Da Zhang

Received March 14, 2005; revised manuscript received May 4, 2005; accepted May 4, 2005 We report what is believed to be the first experimental demonstration of two-photon correlated imaging with true thermal light from a hollow cathode lamp. The coherence time of the source is much shorter than that of previous experiments using random scattered light from a laser. A two-pinhole mask was used as object, and the corresponding thin lens equation was well satisfied. Since thermal light sources are easier to obtain and measure than entangled light, it is conceivable that they may be used in special imaging applications.

Photodynamic therapy (PDT), using a combination of chemical photosensitizers (PS) and light, has been successfully applied as a noninvasive therapeutic procedure to treat tumors by inducing apoptosis or necrosis of cancer cells. However, most current clinically used PS have suffered from the instability in physiological conditions which lead to low photodynamic therapy efficacy. Herein, a highly biocompatible poly(dopamine) (PDA) nanoparticle conjugated with Chlorin e6 (referenced as the PDA-Ce6 nanosphere) was designed as a nanotherapeutic agent to achieve simultaneous photodynamic/photothermal therapy (PDT/PTT). Compared to the free Ce6, the PDA-Ce6 nanosphere exhibited significantly higher PDT efficacy against tumor cells, because of the enhanced cellular uptake and subsequently greater reactive oxygen species (ROS) production upon laser irradiation at 670 nm. Meanwhile, the PDA-Ce6 nanosphere could be also used as a photoabsorbing agent for PTT, because of the excellent photothermal conversion ability of PDA nanoparticle under laser irradiation at 808 nm. Moreover, our prepared nanosphere had extremely low dark toxicity, while excellent phototoxicity under the combination laser irradiation of 670 and 808 nm, both in vitro and in vivo, compared to any single laser irradiation alone. Therefore, our prepared PDA-Ce6 nanosphere could be applied as a very promising dual-modal phototherapeutic agent for enhanced cancer therapy in future clinical applications.

PURPOSE: To objectively characterize the performance of the gemstone spectral imaging (GSI) mode of GE CT750 HD scanner from a user's perspective. METHODS: A regular scan protocol that approximates the adult abdomen scan protocol frequently used in the authors' institute was selected as the baseline, and a GSI protocol (preset 11) that is similar to the regular protocol and has a moderate dose level (CTDI(vol) = 26.27 mGy) was compared to the baseline protocol. The resolving power of both protocols was characterized in terms of modulation transfer functions and high contrast resolution bar readings. Their noise characteristics were studied through noise power spectra, and their low contrast detectability was compared via contrast-to-noise ratio. Material decomposition capability of GSI was evaluated by scanning iodine solutions of 9-24 mg/ml iodine concentration in a Gammex CT phantom and by examining the estimated iodine concentration. In addition, a formula describing the dependency of HU in iodine enhanced area on GSI monochromatic energies and iodine concentrations was provided and the theoretical values were compared with the measured results. RESULTS: The resolutions levels of 50%, 10%, and 5% MTF of GSI monochromatic images at 65 keV agree with those of the regular protocol within 0.1 1p/cm. GSI monochromatic images at 65 keV demonstrated the lowest noise level among GSI images of different monochromatic energies and showed very similar noise magnitude and noise power distribution as compared to the regular protocol images. The CNR of 60 and 65 keV GSI monoimages are approximately 100% of those of the regular protocol images. Estimated iodine concentration levels agreed with the actual values within 2% when the iodine solutions were placed at 3, 9, 12 o'clock positions of the phantom; when iodine solutions were placed at the phantom center and at 6 o'clock position, higher discrepancies of 2%-10% were observed. The observed dependency of HU on keV and iodine concentration levels agreed with the expectation from x-ray attenuations. CONCLUSIONS: Equivalent performances were observed in the comparison between GSI 65 keV monochromatic images and images from a regular abdomen scan protocol. This suggests the possibility of GSI to be employed in routine abdominal scans, which would potentially offer more information through its capabilities of material decomposition.

Subcellular organelles play critical roles in cell survival. In this work, a novel photodynamic therapy (PDT) drug delivery and phototoxicity on/off nano-system based on graphene oxide (NGO) as the carrier is developed to implement subcellular targeting and attacking. To construct the nanodrug (PPa-NGO-mAb), NGO is modified with the integrin αvβ3 monoclonal antibody (mAb) for tumor targeting. Pyropheophorbide-a (PPa) conjugated with polyethylene-glycol is used to cover the surface of the NGO to induce phototoxicity. Polyethylene-glycol phospholipid is loaded to enhance water solubility. The results show that the phototoxicity of PPa on NGO can be switched on and off in organic and aqueous environments, respectively. The PPa-NGO-mAb assembly is able to effectively target the αvβ3-positive tumor cells with surface ligand and receptor recognition; once endocytosized by the cells, they are observed escaping from lysosomes and subsequently transferring to the mitochondria. In the mitochondria, the 'on' state PPa-NGO-mAb performs its effective phototoxicity to kill cells. The biological and physical dual selections and on/off control of PPa-NGO-mAb significantly enhance mitochondria-mediated apoptosis of PDT. This smart system offers a potential alternative to drug delivery systems for cancer therapy.

Herein, we propose an aptamer-equipping strategy to generate specific, universal and permeable (SUPER) NK cells for enhanced immunotherapy in solid tumors. NK cells were chemically equipped with TLS11a aptamer targeting HepG2 cells and PDL1-specific aptamer without genetic alteration. The dual aptamer-equipped NK cells exhibited high specificity to tumor cells, resulting in higher cytokine secretion and apoptosis/necrosis compared to parental or single aptamer-equipped NK cells. Interestingly, dual aptamer-equipped NK cells induced remarkable upregulation of PDL1 expression in HepG2 cells, enhancing checkpoint blockade. Furthermore, in vivo intravital imaging demonstrated high infiltration of aptamer-equipped NK cells into deep tumor region, leading to enhanced therapeutic efficacy in solid tumors. This work offers a straightforward chemical strategy to equip NK cells with aptamers, holding considerable potential for enhanced adoptive immunotherapy in solid tumors.