Journal of basic and clinical medicine最新文献

Surface modification of titanium dioxide (TiO₂) nanoparticle is essential to control its surface properties, thereby to enhance its cell penetration capability, reduce its cytotoxicity, or improve its biocompatibility. In order to graft polyvinyl acetate onto TiO₂ nanoparticles, xanthate was chemically immobilized on the surface of TiO₂ by acylation followed by nucleophilic substitution with a carbodithioate salt. Reversible addition fragmentation chain transfer polymerization was conducted to graft vinyl acetate onto the surface of TiO₂. Both the TiO₂-xanthate and TiO₂-polyvinyl acetate hybrids were characterized by UV-Vis spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The chemical immobilization of xanthate on the surface of TiO₂ and the subsequent controlled polymerization provide useful insight for decoration and modification of TiO₂ and other nanoparticles.

Immunotoxins are a group of protein-based therapeutics, basically comprising two functional moieties: one is the antibody or antibody Fv fragment that allows the immunotoxin to bind specifically to target cells; another is the plant or bacterial toxin that kills the cells upon internalization. Immunotoxins have several unique features which are superior to conventional chemotherapeutics, including high specificity, extraordinary potency, and no known drug resistance. Development of immunotoxins evolves with time and technology, but significant progress has been achieved in the past 20 years after introduction of recombinant DNA technique and generation of the first single-chain variable fragment of monoclonal antibodies. Since then, more than 1,000 recombinant immunotoxins have been generated against cancer. However, most success in immunotoxin therapy has been achieved against hematological malignancies, several issues persist to be significant barriers for effective therapy of human solid tumors. Further development of immunotoxins will largely focus on the improvement of penetration capability to solid tumor mass and elimination of immunogenicity occurred when given repeatedly to patients. Promising strategies may include construction of recombinant antibody fragments with higher binding affinity and stability, elimination of immunodominant T- and B-cell epitopes of toxins, modification of immunotoxins with macromolecules like poly(ethylene glycol) and liposomes, and generation of immunotoxins with humanized antibody fragments and human endogenous cytotoxic enzymes. In this paper, we briefly reviewed the evolution of immunotoxin development and then discussed the challenges of immunotoxin therapy for human solid tumors and the potential strategies we may seek to overcome the challenges.

Background: Hyperthermia is used in combination with radiotherapy and/or chemotherapy in the treatment of various types of cancer. Currently, the tumor cell response to hyperthermia is determined largely based on the size reduction of tumor mass, which is insensitive.

Methods: We tested the feasibility of bioluminescent imaging (BLI) in evaluation of the tumor cell response to hyperthermia by exposing luciferase-expressing MDA-MB-231-luc human breast cancer cells to high temperature (43 °C) for 10 minutes to 2 hours. The tumor cells were the imaged and the light signal generated by the tumor cells was quantified with BLI. To validate its usefulness, the light signal intensity was comparatively analyzed with the tumor cell clonogenicity and cell viability, which were measured with classic clonogenic and MTT assays.

Results: The light signal intensity determined by BLI was closely correlated with the absolute number of viable cells as well as the cell viability measured with the traditional MTT assay under normal culture condition. Relative to the clonogenicity of tumor cells after exposure to hyperthermia, however, BLI underestimated, while MTT assay overestimated the cell viability. Difference in the interpretation of tumor cell clonogenic ability following hyperthermia with BLI, MTT dye, and clonogenic assay may be due to the different mechanisms of the three measurements as well as the fact that hyperthermia can induce cell damage at levels of both transient and permanent.

Conclusions: BLI is sensitive, convenient, and potentially valuable in the evaluation and monitoring of tumor cell response to treatments including hyperthermia.

Personalized diagnosis and treatment with allogenic or autologous cells have been intensively investigated over the past decade. Despite the promising findings in preclinical studies, the clinical results to date have been largely disappointing. Some critical issues remain to be solved, such as how to monitor the migration, homing, survival, and function of the transplanted cells in vivo. In the past years, imaging techniques have been introduced to solve these issues based on a concept that cells can be transformed to a cellular imaging agent following labeling of the cells with an imaging agent. For this purpose, magnetic resonance imaging (MRI) is so far the first choice imaging modality and iron oxide-based nanoparticles are the most frequently applied labeling agents. However, most MRI cell tracking studies are currently still limited in in vivo visualization of the labeled cells, some critical elements for cell tracking studies are often incompletely characterized, which makes it difficult to validate and meta-analyze the data generated from different studies. Incomplete information on preclinical studies also slows the transition of the findings to clinical practice. A robust protocol of MRI cell tracking studies is apparently critical to deal with these issues. In this review, we first briefly discuss the limitations of MRI cell tracking based on iron oxide nanoparticles and then recommend a minimum set of essential elements that should be considered in MRI cell tracking studies at preclinical stage.