Functional organic nanoparticles for photodynamic therapy

In recent years, cancer has been one of the leading causes of death in the world. Much effort has been devoted to developing cancer treatments. Photodynamic therapy (PDT) is a noninvasive therapeutic modality by combining the light of a specific wavelength, a photosensitizer (PS) and oxygen, which has been widely applied for the treatment of cancers. However, the application of PDT in clinic is greatly limited due to lack of tumor selectivity and often causing skin photosensitivity. The use of organic nanoparticles (NPs) as an advanced technology in the field of PDT shows a great promise to overcome these shortcomings. Therefore, in this review, we summarize several functional organic NPs as PS carriers that have been developed to enhance the efficacy of PDT against cancers.     

Study of normal colorectal tissue by FT-Raman spectroscopy

FT-Raman spectroscopy was employed to study normal human colorectal tissues in vitro with the aim of evaluating the spectral differences of the complex colon mucous in order to establish a characteristic Raman spectrum. The samples were collected from 39 patients, providing 144 spectra for the statistical analysis. The results enable one to estabilish three well-defined spectroscopic groups of non-altered coloretal tissues that were consistently checked by statistical (clustering) and biological (histopathology) analyses: group 1 is represented by samples with the presence of epithelial layer, connective tissue papillae, and smooth muscle tissue; group 2 comprises tissues with epithelial layer and connective tissue papillae; group 3 presented mostly fatty and slack conjunctive tissue. The study reveals the existence of an intrinsic spectral variability for each patient that must be considered when sampling tissues fragments to build a spectral database. This is the first step for future studies and applications of Raman spectroscopy to optical biopsy and diagnosis of colorectal cancer.     

CH-overtone regions as diagnostic markers for near-infrared spectroscopic diagnosis of primary cancers in human pancreas and colorectal tissue

We have investigated the application of near-infrared spectroscopy for detection of human primary pancreatic and colorectal cancers. Spectra from cancerous and normal tissue were collected from a total of 37 surgically resected pancreatic and colorectal patient tissue specimens using a fibre-optic probe. Major spectral differences were observed in the CH-stretching first (6,000–5,400 cm⁻¹) and second overtone (9,000–7,900 cm⁻¹) regions. By use of artificial neural networks, linear discriminant analysis, and cluster analysis as pattern-recognition methods the spectra were classified into cancerous and normal tissue groups with accuracy up to 89%. We also explored differences between the spectra obtained from colorectal and pancreatic tissue. Spectral data from cancerous and normal tissue were classified organ-specifically into four groups with accuracy between 80 and 83%. Our results indicate that CH-overtone regions, besides serving as diagnostic markers for NIR spectroscopic diagnosis of primary human pancreas and colorectal cancers, are also useful for elucidating differences between the spectra obtained from colorectal and pancreatic cancerous tissue.     

Steep pulsed electric fields modulate cell apoptosis through the change of intracellular calcium concentration

A steep electric pulsed field with low intensity (150–250 V/cm) and relative long time (10 min) was applied to adherent liver cancer cell line SMMC-7721 and the liver cell line HL-7702. Results showed that the electric field with intensity of 200 and 250 V/cm could trigger cell apoptosis, whereas the SMMC-7721 cell was more sensitive to the electric stimulation than the HL-7702 cell. Laser Scanning Confocal Microscope (LSCM) was used to measuring the real-time change of cytosolic free Ca²⁺ concentration. When cells were exposed electric pulses with 100 V/cm intensity for 10 min, there was no significant change of intracellular calcium concentration. With the intensity increased to 200 and 250 V/cm, intracellular calcium concentration decreased significantly. Results demonstrated the relationship between the apoptosis and change of intracellular calcium concentration. And the steep electric pulsed field can be used to the cancer therapy.     

