Clinical investigations have shown that a nonimmunogenic “cold” tumor is usually accompanied by few immunopositive cells and more immunosuppressive cells in the tumor microenvironment (TME), which is still the bottleneck of immune activation. Here, a fluorine assembly nanocluster was explored to break the shackles of immunosuppression, reawaken the immune system, and turn the cold tumor “hot.” Once under laser irradiation, FS@PMPt produces sufficient reactive oxygen species (ROS) to fracture the ROS-sensitive linker, thus releasing the cisplatin conjugated PMPt to penetrate into the tumors and kill the regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Meanwhile, ROS will induce potent immunogenic cell death (ICD) and further promote the accumulation of dendritic cells (DCs) and T cells, therefore not only increasing the infiltration of immunopositive cells from the outside but also reducing the immunosuppressive cells from the inside to break through the bottleneck of immune activation. The FS@PMPt nanocluster regulates the immune process in TME from negative to positive, from shallow to deep, to turn the cold tumor into a hot tumor and provoke a robust antitumor immune response.

Lung metastatic osteosarcoma is a lethal disease afflicting children and adolescents, with a 5-year survival rate of less than 20%. The development of perfluorocarbon (PFC) nanoemulsions as systems for direct pulmonary delivery of combination drug/siRNA therapy is reported. Fluorinated polycation (F-PCX) with an inherent ability to inhibit C-X-C receptor type 4 (CXCR4) is synthesized and used as a surfactant in the preparation of F-PCX@PFC nanoemulsions. The nanoemulsions are loaded with siRNA against signal transducer and activator of transcription 3 (STAT3) for combined treatment of lung metastasis in osteosarcoma. Intratracheal instillation of the treatments significantly prolonged the survival of animals with established lung metastases. The treatment with F-PCX@PFC/siSTAT3 emulsion polyplexes decreased the number of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in the tumors, while increasing CD8 + T cells infiltration andIFNγ secretion to overcome the immunosuppressive tumor microenvironment. The reported nanoemulsions represent a promising pulmonary treatment of lung metastatic osteosarcoma.

Self-assembled nanofibers hold tremendous promise for cancer theranostics owing to their in situ assembly, spatiotemporal responsiveness, and diverse bioactivity. Herein, this review summarizes recent advances of self-assembled peptide nanofibers and...

Neutrophil extracellular traps (NETs), consisting of chromatin DNA filaments coated with granule proteins, promote metastasis by enhancing tumor cell migration to distant organs. Recent studies indicate that NETs adhere to cancer cell membranes and enhance cell motility significantly to induce liver metastasis in patients with breast and colon cancers. Herein, a dynamically deformable protein delivery strategy is developed to prevent liver metastasis by disassembling NETs. Specifically, poly amino acid conjugating with polyethylene glycol (PAAP) is explored and synthesized for DNase-1 delivery. Notably, PAAP/DNase-1 degrades chromatin to induce apoptosis, followed by cell membrane rupture and remaining DNase-1 releases to the extracellular. More importantly, the released DNase-1 disassembles NET-DNA to prevent liver metastasis induced by NET. In all, PAAP/DNase-1 treatment not only suppresses tumor growth by degrading intracellular chromatin, but also prevents the liver metastasis by disassembling the NET-NDA. This strategy may provide brand-new inspiration to prevent the liver metastasis fundamentally in patients with metastatic colon and breast cancer.

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