Evolution and Antigenic Differentiation of Avian Influenza A(H7N9) Virus, China.

We characterized the evolution and molecular characteristics of avian influenza A(H7N9) viruses isolated in China during 2021-2023. We systematically analyzed the 10-year evolution of the hemagglutinin gene to determine the evolutionary branch. Our results showed recent antigenic drift, providing crucial clues for updating the H7N9 vaccine and disease prevention and control.

Treatment of Lung Cancer by Peptide-Modified Liposomal Irinotecan Endowed with Tumor Penetration and NF-κB Inhibitory Activities.

Current chemotherapy for lung cancer achieved limited efficacy due to poor tumor targeting and tissue penetration. Another obstacle in the therapy is activated nuclear factor-κB (NF-κB) in tumor cells, which plays a crucial role in promotion of antiapoptosis and drug resistance. In this study, we utilized a multifunctional liposome loaded with irinotecan and surface modified with a cell-permeable NF-κB inhibitor (CB5005), for treatment of non-small-cell lung carcinoma. CB5005 downregulated the level of NF-κB-related protein in the nuclei of A549 cells, and increased cellular uptake of the modified liposomes. In vivo antitumor activity in mice bearing A549 xenografts revealed that modification with CB5005 significantly improved the tumor inhibition rate of irinotecan. Immunohistochemical assays showed that the tumors treated with CB5005-modified liposomes possessed the most apoptotic cells and the lowest level of p50 in the cell nuclei. These results strongly suggest that antitumor efficacy of the irinotecan liposomes can be enhanced by tumor-penetrating and NF-κB-inhibiting functions of CB5005. Consequently, CB5005-modified liposomes provide a possible synergistic therapy for lung cancer, and would also be appropriate for other types of tumors associated with elevated NF-κB activity.

Cell-permeable NF-κB inhibitor-conjugated liposomes for treatment of glioma.

Application of liposomes-based drug delivery in treatment of glioma has been hampered by the poor permeability of blood-brain barrier and the low uptake efficiency by glioma tissues. Moreover, many chemotherapy drugs promote the activation of the NF-κB, which plays a role in the development and progression of cancer and chemoresistance. In this report, CB5005 peptide, designed for its dual function in cell membrane penetration and NF-κB inhibition, was conjugated to PEGylated liposomes loaded with doxorubicin (CB5005-LS/DOX) or a fluorescent dye (CB5005-LS/dye). These CB5005-modified liposomes were utilized for targeting and penetrating glioma. Both qualitative and quantitative evaluations of CB5005-LS/dye showed that modification by CB5005 significantly increased cellular uptake of the liposomes by glioma cells, and substantially improved permeability of the liposomes into tumor spheroids. Intracellular localization studies demonstrated that CB5005-modified liposomes could not only penetrate into glioma cells but also deliver DOX into the nucleus. Cytotoxicity assay indicated that compared with the unmodified DOX liposomes (LS/DOX), CB5005-LS/DOX increased the efficiency of killing glioma cells by more than fivefold. In vivo imaging illustrated that CB5005-modified liposomes, via intravenous injection, distributed fluorescence into the brain and accumulated at tumor xenograft and intracranial glioblastoma in different animal models. More importantly, CB5005-LS/DOX treatment significantly prolonged the survival time of nude mice bearing intracranial glioblastoma. In summary, CB5005-modified liposomes represent a promising drug delivery system for cancer treatment attributing to its unique ability not only to transfer drugs to the tumor sites but also to function as a synergist for chemotherapy of glioma and other human tumors.

Functionalized cell nucleus-penetrating peptide combined with doxorubicin for synergistic treatment of glioma.

UNLABELLED: Clinical application of cell-penetrating peptides (CPPs) in cancer therapy is greatly restricted due to lack of tissue selectivity and tumor-targeting ability. CB5005, a rationally designed CPP that targets and inhibits intracellular NF-κB activation, is constituted by a unique membrane-permeable sequence (CB5005M) cascading to a NF-κB nuclear localization sequence (CB5005N). In vitro cellular evaluation confirmed that CB5005 was effectively taken up by brain capillary endothelial cell bEnd.3 and glioma cells U87. The intracellular localization analysis further demonstrated that CB5005 could not only penetrate into the cells but also enter into their nuclei. More interestingly, CB5005 permeated deeply into the tumor spheroids of U87 cell. In vivo imaging illustrated that the fluorescence-labeled CB5005 distributed itself into the brain and accumulated at the tumor site after intravenous injection. Given the important role of over expressed NF-κB in tumor growth and development, we further investigated CB5005 for its potential in treatment of glioma. When combined administration in vitro with doxorubicin (DOX), CB5005 exhibited a synergistic effect in killing U87 cells. In a nude mice xenograft model, CB5005 inhibited the growth of tumor when applied alone, and displayed a synergistic anti-tumor effect with DOX. In conclusion, CB5005 functioned simultaneously as a cell penetrating peptide and a tumor growth inhibitor, therefore can work as a potential synergist for chemotherapy of human tumor. STATEMENT OF SIGNIFICANCE: Clinical application of cell-penetrating peptides in cancer therapy is restricted due to lack of tissue selectivity and tumor-targeting ability. In this manuscript, we reported a rationally designed peptide, named CB5005, which had an attractive capability of translocation into the cell nucleus and blocking nuclear translocation of endogenous NF-κB protein. CB5005 had unique affinity with brain and glioma, and could rapidly accumulate in these tissues after intravenous injection. Furthermore, CB5005 showed a synergistic effect on inhibiting gliomas when administrated with doxorubicin. This is the first literature report on this multi-functionalized peptide, which can work as a potential synergist for chemotherapy of tumor. This work should be of general interest to scientists in the fields of biomaterials, biology, pharmacy, and oncology.