Conventional antibody-based targeted cancer therapy is one of the most promising avenues of successful cancer treatment, with the potential to reduce toxic side effects to healthy cells surrounding tumor cells. However, the full potential of antibodies is severely limited due to their large size, low stability, slow clearance, and high immunogenicity. Alternatively, recently discovered nanobodies, which are the smallest naturally occurring antigen-binding format, have shown great potential for addressing these limitations. Bioconjugation of nanobodies to functional groups such as toxins, enzymes, radionucleotides, and fluorophores can improve the efficacy and potency of nanobodies, enhance their in vivo pharmacokinetics, and expand the range of potential applications. Herein, we review the superior characteristics of nanobodies in comparison to conventional antibodies and provide insight into recent developments in nanobody conjugates for targeted cancer therapy and imaging.

The cause for at least 50% of recurrent miscarriages (RM) is unclear, defined as unexplained recurrent miscarriages (uRM). B7-H1 (PD-L1), a molecule of the B7 family, promotes tumor development by modulating immune evasion, and recent researchers have also attached importance to the role of B7-H3, another molecule of B7 family, in tumor. Based on the similarity between growth and immune response in tumors and pregnancy, we first explored the role of B7-H3 in uRM. We found reduced levels of B7-H3 in villus tissue of uRM patients, and it was mainly expressed on the cell membrane of extravillous trophoblasts (EVT). Further, the HTR-8/SVneo and JEG-3 cells were selected to explore the role of B7-H3 in proliferation, apoptosis, tube formation, migration, and invasion. We found that B7-H3 regulated trophoblast migration and invasion via RhoA/ROCK2 signaling pathway. Inflammatory cytokines were detected through ELISA after co-culturing with decidual natural killer cells (dNK) and B7-H3-knockout JEG-3. Results showed that B7-H3 inhibited IL-8 and IP-10 secretion from dNK. In a CBA/J × DBA/2 abortion-prone mice model, treatment with B7-H3-Fc protein successfully reduced the rate of embryo resorption. In conclusion, our results revealed a possible mechanism by which decreased B7-H3 on trophoblasts of uRM inhibited trophoblast migration and invasion and increased IL-8 and IP-10 secretion from dNK. Furthermore, B7-H3 may be a promising new therapeutic target in uRM patients.

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Premature ovarian failure (POF) and intrauterine adhesion (IUA) that easily lead to reduced fertility in premenopausal women are two difficult diseases to treat in obstetrics and gynecology. Hormone therapy, in vitro fertilization and surgical treatments do not completely restore fertility. The advent of hydrogels offers new hope for the treatment of POF and IUA. Hydrogels are noncytotoxic and biodegradable, and do not cause immune rejection or inflammatory reactions. Drug delivery and stem cell delivery are the main application forms. Hydrogels are a local drug delivery reservoir, and the control of drug release is achieved by changing the physicochemical properties. The porous properties and stable three-dimensional structure of hydrogels support stem cell growth and functions. In addition, hydrogels are promising biomaterials for increasing the success rate of ovarian tissue transplantation. Hydrogel-based in vitro three-dimensional culture of follicles drives the development of artificial ovaries. Hydrogels form a barrier at the site of injury and have antibacterial, antiadhesive and antistenosis properties for IUA treatment. In this review, we evaluate the physicochemical properties of hydrogels, and focus on the latest applications of hydrogels in POF and IUA. We also found the limitations on clinical application of hydrogel and provide future prospects. Artificial ovary as the future of hydrogel in POF is worth studying, and 3D bioprinting may help the mass production of hydrogels.