Conventional photothermal therapy (PTT) irradiates the tumor tissues by elevating the temperature above 48 °C to exert thermal ablation, killing tumor cells. However, thermal ablation during PTT harmfully damages the surrounding normal tissues, post-treatment inflammatory responses, rapid metastasis due to the short-term mass release of tumor-cellular contents, or other side effects. To circumvent this limitation, mild-temperature photothermal therapy (MTPTT) was introduced to replace PTT as it exerts its activity at a therapeutic temperature of 42–45 °C. However, the significantly low therapeutic effect comes due to the thermoresistance of cancer cells as MTPTT figures out some of the side-effects issues. Herein, our current review suggested the mechanism and various strategies for improving the efficacy of MTPTT. Especially, heat shock proteins (HSPs) are molecular chaperones overexpressed in tumor cells and implicated in several cellular heat shock responses. Therefore, we introduced some methods to inhibit activity, reduce expression levels, and hinder the function of HSPs during MTPTT treatment. Moreover, other strategies also were emphasized, including nucleus damage, energy inhibition, and autophagy mediation. In addition, some therapies, like radiotherapy, chemotherapy, photodynamic therapy, and immunotherapy, exhibited a significant synergistic effect to assist MTPTT. Our current review provides a basis for further studies and a new approach for the clinical application of MTPTT.

A dissolving microneedle patch for responsive insulin release and type 1 diabetes therapy.

Background: The traditional treatment for diabetes usually requires frequent insulin injections to maintain normoglycemia, which is painful and difficult to achieve blood glucose control. Results: To solve these problems, a non-invasive and painless oral delivery nanoparticle system with bioadhesive ability was developed by amphipathic 2-nitroimidazole–l-cysteine–alginate (NI–CYS–ALG) conjugates. Moreover, in order to enhance blood glucose regulation, an intelligent glucose-responsive switch in this nanoparticle system was achieved by loading with insulin and glucose oxidase (GOx) which could supply a stimulus-sensitive turnover strategy. In vitro tests illustrated that the insulin release behavior was switched “ON” in response to hyperglycemic state by GOx catalysis and “OFF” by normal glucose levels. Moreover, in vivo tests on type I diabetic rats, this system displayed a significant hypoglycemic effect, avoiding hyperglycemia and maintaining a normal range for up to 14 h after oral administration. Conclusion: The stimulus-sensitive turnover strategy with bioadhesive oral delivery mode indicates a potential for the development of synthetic GR-NPs for diabetes therapy, which may provide a rational design of proteins, low molecular drugs, as well as nucleic acids, for intelligent releasing via the oral route.