Significant Inhibition of Tumor Growth following Single Dose Nanoparticle-Enhanced Photodynamic Therapy

Photodynamic therapy (PDT) for cancer treatment involves the pathology’s uptake of photosensitizers, which produce cytotoxic reactive oxygen species by photoirradiation. The use of nanoparticles as carriers of photosensitizers is one promising approach to this endeavor, owing to their small size, unique physicochemical properties, and easy/diverse functionalization. In the current work, we report on the in vivo assessment of PDT efficacy of these nanoconstructs in a murine model of human breast cancer, following a single (one-shot) nanoparticle dose and photoirradiation. Palladium-porphyrin (PdTPP) was administered intratumorally via injection of aqueous suspensions of either free PdTPP or MSN-conjugated PdTPP (MSN-PdTPP) at a dose of 50 μg. Mice were then exposed to a single photoirradiation session with total energy of 80 J. One month after one-shot PDT treatment, significantly greater reductions in tumor growth were observed in MSN-Pd treated animals than in PdTPP cohorts. Electron microscopy of tumor specimens harvested at various timepoints revealed excellent MSN-PdTPP uptake by cancer cells while immunohistologic analysis demonstrated marked increases in apoptotic response of MSN-PdTPP treated animals relative to PdTPP controls. Taken together, these findings suggest that considerable improvements in PDT efficacy can readily be achieved via the use of nanoparticle-based photosensitizers

Modular detector systems for nuclear medicine imaging

Modular detectors provide system design flexibility that makes possible the development of many imaging systems not possible through the use of more traditional approaches such as employing fixed ring configurations or large FOV (field-of-view) detectors. We have developed two such modular detector systems. The first is a small FOV modular gamma camera based on a position-sensitive photomultiplier tube (PSPMT) and single contiguous NaI(Tl) scintillation crystal. This detector can be used, for example, in the development of systems for planar single-photon emission imaging and for single-photon emission computed tomography (SPECT). The second is a modular panel based on an array of small FOV photomultiplier tubes (PMTs) and a pixilated array of LSO crystals. This detector can be used in development of systems for positron emission tomography (PET). For each modular detector, special signal -processing and computer- interface electronics have been designed and implemented in conjunction with its own radiation shielding, crystal or crystal array, PSPMT or PMTs, and computing processors. Such modular detectors can be employed as components of general-purpose or application-specific emission imaging systems for human (clinical or research) imaging or for laboratory animal imaging. Applications for which systems with modular detectors may be relevant include diagnostic imaging of humans in specialized clinical procedures and research imaging of animals for drug discovery and development, and for biotechnology development. © 2004 IEEE

Recent Advances in Nanoparticle-Based Förster Resonance Energy Transfer for Biosensing, Molecular Imaging and Drug Release Profiling

Abstract: Förster resonance energy transfer (FRET) may be regarded as a “smart” technology in the design of fluorescence probes for biological sensing and imaging. Recently, a variety of nanoparticles that include quantum dots, gold nanoparticles, polymer, mesoporous silica nanoparticles and upconversion nanoparticles have been employed to modulate FRET. Researchers have developed a number of “visible ” and “activatable ” FRET probes sensitive to specific changes in the biological environment that are especially attractive from the biomedical point of view. This article reviews recent progress in bringing these nanoparticle-modulated energy transfer schemes to fruition for applications in biosensing, molecular imaging and drug delivery

X-ray Activated Nanoplatforms for Deep Tissue Photodynamic Therapy

Photodynamic therapy (PDT), the use of light to excite photosensitive molecules whose electronic relaxation drives the production of highly cytotoxic reactive oxygen species (ROS), has proven an effective means of oncotherapy. However, its application has been severely constrained to superficial tissues and those readily accessed either endoscopically or laparoscopically, due to the intrinsic scattering and absorption of photons by intervening tissues. Recent advances in the design of nanoparticle-based X-ray scintillators and photosensitizers have enabled hybridization of these moieties into single nanocomposite particles. These nanoplatforms, when irradiated with diagnostic doses and energies of X-rays, produce large quantities of ROS and permit, for the first time, non-invasive deep tissue PDT of tumors with few of the therapeutic limitations or side effects of conventional PDT. In this review we examine the underlying principles and evolution of PDT: from its initial and still dominant use of light-activated, small molecule photosensitizers that passively accumulate in tumors, to its latest development of X-ray-activated, scintillator–photosensitizer hybrid nanoplatforms that actively target cancer biomarkers. Challenges and potential remedies for the clinical translation of these hybrid nanoplatforms and X-ray PDT are also presented

X-ray Activated Nanoplatforms for Deep Tissue Photodynamic Therapy

Photodynamic therapy (PDT), the use of light to excite photosensitive molecules whose electronic relaxation drives the production of highly cytotoxic reactive oxygen species (ROS), has proven an effective means of oncotherapy. However, its application has been severely constrained to superficial tissues and those readily accessed either endoscopically or laparoscopically, due to the intrinsic scattering and absorption of photons by intervening tissues. Recent advances in the design of nanoparticle-based X-ray scintillators and photosensitizers have enabled hybridization of these moieties into single nanocomposite particles. These nanoplatforms, when irradiated with diagnostic doses and energies of X-rays, produce large quantities of ROS and permit, for the first time, non-invasive deep tissue PDT of tumors with few of the therapeutic limitations or side effects of conventional PDT. In this review we examine the underlying principles and evolution of PDT: from its initial and still dominant use of light-activated, small molecule photosensitizers that passively accumulate in tumors, to its latest development of X-ray-activated, scintillator–photosensitizer hybrid nanoplatforms that actively target cancer biomarkers. Challenges and potential remedies for the clinical translation of these hybrid nanoplatforms and X-ray PDT are also presented

Surface charge-mediated rapid hepatobiliary excretion of mesoporous silica nanoparticles

[[abstract]]Nanoparticle-assisted drug delivery has been emerging as an active research area in recent years. The in vivo biodistribution of nanoparticle and its following mechanisms of biodegradation and/or excretion determine the feasibility and applicability of such a nano-delivery platform in the practical clinical translation. In this work we report the synthesis of the highly positive charge, near-infrared fluorescent mesoporous silica nanoparticles (MSNs) that demonstrate rapid hepatobiliary excretion, for use as traceable drug delivery platforms of high capacity. MSNs were incorporated with near-infrared fluorescent dye indocyanine green (ICG) via covalent or ionic bonding, to derive comparable constructs of significantly different net surface charge. In vivo fluorescence imaging and subsequent inductively coupled plasma-mass spectroscopy of harvested tissues, urine, and feces revealed markedly different uptake and elimination behaviors between the two conjugations; with more highly charged moieties (+34.4?mV at pH 7.4) being quickly excreted from the liver into the gastrointestinal tract, while less charged moieties (-17.6?mV at pH 7.4) remained sequestered within the liver. Taken together, these findings suggest that charge-dependent adsorption of serum proteins greatly facilitates the hepatobiliary excretion of silica nanoparticles, and that nanoparticle residence time in vivo can be regulated by manipulation of surface charge