The carbohydrate antigens Tn and sialyl-Tn (STn) are expressed in most carcinomas and usually absent in healthy tissues. These antigens have been correlated with cancer progression and poor prognosis, and associated with immunosuppressive microenvironment. Presently they are used in clinical trials as therapeutic vaccination, but with limited success due to their low immunogenicity. Alternatively, anti-Tn and/or STn antibodies may be used to harness the immune system against tumor cells. Whilst the development of antibodies against these antigens had a boost two decades ago for diagnostic use, so far no such antibody entered into clinical trials. Possible limitations are the low specificity and efficiency of existing antibodies and that novel antibodies are still necessary. The vast array of methodologies available today will allow rapid antibody development and novel formats. Following the advent of hybridoma technology, the immortalization of human B cells became a methodology to obtain human monoclonal antibodies with better specificity. Advances in molecular biology including phage display technology for high throughput screening, transgenic mice and more recently molecularly engineered antibodies enhanced the field of antibody production. The development of novel antibodies against Tn and STn taking advantage of innovative technologies and engineering techniques may result in innovative therapeutic antibodies for cancer treatment.
Iron oxide nanoparticles (NPs) have been extensively studied in the last few decades for several biomedical applications such as magnetic resonance imaging, magnetic drug delivery and hyperthermia. Hyperthermia is a technique used for cancer treatment which consists in inducing a temperature of about 41-45 °C in cancerous cells through magnetic NPs and an external magnetic field. Chemical precipitation was used to produce iron oxide NPs 9 nm in size coated with oleic acid and trisodium citrate. The influence of both stabilizers on the heating ability and in vitro cytotoxicity of the produced iron oxide NPs was assessed. Physicochemical characterization of the samples confirmed that the used surfactants do not change the particles' average size and that the presence of the surfactants has a strong effect on both the magnetic properties and the heating ability. The heating ability of Fe3O4 NPs shows a proportional increase with the increase of iron concentration, although when coated with trisodium citrate or oleic acid the heating ability decreases. Cytotoxicity assays demonstrated that both pristine and trisodium citrate Fe3O4 samples do not reduce cell viability. However, oleic acid Fe3O4 strongly reduces cell viability, more drastically in the SaOs-2 cell line. The produced iron oxide NPs are suitable for cancer hyperthermia treatment and the use of a surfactant brings great advantages concerning the dispersion of NPs, also allowing better control of the hyperthermia temperature.
Cancer is one of the main causes of death in the world and its incidence increases every day. Current treatments are insufficient and present many breaches. Hyperthermia is an old concept and since early it was established as a cancer treatment option, mainly in superficial cancers. More recently the concept of intracellular hyperthermia emerged wherein magnetic particles are concentrated at the tumor site and remotely heated using an applied magnetic field to achieve hyperthermic temperatures (42-45°C). Many patents have been registered in this area since the year 2000. This review presents the most relevant information, organizing them according to the hyperthermic method used: 1) external Radio-Frequency devices; 2) hyperthermic perfusion; 3) frequency enhancers; 4) apply heating to the target site using a catheter; 5) injection of magnetic and ferroelectric particles; 6) injection of magnetic nanoparticles that may carry a pharmacological active drug. The use of magnetic nanoparticles is a very promising treatment approach since it may be used for diagnostic and treatment. An ideal magnetic nanoparticle would be able to detect and diagnose the tumor, carry a pharmacological active drug to be delivered in the tumor site, apply hyperthermia through an external magnetic field and allow treatment monitoring by magnetic resonance imaging.
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