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Although interest and funding in nanotechnology for oncological applications is thriving, translating these novel therapeutics through the earliest stages of preclinical assessment remains challenging. Upon intravenous administration, nanomaterials interact with constituents of the blood inducing a wide range of associated immunotoxic effects. The literature on the immunological interactions of nanomaterials is vast and complicated. A small change in a particular characteristic of a nanomaterial (e.g., size, shape, or charge) can have a significant effect on its immunological profile in vivo, and poor selection of specific assays for establishing these undesirable effects can overlook this issue until the latest stages of preclinical assessment. This work describes the current literature on unintentional immunological effects associated with promising cancer nanomaterials (liposomes, dendrimers, mesoporous silica, iron oxide, gold, and quantum dots) and puts focus on what is missing in current preclinical evaluations. Opportunities for avoiding or limiting immunotoxicity through efficient preclinical assessment are discussed, with an emphasis placed on current regulatory views and requirements. Careful consideration of these issues will ensure a more efficient preclinical assessment of cancer nanomedicines, enabling a smoother clinical translation with less failures in the future.

Heat has been used to treat tumors for thousands of years. There are reports of the Egyptians and Greek philosophers using such treatments as far back as 3000 BC and 500 BC respectively for various solid tumors. Albeit, in these cases, the treatment was not very controlled and consisted of hot sticks or blades placed against tissue in order to thermally ablate the tumor. It was not until recent times that the application of heat through various mediums enabled a more controlled, localized, and consistent method of treating tumors. While the therapeutic potential of this treatment has become more apparent, the mechanisms related to its efficacy are only recently beginning to surface. This review discusses the evidence associated with the effects of localized heat on the hallmarks of cancer. Key literature describing modulations to vasculature, cell viability, DNA damage and repair, metabolism, immune system, and tumor metastasis in response to heat will be reviewed along with considerations for its optimal implementation in the clinic to enhance the efficacy of conventional treatments.

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