Progress in nanotechnology has enabled us to open many new fronts in biomedical research by exploiting the peculiar properties of materials at the nanoscale. The thermal sensitivity of certain materials is a highly valuable property because it can be exploited in many promising applications, such as thermo-sensitive drug or gene delivery systems, thermotherapy, thermal biosensors, imaging, and diagnosis. This review focuses on recent advances in thermo-sensitive nanomaterials of interest in biomedical applications. We provide an overview of the different kinds of thermoresponsive nanomaterials, discussing their potential and the physical mechanisms behind their thermal response. We thoroughly review their applications in biomedicine and finally discuss the current challenges and future perspectives of thermal therapies.

Background: Despite all the advances achieved in the field of tumor-biology research, in most cases conventional therapies including chemotherapy are still the leading choices. The main disadvantage of these treatments, in addition to the low solubility of many antitumor drugs, is their lack of specificity, which leads to the occurrence of severe side effects due to nonspecific drug uptake by healthy cells. Objective: The purpose of this manuscript is to review and analyze the recent progress made in cancer nanotherapy. Results: Progress in nanotechnology and its application in medicine have provided new opportunities and different smart systems. Such systems can improve the intracellular delivery of the drugs due to their multifunctionality and targeting potential. First, we provide a global overview of cancer and different smart nanoparticles currently used in oncology. Then, we analyze in detail the development of drug-delivery strategies in cancer therapy, focusing mainly on the intravenously administered smart nanoparticles. Finally, we discuss the challenges, clinical trials, marketed nanomedicines and future directions of the nanotherapy applied to cancer treatment. Conclusión: In this review, we have evidenced the tremendous potential that smart drug-delivery systems have to enhance the therapeutic effect of current standard treatment modalities, including chemotherapies and radiotherapies.

Currently, we are facing increasing demand to develop efficient systems for the detection and treatment of diseases that can realistically improve distinct aspects of healthcare in our society. Sensitive nanomaterials that respond to environmental stimuli can play an important role in this task. In this manuscript, we review the clinical trials carried out to date on thermosensitive nanomaterials, including all those clinical trials in hybrid nanomaterials that respond to other stimuli (e.g., magnetic, infrared radiation, and ultrasound). Specifically, we discuss their use in diagnosis and treatment of different diseases. At present, none of the existing trials focused on diagnosis take advantage of the thermosensitive characteristics of these nanoparticles. Indeed, almost all clinical trials consulted explore the use of Ferumoxytol as a current imaging test enhancer. However, the thermal property is being further exploited in the field of disease treatment, especially for the delivery of antitumor drugs. In this regard, ThermoDox®, based on lysolipid thermally sensitive liposome technology to encapsulate doxorubicin (DOX), is the flagship drug. In this review, we have evidenced the discrepancy existing between the number of published papers in thermosensitive nanomaterials and their clinical use, which could be due to the relative novelty of this area of research; more time is needed to validate it through clinical trials. We have no doubt that in the coming years there will be an explosion of clinical trials related to thermosensitive nanomaterials that will surely help to improve current treatments and, above all, will impact on patients’ quality of life and life expectancy.

Lipid nanocapsules (NCs) represent promising tools in clinical practice for diagnosis and therapy applications. However, the NC appropriate functionalization is essential to guarantee high biocompatibility and molecule loading ability. In any medical application, the immune system-impact of differently functionalized NCs still remains to be fully understood. A comprehensive study on the action exerted on human peripheral blood mononuclear cells (PBMCs) and major immune subpopulations by three different NC coatings: pluronic, chitosan and polyethylene glycol-polylactic acid (PEG) is reported. After a deep particle characterization, the uptake was assessed by flow-cytometry and confocal microscopy, focusing then on apoptosis, necrosis and proliferation impact in T cells and monocytes. Cell functionality by cell diameter variations, different activation marker analysis and cytokine assays were performed. We demonstrated that the NCs impact on the immune cell response is strongly correlated to their coating. Pluronic-NCs were able to induce immunomodulation of innate immunity inducing monocyte activations. Immunomodulation was observed in monocytes and T lymphocytes treated with Chitosan-NCs. Conversely, PEG-NCs were completely inert. These findings are of particular value towards a pre-selection of specific NC coatings depending on biomedical purposes for pre-clinical investigations;i.e.the immune-specific action of particular NC coating can be excellent for immunotherapy applications.