A Novel Peptide Enhances Therapeutic Efficacy of Liposomal Anti-Cancer Drugs in Mice Models of Human Lung Cancer

Abstract

Lung cancer is the leading cause of cancer-related mortality worldwide. The lack of tumor specificity remains a major drawback for effective chemotherapies and results in dose-limiting toxicities. However, a ligand-mediated drug delivery system should be able to render chemotherapy more specific to tumor cells and less toxic to normal tissues. In this study, we isolated a novel peptide ligand from a phage-displayed peptide library that bound to non-small cell lung cancer (NSCLC) cell lines. The targeting phage bound to several NSCLC cell lines but not to normal cells. Both the targeting phage and the synthetic peptide recognized the surgical specimens of NSCLC with a positive rate of 75% (27 of 36 specimens). In severe combined immunodeficiency (SCID) mice bearing NSCLC xenografts, the targeting phage specifically bound to tumor masses. The tumor homing ability of the targeting phage was inhibited by the cognate synthetic peptide, but not by a control or a WTY-mutated peptide. When the targeting peptide was coupled to liposomes carrying doxorubicin or vinorelbine, the therapeutic index of the chemotherapeutic agents and the survival rates of mice with human lung cancer xenografts markedly increased. Furthermore, the targeting liposomes increased drug accumulation in tumor tissues by 5.7-fold compared with free drugs and enhanced cancer cell apoptosis resulting from a higher concentration of bioavailable doxorubicin. The current study suggests that this tumor-specific peptide may be used to create chemotherapies specifically targeting tumor cells in the treatment of NSCLC and to design targeted gene transfer vectors or it may be used one in the diagnosis of this malignancy.

Liposome as nanocarrier: Site targeted delivery in lung cancer

“…Chang et al [88] deliberated the separation from a phage-exposing peptide library by the method of Zwick et al [89], a novel peptide ligand that attached to non-small lung cancer cell lines. The phage was ordained to a number of NSCLC cell lines excluding typical cells.…”

“…In severe combined immunodeficiency (SCID) mice containing (NSCLC) xenografts by Sandler et al [90], the targeting phage specially bounded to tumor grass roots. The targeting phage's tumor homing ability by the analogous synthetic peptide was repressed [88]. Chang et al [88] concluded that when the targeted peptide fixed with DOX or vinorelbine with liposomes, the counteractive manifestation of the chemotherapeutic entities and the resilience rates of mice elevated with human lung cancer xenografts.…”

“…Chang et al [88] concluded that when the targeted peptide fixed with DOX or vinorelbine with liposomes, the counteractive manifestation of the chemotherapeutic entities and the resilience rates of mice elevated with human lung cancer xenografts. Liposomes augmented drug count in tumor cells 5.7 times compared to free drugs and boosted cancer cell death caused by a bioavailable DOX high level [88].…”

“…Chang et al [96] studied the targeted working of ligand-mediated drug liberation system with a peptide, SP5-2 that is an imitated peptide, which predominantly attached to (NSCLC) cells [97]. Liposomal conjugation of SP5-2 improved the magnitude of drug directly added into NSCLC cells via receptor-controlled endocytosis.…”

Combined Delivery and Magnetic Resonance Imaging of Neural Cell Adhesion Molecule–Targeted Doxorubicin-Containing Liposomes in Experimentally Induced Kaposi's Sarcoma

“…To this purpose, liposomes have been functionalized with specific ligands (peptides, monoclonal antibodies, and small organic molecules) able to bind and to internalize receptors expressed on tumor vasculature or on tumor cells (19)(20)(21)(22)(23)(24).…”