Nanoparticle mediated hyperthermia has been explored as a method to increase cancer treatment efficacy by heating tumours inside-out. With that purpose, nanoparticles have been designed and their properties tailored to respond to external stimuli and convert the supplied energy into heat, therefore inducing damage to tumour cells. Moreover, the combination of hyperthermia with chemotherapy has been described as a more effective strategy due to the synergy between the high temperature and the drug's effects, also associated with a remote controlled and on-demand drug release. In this review, the methods behind nanoparticle mediated hyperthermia, namely material design, external stimuli response and energy conversion will be discussed and critically analysed. We will address the most relevant studies on hyperthermia and temperature triggered drug release for cancer treatment. Finally, the advantages, difficulties and challenges of this therapeutic strategy will be discussed, while giving insight for future developments.

Bone tissue engineering emerged as a solution to treat critical bone defects, aiding in tissue regeneration and implant integration. Mainly, this field is based on the development of scaffolds and coatings that stimulate cells to proliferate and differentiate in order to create a biologically active bone substitute. In terms of materials, several polymeric and ceramic scaffolds have been developed and their properties tailored with the objective to promote bone regeneration. These scaffolds usually provide physical support for cells to adhere, while giving chemical and physical stimuli for cell proliferation and differentiation. Among the different cells that compose the bone tissue, osteoblasts, osteoclasts, stem cells, and endothelial cells are the most relevant in bone remodeling and regeneration, being the most studied in terms of scaffold–cell interactions. Besides the intrinsic properties of bone substitutes, magnetic stimulation has been recently described as an aid in bone regeneration. External magnetic stimulation induced additional physical stimulation in cells, which in combination with different scaffolds, can lead to a faster regeneration. This can be achieved by external magnetic fields alone, or by their combination with magnetic materials such as nanoparticles, biocomposites, and coatings. Thus, this review is designed to summarize the studies on magnetic stimulation for bone regeneration. While providing information regarding the effects of magnetic fields on cells involved in bone tissue, this review discusses the advances made regarding the combination of magnetic fields with magnetic nanoparticles, magnetic scaffolds, and coatings and their subsequent influence on cells to reach optimal bone regeneration. In conclusion, several research works suggest that magnetic fields may play a role in regulating the growth of blood vessels, which are critical for tissue healing and regeneration. While more research is needed to fully understand the relationship between magnetism, bone cells, and angiogenesis, these findings promise to develop new therapies and treatments for various conditions, from bone fractures to osteoporosis.

Controlled release of chemotherapeutic drugs is a key factor in cancer therapy. In this regard, temperature triggered release of drugs offers a precise control over the release within the tumour region, thus avoiding premature drug release and unspecific toxicity. In this work a novel polymeric N-isopropylacrylamide-based nanocarrier was developed to carry and release doxorubicin in response to the natural higher temperature of solid triple negative breast cancer tumours. The nanocarrier was further functionalized with folic acid moieties to improve the targeting of these cells. The obtained results show that the produced nanoparticles presented a thermoresponsive behaviour with a transition temperature of 42 °C. Moreover, a high drug loading was achieved (9.7%) followed by a sustained and temperature dependent drug release (55% at 37 °C and 86% at 40 °C). Regarding biosafety, the nanoparticles were cytocompatible up to a concentration of 5,000 µg mL ^− 1 , non-haemolytic, non-thrombogenic and anti-fouling, showing good properties to be intravenously administered. When tested against triple negative breast cancer cells in 2D models, a concentration and time dependent cytotoxic effect was observed, where folic acid-functionalized nanoparticles resulted in a lowering of the IC ₅₀ value in 77%, when compared with non-functionalized nanoparticles. Finally, a 3D in vitro model of the tumour was optimized, with the objective of better mimicking an in vivo scenario, where the NPs presented an effective tumour cell reduction in a temperature dependent manner. In conclusion, this work was able to optimize a novel nanoparticle to improve doxorubicin delivery in a controlled fashion, with specific targeting capabilities towards cancer cells, even in 3D systems where drug penetration is usually limited.