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

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† ‡ †Organic & Medicinal Chemistry Division and ‡Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, West Bengal, India
*Fax: +91-33-2473-5197/0284. Phone: +91-33-2499-5872. E-mail: [email protected]
Cite this: ACS Appl. Mater. Interfaces 2017, 9, 1, 176–188
Publication Date (Web):December 6, 2016
https://doi.org/10.1021/acsami.6b13352
Copyright © 2016 American Chemical Society
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    Abstract

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    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 C16-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 NH2-LDV-COOH], α4β1 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.

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    This materials are available free of charge via the Internet at The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsami.6b13352.

    • Absorption and fluorescence spectra of PSI in water, cellular uptake study of PSI in A549, B16F10, and WI38 cells, effect of PSI on the cellular morphology of A549 cell with time, effect of PSI on the cell viability of WI38 normal cell, assay for evaluation of effect of PSI on microtubule network, BubR1 activation, Mad2 activation, ROS generation following DCF & DHE method in A549 cell, annexin V and propidium iodide assay in A549 cells after treatment with PSI, apoptosis study in B16F10 cells after treatment with PSI, study of cell cycle, tunnel assay in A549 and B16F10 cell after treatment with PSI, analytical HPLC chromatogram of the long-chain attached LDV lipopeptide, MALDI mass spectra of the LDV long-chain lipopeptide, DLS study to measure the size of LDV-liposome and LDV-liposome-PSI, cryo-electron microscopy of the LDV liposome-PSI, comparative cellular uptake of LDV-liposome-PSI and untagged-liposome-PSI into B16F10 cells in 2 & 4 h, cellular uptake of PSI in tumor spheroid, toxicity and immunohistochemistry study on C57BL/6J mice (PDF)

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