Cancer is one of the top three fatal diseases in the world, and its treatment is still rudimentary despite tremendous advances made in chemotherapy and immunotherapy in the last decade. The frustrating limitations of chemotherapy are due to a number of factors, including random distribution of drugs in the body, ineffective concentration of drugs at the tumor site, poor drug permeability into the tumor cells, inadequate understanding of tumor microenvironment, and smart self-protection mechanisms evolved by the tumor cells. Numerous targeted drug delivery systems have been developed and tested in a hope to improvetherapeutic efficacy of existing drugs and new drug candidates. Unfortunately, the clinical efficacy of such targeted drug delivery systems has been unsatisfactory. Glioma is known to progress rapidly with poor prognosis. Glioma chemotherapy is especially challenging due to intrinsic obstacles of blood-brain barrier(BBB) and blood-brain tumor barrier(BBTB). Other critical factors to consider for successful treatment include understanding drug transport into glioma cells, and inhibiting anti-apoptosis and chemoresistance of the glioma cells. We attempt to integrate the above concerns into multi-functional liposomes by surface modification with a cell-permeable nuclear factor-κB(NF-κB) inhibitor, named CB5005, for treatment of glioma. CB5005 is a rationally designed peptide, which can be divided into two cascaded segments: a cell membranepermeable sequence and a nuclear localization sequence. The nuclear localization sequence of CB5005 is derived from p50 subunit of NF-κB, which can competitively prevent the translocation of activated NF-κB into nucleus. NF-κB is found to be constitutively activated in most malignant cells and in the tumor microenvironment. Thus, blocking NF-κB pathway can inhibit tumor growth and enhance the sensitivity of tumor cells to chemotherapeutic drugs. When applied with doxorubicin(DOX), CB5005 showed a synergistically antagonistic effect on glioma. Here, CB5005 was employed to modify PEGylated liposomes loaded with DOX for penetrating BBB and targeting glioma. Furthermore, CB5005-modified liposome delivery system is expected to improve the efficacy of those antineoplastic agents acting in the cell nuclei, and to be appropriate for those tumors associated with high NF-κB activity.