, CT is not considered a molecular imaging modality since targeted and molecularly specific contrast agents have not yet been developed. Here we describe a targeted molecular imaging platform that enables, for the first time, cancer detection at the cellular and molecular level with standard clinical CT. The method is based on gold nano-probes that selectively and sensitively target tumor selective antigens, while inducing distinct contrast in CT imaging (increased x-ray attenuation). We present an in vitro proof of principle demonstration for head and neck cancer, showing that the attenuation coefficient for the molecularly targeted cells is over 5 times higher than for identical but untargeted cancer cells or for normal cells. We expect this novel imaging tool to lead to significant improvements in cancer therapy, due to earlier detection, accurate staging and micro-tumor identification.Imaging plays a critical role in overall cancer management; in diagnostics, staging, radiation planning and evaluation of treatment efficiency. Standard clinical imaging modalities such as CT, MRI and ultrasound, can be categorized as structural imaging modalities; they are able to identify anatomical patterns and to provide basic information regarding tumor location, size and spread based on endogenous contrast. However, these imaging modalities are not efficient in detecting tumors and metastases that are smaller than 0.5 cm, and they can barely distinguish between benign and cancerous tumors 1 .Molecular imaging is an emerging field that integrates molecular biology with in vivo imaging, in order to gain information regarding biological processes and to identify diseases based on molecular markers, which usually appear before the clinical presentation of the disease. Currently, positron emission tomography and single photon emission tomography are the main molecular imaging modalities in clinical use, however, they provide only functional information regarding molecular processes and metabolites, which is indirect and nonspecific to distinct cells or diseases 2,3 . Recently, various types of targeted nano-probes have been developed for optical and MRI molecular imaging, such as superparamagnetic nanoparticles 4-7 ; quantum dots [8][9][10] and gold nanoparticles as cancer optical imaging probes [11][12][13] .

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Purpose: Development of new therapeutic drug delivery systems is an area of significant research interest. The ability to directly target a therapeutic agent to a tumor site would minimize systemic drug exposure, thus providing the potential for increasing the therapeutic index. Experimental Design: Photodynamic therapy (PDT) involves the uptake of a sensitizer by the cancer cells followed by photoirradiation to activate the sensitizer. PDTusing Photofrin has certain disadvantages that include prolonged cutaneous photosensitization. Delivery of nanoparticles encapsulated with photodynamic agent specifically to a tumor site could potentially overcome the drawbacks of systemic therapy. In this study, we have developed a multifunctional polymeric nanoparticle consisting of a surface-localized tumor vasculature targeting F3 peptide and encapsulated PDTand imaging agents. Results:The nanoparticles specifically bound to the surface of MDA-435 cells in vitro and were internalized conferring photosensitivity to the cells. Significant magnetic resonance imaging contrast enhancement was achieved in i.c. rat 9L gliomas following i.v. nanoparticle administration. Serial magnetic resonance imaging was used for determination of pharmacokinetics and distribution of nanoparticles within the tumor. Treatment of glioma-bearing rats with targeted nanoparticles followed by PDT showed a significant improvement in survival rate when compared with animals who received PDT after administration of nontargeted nanoparticles or systemic Photofrin. Conclusions:This study reveals the versatility and efficacy of the multifunctional nanoparticle for the targeted detection and treatment of cancer.Photodynamic therapy (PDT) relies on the selective uptake of a photosensitizing molecule in a tumor relative to the surrounding normal parenchyma followed by exposure to the appropriate wavelength of light to activate the photosensitizer (1). When activated by light irradiation, the photosensitizer interacts with molecular oxygen to produce a cytotoxic, shortlived species known as singlet oxygen. PDT elicits both apoptotic and necrotic responses within treated tumors and produces microvascular injury leading to inflammation and hypoxia. Photofrin, a complex mixture of porphyrin oligomers, is one of the most efficient photosensitizers approved for PDT of cancer (2). However, Photofrin can cause prolonged skin photosensitization, where patients are required to avoid direct exposure to sunlight for a period of 4 to 6 weeks. Current strategies under development include attempts to direct the photosensitizing agent to the tumor by active targeting approaches, such as peptide conjugates and antibodies (3 -7), incorporation within liposomes (8, 9), and encapsulation within polymeric nanoparticles (10 -14) in an attempt to deliver higher local concentrations at the therapeutic site.A recent report of a sub-100 nm dynamic nanoparticle platform composed of polyacrylamide, which could be loaded with a photoactivatable agent (methylene blue) for the spe...

A new optical sensor based on covalent immobilization of a newly synthesized calcium-selective, long-wavelength, fluorescent indicator has been constructed, with a response dynamic range optimal for physiological measurements. Immobilization occurs via photoinitiated copolymerization of the indicator with acrylamide on the distal end of a silanized 125 micrograms diameter multimode optical fiber. The working lifetime of this sensor is limited only by photobleaching of the indicator. Due to the inherent hydrophilic nature of the acrylamide polymer, the response time of this new sensor is governed by simple aqueous diffusion of the ionic calcium. This results in sensor response times fast enough to monitor some concentration fluctuations at physiological rates. The ability to monitor calcium concentration fluctuations in a high background level of magnesium is also demonstrated with a calculated selectivity of 10(-4.5).