Fibronectin (FN) is an endogenous protein rich in the RGD sequence, which has anti-inflammatory and antioxidant functions. However, due to its limited intracellular endocytosis ability, FN alone is difficult to achieve the ideal effect in disease treatment. Our group has combined FN and nanotechnology to develop nanomedicines for the treatment of cancer and inflammation diseases. In the field of cancer theranostics, we have constructed a metal- polyphenol network platform loaded with anticancer drug doxorubicin and coated with FN, which targets tumor cells with high expression of αvβ3 integrin. This platform was used for magnetic resonance imaging-guided tumor chemotherapy/chemodynamic therapy/immunotherapy, resulting in enhanced immunogenic cell death along with the PD-L1 antibody-mediated immune checkpoint blockade [1]. In terms of inflammation treatment, we prepared generation 5 poly(amidoamine) dendrimers functionalized with phenylboronic acid as a nanocarrier to achieve efficient intracellular FN delivery, thus promoting macrophage polarization towards M2 anti-inflammatory phenotype to inhibit activation of NF-κB inflammatory pathway, reducing secretion of inflammatory factors, and alleviating intracellular reactive oxygen species level. In vivo experiments were conducted using an acute lung injury (ALI) mouse model, and it was found that this FN delivery strategy can alleviate ALI symptoms by reducing lung inflammation and oxidative stress, which is expected to be a new strategy for dealing with different inflammatory diseases [2]. Furthermore, we used bioactive phosphorus dendrimers as a carrier system to load FN for the treatment of different inflammatory diseases (including gouty arthritis [3], osteoarthritis [4], Parkinson's disease [5]), and achieved ideal therapeutic effects in mouse models, providing a theoretical basis for further clinical translation. 

Acknowledgments: This work was financially supported by the National Key R&D Program (2022YFE0196900), and the Science and Technology Commission of Shanghai Municipality (23520712500, 21490711500, and 20DZ2254900). X.S. thanks the support by the Fundação para a Ciência e a Tecnologia (FCT) with Portuguese Government funds through the CQM Base Fund - UIDB/00674/2020 (DOI: 10.54499/UIDB/00674/2020) and Programmatic Fund - UIDP/00674/2020 (DOI: 10.54499/UIDP/00674/2020). 

References
[1] Xu, Y. et al. ACS Nano 2022, 16, 984-996;
[2] Gao, Y. et al. Biomacromolecules 2023, 24, 886-895; 
[3] Sun, H. X. et al. ACS Nano 2024, 18, 2195-2209; 
[4] Zhan, M. S. et al. ACS Nano 2024, 18, 10625–10641; 
[5] Dai, W. C. et al. Bioact. Mater. 2024, 38, 45-54