Cuprotosis, a new type of cell death, provides great opportunities for the treatment of oral squamous cell carcinoma, as nanocarriers of copper ions can induce cuprotosis and immunogenic death. Here, we studied an editor that enables production of a nanoparticle “storm” in oral squamous cell carcinoma, maximizing the toxic effect of these particles and reprogramming the tumor microenvironment; as a result, T cells and natural killer (NK) cells can infiltrate the tumor microenvironment to activate an antitumor immune response. On this basis, the editor can be combined with optical therapy to improve patient prognosis. In this study, the metal ratio was regulated in response to the nanocarrier of acid response type. Thus, in the presence of a specific copper ion content, the nanocarrier could change the permeability of the tumor cell membrane. Based on these results, the nanoparticles were cracked in an acidic environment and then released copper ions. Finally, the nanoparticles contributed to cuprotosis and immunogenic death. In addition, the editor could inhibit murine oral cancer 1 (MOC1) tumors in C57BL/6 without toxicity. The rate of tumor growth inhibition was as high as approximately 80%. This strategy provides a new idea for immunotherapy. Moreover, it can improve the interaction between immunotherapy and the copper-induced death of oral squamous cell carcinoma. Above all, this study will provide a new opportunity for the effective treatment of oral squamous cell carcinoma.

The effective management of bacterial infections that are resistant to multiple drugs remains a substantial clinical challenge. The eradication of drug-resistant bacteria and subsequent promotion of angiogenesis are imperative for the regeneration of the infected wounds. Here, a novel and facile peptide containing injectable hydrogel with sustained antibacterial and angiogenic capabilities is developed. The antibacterial peptide that consists of 11 residues (CM11, WKLFKKILKVL) is loaded onto acrylate-modified gelatin through charge interactions. A vascular endothelial growth factor mimetic peptide KLT (KLTWQELYQLKYKGI) with a GCG (Gly-Cys-Gly) modification at the N-terminal is covalently coupled through a visible light-induced thiol-ene reaction. In this reaction, the acrylate gelatin undergoes cross-linkage within seconds. Based on the physical/chemical double crosslinking strategy, the bioactive peptides achieve sustained and sequential release. The results show that the hydrogel significantly inhibits methicillin-resistant Staphylococcus aureus (MRSA) growth through the rapid release of CM11 peptides at early stage; it forms obvious growth inhibition zones against pathogenic bacterial strains. Moreover, cell counting kit-8 assay and scratch test confirm that the CM11/KLT-functionalized hydrogels promote cell proliferation and migration through the later release of KLT peptides. In a mouse skin wound infected with self-luminous MRSA, the CM11/KLT-functionalized hydrogels enhance wound healing, with rapidly bacterial infection reduction, lower expression of inflammatory factors, and neovascularization promotion. These results suggest that the rationally designed, sustained and sequential release CM11/KLT-functionalized hydrogels have huge potential in promoting the healing of multi-drug resistant bacterial infected wounds.

Osteoarthritis is associated with the significantly increased friction of the joint, which results in progressive and irreversible damage to the articular cartilage. A synergistic therapy integrating lubrication enhancement and drug delivery is recently proposed for the treatment of early-stage osteoarthritis. In the present study, bioinspired by the self-adhesion performance of mussels and super-lubrication property of articular cartilages, a biomimetic self-adhesive dopamine methacrylamide–poly(2-methacryloyloxyethyl phosphorylcholine) (DMA–MPC) copolymer was designed and synthesized via free radical polymerization. The copolymer was successfully modified onto the surface of biodegradable mesoporous silica nanoparticles (bMSNs) by the dip-coating method to prepare the dual-functional nanoparticles (bMSNs@DMA–MPC), which were evaluated using a series of surface characterizations including the transmission electron microscope (TEM), Fourier transform infrared (FTIR) spectrum, thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), etc. The tribological test and in vitro drug release test demonstrated that the developed nanoparticles were endowed with improved lubrication performance and achieved the sustained release of an anti-inflammatory drug, i.e., diclofenac sodium (DS). In addition, the in vitro biodegradation test showed that the nanoparticles were almost completely biodegraded within 10 d. Furthermore, the dual-functional nanoparticles were biocompatible and effectively reduced the expression levels of two inflammation factors such as interleukin-1β (IL-1β) and interleukin-6 (IL-6). In summary, the surface functionalized nanoparticles with improved lubrication and local drug release can be applied as a potential intra-articularly injected biolubricant for synergistic treatment of early-stage osteoarthritis.