Nanoparticle-mediated thermal Cancer therapies: Strategies to improve clinical translatability

Despite significant advances, cancer remains a leading global cause of death. Current therapies often fail due to incomplete tumor removal and nonspecific targeting, spurring interest in alternative treatments. Hyperthermia, which uses elevated temperatures to kill cancer cells or boost their sensitivity to radio/chemotherapy, has emerged as a promising alternative. Recent advancements employ nanoparticles (NPs) as heat mediators for selective cancer cell destruction, minimizing damage to healthy tissues. This approach, known as NP hyperthermia, falls into two categories: photothermal therapies (PTT) and magnetothermal therapies (MTT). PTT utilizes NPs that convert light to heat, while MTT uses magnetic NPs activated by alternating magnetic fields (AMF), both achieving localized tumor damage. These methods offer advantages like precise targeting, minimal invasiveness, and reduced systemic toxicity. However, the efficacy of NP hyperthermia depends on many factors, in particular, the NP properties, the tumor microenvironment (TME), and TME-NP interactions. Optimizing this treatment requires accurate heat monitoring strategies, such as nanothermometry and biologically relevant screening models that can better mimic the physiological features of the tumor in the human body. This review explores the state-of-the-art in NP-mediated cancer hyperthermia, discussing available nanomaterials, their strengths and weaknesses, characterization methods, and future directions. Our particular focus lies in preclinical NP screening techniques, providing an updated perspective on their efficacy and relevance in the journey towards clinical trials.