Cancer Cell Specific Delivery of Photosystem I Through Integrin Targeted Liposome Shows Significant Anticancer Activity

Many anticancer drugs are developed for the treatment of cancer from natural sources. Photosystem I (PSI), a protein complex present in the chloroplast, is involved in photosynthesis and generates reactive oxygen species (ROS) in plant. Here, we used the ROS generation property of PSI for cancer therapy. We show that PSI can enter into different kinds of cancer cell like human lung carcinoma (A549) and mouse melanoma (B16F10) cell lines and generate ROS inside the cells. It inhibits the proliferation of cancer cell and causes apoptotic death of cancer cells. We also show that PSI induces apoptosis through mitochondria-dependent internal pathway, induces caspase3, causes DNA fragmentation, and arrests cell cycle at SubG0 phase. We also prepared, using C<sub>16</sub>-LDV lipopeptide [C16 long chain attached on the N-terminal of the tripeptide containing amino acids leucine (L), aspartic acid (D), and valine (V) abbreviated as NH<sub>2</sub>-LDV-COOH], α<sub>4</sub>β<sub>1</sub> integrin targeted liposomal formulation of PSI, which specifically kills the cancer cell without affecting normal cells, and it is found to be more potent compared to clinically used drug doxorubicin. Finally, we found that LDV liposomal formulation of PSI inhibits the growth of tumor in C57BL/6J mice model.