Nanomedicine and Hyperthermia for the Treatment of Gastrointestinal Cancer: A Systematic Review

Abstract

The incidence of gastrointestinal cancers has increased in recent years. Current treatments present numerous challenges, including drug resistance, non-specificity, and severe side effects, needing the exploration of new therapeutic strategies. One promising avenue is the use of magnetic nanoparticles, which have gained considerable interest due to their ability to generate heat in tumor regions upon the application of an external alternating magnetic field, a process known as hyperthermia. This review conducted a systematic search of in vitro and in vivo studies published in the last decade that employ hyperthermia therapy mediated by magnetic nanoparticles for treating gastrointestinal cancers. After applying various inclusion and exclusion criteria (studies in the last 10 years where hyperthermia using alternative magnetic field is applied), a total of 40 articles were analyzed. The results revealed that iron oxide is the preferred material for magnetism generation in the nanoparticles, and colorectal cancer is the most studied gastrointestinal cancer. Interestingly, novel therapies employing nanoparticles loaded with chemotherapeutic drugs in combination with magnetic hyperthermia demonstrated an excellent antitumor effect. In conclusion, hyperthermia treatments mediated by magnetic nanoparticles appear to be an effective approach for the treatment of gastrointestinal cancers, offering advantages over traditional therapies.

Keywords: cytotoxic drugs; gastrointestinal cancer; hyperthermia; magnetic nanoparticles.

Figure 1

Flow diagram that represents the articles included in the systematic review.

Figure 2

Use of magnetic nanoparticles in in vitro AMF hyperthermia application experiments. Magnetic nanoparticles, typically composed of iron, can be functionalized with antibodies (against HER2, TAG72, or CD133) or specific peptides to actively target a tumor population. AMF facilitates, in formulations that encapsulate drugs, a greater drug release into the cell and the induction of heightened cellular stress. These factors ultimately result in the death of tumor cells, triggering the activation of PARP and the cleavage of several caspases to activate the apoptotic pathway.

Figure 3

Use of magnetic hypothermia in in vivo experiments. Typically, the assays involve an intravenous administration of the NPs into the mouse such that once they reach the tumor, they are capable of: (1) generating hyperthermia when exposed to an AMF, serving as an antitumor therapy alone or in combination with chemotherapeutic drugs; or (2) acting as contrast agents, creating negative contrast and potentially being used for tumor diagnosis and monitoring. Following the generation of hyperthermia, tumor cell death can occur through several pathways, with apoptosis, necrosis, or extensive oxidative stress being the most notable.