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.

Cell encapsulation in hydrogels has been extensively used in cytotherapy, regenerative medicine, 3D cell culture, and tissue engineering. Herein, we fabricated microencapsulated cells through microcapsules loaded with C5.18 chondrocytes alginate/chitosan prepared by a high-voltage electrostatic method. Under optimized conditions, microencapsulated cells presented uniform size distribution, good sphericity, and a smooth surface with different cell densities. The particle size distribution was determined at 150–280 μm, with an average particle diameter of 220 μm. The microencapsulated cells were cultured under static, shaking, and 3D micro-gravity conditions with or without bFGF (basic fibroblast growth factor) treatment. The quantified detection (cell proliferation detection and glycosaminoglycan (GAG)/type II collagen (Col-II)) content was respectively determined by cell counting kit-8 assay (CCK-8) and dimethylmethylene blue (DMB)/Col-II secretion determination) and qualitative detection (acridine orange/ethidium bromide, hematoxylin-eosin, alcian blue, safranin-O, and immunohistochemistry staining) of these microencapsulated cells were evaluated. Results showed that microencapsulated C5.18 cells under three-dimensional microgravity conditions promoted cells to form large cell aggregates within 20 days by using bFGF, which provided the possibility for cartilage tissue constructs in vitro. It could be found from the cell viability (cell proliferation) and synthesis (content of GAG and Col-II) results that microencapsulated cells had a better cell proliferation under 3D micro-gravity conditions using bFGF than under 2D conditions (including static and shaking conditions). We anticipate that these results will be a benefit for the design and construction of cartilage regeneration in future tissue engineering applications.