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.

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).

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.