临床诊断试剂及其诊断方法研究进展

本文结合作者工作,综述了现代临床化学所用诊断试剂,以及诊断方法学研究的某些进展与发展趋向。     

Phosphate Coordination to Metal-Organic Layer Secondary Building Units Prolongs Drug Retention for Synergistic Chemoradiotherapy

Chemoradiotherapy combines radiotherapy with concurrent chemotherapy to potentiate antitumor activity but exacerbates toxicities and causes debilitating side effects in cancer patients. Herein, we report the use of a nanoscale metal-organic layer (MOL) as a 2D nanoradiosensitizer and a reservoir for the slow release of chemotherapeutics to amplify the antitumor effects of radiotherapy. Coordination of phosphate-containing drugs to MOL secondary building units prolongs their intratumoral retention, allowing for continuous release of gemcitabine monophosphate (GMP) for effective localized chemotherapy. In the meantime, the MOL sensitizes cancer cells to X-ray irradiation and provides potent radiotherapeutic effects. GMP-loaded MOL (GMP/MOL) enhances cytotoxicity by 2-fold and improves radiotherapeutic effects over free GMP in vitro. In a colon cancer model, GMP/MOL retains GMP in tumors for more than four days and, when combined with low-dose radiotherapy, inhibits tumor growth by 98 %. The synergistic chemoradiotherapy enabled by GMP/MOL shows a cure rate of 50 %, improves survival, and ameliorates cancer-proliferation histological biomarkers.     

Enhanced Survivin siRNA Delivery Using Cationic Liposome Incorporating Fatty Acid-modified Polyethylenimine

We described a novel approach for survivin siRNA cellular delivery via a cationic liposome incorporating fatty acid-modified polyethylenimine. A linoleic acid derivative of branched polyethylenimine(PEI, M_w=25 kDa), PEI-LA, was synthesized and incorporated into the liposome. The properties of the liposome, cytotoxicity, cellular uptake of cancer cells for survivin siRNA, survivin protein downregulation levels were investigated. PEI-modified liposome showed a lower cytotoxicity and delivered survivin siRNA into HeLa cells and A549 cells efficiently compared with PEI-25kDa.     

A multiphase model of tumour segregation in situ by a heterogeneous extracellular matrix

Normal and tumour cells live in a fibrous environment that is often very heterogeneous, even characterized by the presence of basal membranes and regions with high density of collagen fibres that physiologically comparmentalize cells in well defined regions, as for in situ tumours. In case of metastatic tumours these porous structures are instead invaded by cancer cells. The aim of this paper is to propose a multiphase model that is able to describe cell segregation by thick porous structures and to relate the transition rule that determines whether cells will pass or not to microscopic characteristics of the cells, such as the stiffness of their nucleus, their adhesive and traction abilities, the relative dimension of their nucleus with respect to the dimension of the pores of the extra-cellular matrix.     

A nonrigid registration algorithm for longitudinal breast MR images and the analysis of breast tumor response

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can estimate parameters relating to blood flow and tissue volume fractions and therefore may be used to characterize the response of breast tumors to treatment. To assess treatment response, values of these DCE-MRI parameters are observed at different time points during the course of treatment. We propose a method whereby DCE-MRI data sets obtained in separate imaging sessions can be co-registered to a common image space, thereby retaining spatial information so that serial DCE-MRI parameter maps can be compared on a voxel-by-voxel basis. In performing inter-session breast registration, one must account for patient repositioning and breast deformation, as well as changes in tumor shape and volume relative to other imaging sessions. One challenge is to optimally register the normal tissues while simultaneously preventing tumor distortion. We accomplish this by extending the adaptive bases algorithm through adding a tumor-volume preserving constraint in the cost function. We also propose a novel method to generate the simulated breast magnetic resonance (MR) images, which can be used to evaluate the proposed registration algorithm quantitatively. The proposed nonrigid registration algorithm is applied to both simulated and real longitudinal 3D high resolution MR images and the obtained transformations are then applied to lower resolution physiological parameter maps obtained via DCE-MRI. The registration results demonstrate the proposed algorithm can successfully register breast MR images acquired at different time points and allow for analysis of the registered parameter maps.     

Towards dynamic control of magnetic fields to focus magnetic carriers to targets deep inside the body

Magnetic drug delivery has the potential to target therapy to specific regions in the body, improving efficacy and reducing side effects for treatment of cancer, stroke, infection, and other diseases. Using stationary external magnets, which attract the magnetic drug carriers, this treatment is limited to shallow targets (<5 cm below skin depth using the strongest possible, still safe, practical magnetic fields). We consider dynamic magnetic actuation and present initial results that show it is possible to vary magnets one against the other to focus carriers between them on average. The many remaining tasks for deep targeting in-vivo are then briefly noted.