Cocktail nano-adjuvant enhanced cancer immunotherapy based on NIR-Ⅱ-triggered in-situ tumor vaccination

Second near-infrared(NIR-Ⅱ)light triggered in-situ tumor vaccination(ISTV)represents one of the most promising strategies in boosting the whole-body antitumor immunity.While most of previously developed nano-adjuvants for NIR-Ⅱ-triggered ISTV are“all-in-one”formulations,which may indiscriminately damage both the tumor cells and the immune cells,limiting the overall effect of immune response.To overcome this obstacle,we designed a“cocktail”nano-adjuvant by physically mixing hyaluronidases(HAase)-decorated gold nanostars(HA)for NIR-Ⅱlight triggered in situ production of tumor-associated antigens and CpG functionalized gold nanospheres(CA)for immune cells activation.Compared to“all-in-one”formulation,the“cocktail”nano-adjuvants displayed a significantly stronger immune response on NIR-Ⅱlight induced dendritic cells(DCs)mutation and T cells differentiation,greater effect on tumor-growth inhibition,and higher efficacy in inhibition of pulmonary metastases.What is more,increasing the molar ratio of HA to CA led to an enhanced anticancer immune responses.This study highlight the nano-adjuvant formulation effects on the treatment of tumors with multiple targets.

Lipase-activated glycopeptide nano-assemblies as an antibiotic nano-adjuvant to inhibit Pseudomonas aeruginosa biofilm and enhance antibacterial activity

Bacterial infections,especially those caused by biofilms,pose a serious threat to public health.In this work,we propose a glycopeptide-based antibiotic nano-adjuvant(GalAc-2) that can synergistically enhance the antibacterial activity of antibiotics through its biofilm inhibition activity.Our glycopeptide nanoparticles can be specifically activated by bacterial infection overexpressed lipase and sequentially enlarged by glycosyl exposure on the surface.The stability and bonding affinity of the nanoparticles were enhanced through the increase in β-sheet conformation.The bacterial growth inhibition rate of the mixture of levofloxacin(LEV) and GalAc-2 at 0.54 μg/m L was over sevenfold higher than that of LEV alone because of the electrostatic and multivalence Lec A interactions that inhibited biofilm formation on the bacterial surface.Finally,the mixture of the antibiotic with GalAc-2 significantly inhibited the abscess exposed to skin infection and significantly reduced the infiltration of immune cells.We believe that GalAc-2 can be further used to enhance broad-spectrum antibiotic sensitization and prolong the lifetime of antibiotics.