ABSTRACT
Malignant tumors represent a formidable global health challenge, compelling the pursuit of innovative treatment modalities. Oncolytic therapy has emerged as a promising frontier in antitumor strategies. However, both natural agents (such as oncolytic bacteria or viruses) and synthetic oncolytic peptides confront formidable obstacles in clinical trials, which include the delicate equilibrium between safety and efficacy, the imperative for systemic administration with targeted therapy, and the need to counteract oncolysis-induced immunosuppression. To overcome these dilemmas, we have developed biomimetic nanoengineering to create oncolytic bacteria-inspired nanosystems (OBNs), spanning from hierarchical structural biomimicry to advanced bioactive biomimicry. Our OBNs harbor inherent oncolytic potential, including functionalized oligosaccharides mimicking bacterial cell walls for optimal blood circulation and tumor targeting, tumor acidity-switchable decoration for tumor-specific oncolysis, stereospecific tryptophan-rich peptides for robust oncolytic activity, encapsulated tumor immunomodulators for enhanced immunotherapy, and innate multimodal imaging potential for biological tracing. This work elucidates the efficacy and mechanisms of OBNs, encompassing primary tumor suppression, metastasis prevention, and recurrence inhibition. Systemic administration of d-chiral OBNs has demonstrated superior oncolytic efficacy, surpassing intratumoral injections of clinical-grade oncolytic peptides. This work heralds an era in biomimetic engineering on oncolytic agents, promising the revolutionization of contemporary oncolytic therapy paradigms for clinical translation.
Subject(s)
Neoplasms , Oncolytic Virotherapy , Oncolytic Viruses , Humans , Oncolytic Virotherapy/methods , Immunomodulation , Neoplasms/therapy , Neoplasms/pathology , Immunotherapy/methods , Peptides , Tumor MicroenvironmentABSTRACT
Cellulose-dissolving ionic liquids (ILs) have been used in biomass pretreatment for over a decade. Cellulose solubility in the ILs is strongly inhibited by water, which has negative impacts on IL pretreatment and reuse of the recycled ILs. Here, a distillation and aeration apparatus was used as the reactor for biomass pretreatment in dilute aqueous IL solutions and in recycled IL liquor without drying or purification. Four biomass types, switchgrass, miscanthus, sorghum and pine, were studied. X-ray diffraction (XRD) was used to measure the interaction between biomass and the IL. Small angle neutron scattering (SANS) was applied to monitor the changes of the pore structure in wet biomass samples. Satisfactory enzymatic hydrolysis results were obtained among all the pretreated samples.