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Calreticulin (CRT) on the cell surface that acts as an "eat me" signal is vital for macrophage-mediated programmed cell removal. The polyhydroxylated fullerenol nanoparticle (FNP) has appeared as an effective inducer to cause CRT exposure on cancer cell surface, but it failed in treating some cancer cells such as MCF-7 cells based on previous findings. Here, we carried out the 3D culture of MCF-7 cells, and interestingly found that the FNP induced CRT exposure on cells in 3D spheres via re-distributing CRT from endoplasmic reticulum (ER) to cell surface. Phagocytosis experiments in vitro and in vivo illustrated the combination of FNP and anti-CD47 monoclonal antibody (mAb) further enhanced macrophage-mediated phagocytosis to cancer cells. The maximal phagocytic index in vivo was about three times higher than that of the control group. Moreover, in vivo tumorigenesis experiments in mice proved that FNP could regulate the progress of MCF-7 cancer stem-like cells (CSCs). These findings expand the application of FNP in tumor therapy of anti-CD47 mAb and 3D culture can be used as a screening tool for nanomedicine. [Display omitted] • Fullerenol nanoparticle (FNP) reduces the toxicity of anti-CD47 antibodies therapy. • 3D culture enhances the sensitivity of MCF-7 cells to FNP. • FNP inhibits the progression of MCF-7 cancer stem cells. [ABSTRACT FROM AUTHOR]

In the past few years, protein hydrogels have attracted more and more attention due to their unique physical, chemical and biological properties. They have a more complex molecular structure than traditional polymer hydrogels, which leads to special properties like excellent biocompatibility, biodegradability and responsiveness. The proteins used to construct hydrogels have similar structure and function with proteins in human body, which is an excellent bio-derived material with potential biological activities. Therefore, through the study of the flexible and diverse assembly mechanism of protein hydrogels, we can understand their special properties. This allows it to be used to construct rich and diverse biomaterials with a wide range of application prospect. In this review, we summarized the research progress of protein hydrogels. The different assembly mechanisms were briefly described, including self-assembly and co-assembly. Then we introduced properties based on protein, including responsiveness, adhesion property, biocompatibility, conductivity, self-healing and mechanical property. In addition, the applications of protein hydrogels in wound dressings, drug delivery, bioadhesion, and biosensing were reviewed. Finally, we summarized the current challenges in the field of protein hydrogels. The future development prospects in biomedicine, tissue repair, biosensing and so on were also prospected. [Display omitted] • Different assembly mechanisms of protein hydrogels were introduced. • Properties of protein hydrogels were summarized in detail. • Biological applications of protein hydrogels were elaborated. • Superiority of protein hydrogels compared to other hydrogels was described. [ABSTRACT FROM AUTHOR]