Immunoliposome delivery triptolide to lung cancer enhanced by Carbonic Anhydrase IX Antibody

Project: Research project

Project Details


Lung cancer is the most common cause of cancer-related death. According to the Hong Kong Cancer Registry, lung cancer accounted for 28% of all cancer deaths in the year of 2008, ranking with the highest mortality rate among all cancer types. The survival outcome in lung cancer patients has not been significantly improved.

Triptolide is a major active diterpenoid of herbal Tripterygium wilfordii Hook F, exhibited superior antitumor activity compared to gemcitabine as well as taxanes in vivo and in vitro. Cytotoxic synergy between triptolide and doxorubicin was observed in lung cancer cells, and triptolide also enhanced cell death by carboplatinum. Amazingly, triptolide alone or combined with TNF-a or chemotherapy, can induce apoptosis of tumor cell lines derived from human nonsmall lung carcinoma. However, the physical-biological properties, e.g. insolublility and strong toxicity to normal cells limit triptolid’s therapeutic potential; even though, a synthetic prodrug, minnelide, is being studied. Thus, it is desirable to seek strategy to facilitate triptolide targeting human nonsmall lung carcinoma.

Liposomes could offer important advantages such as good biocompatibility, low toxicity, and low immunogenicity. The goal of liposome-based drug delivery is to solubilize the insoluble ingredients, maximize therapeutic effects in tumor tissues and minimize toxic effects in normal tissues.

Immunoliposome has been developed by conjugating liposomes with whole or fragmented antibodies that can bind to specific cell surface antigens expressed by tumor cells. Although promising results have been obtained from recent studies of antibody-conjugated liposomes, the identification of the most useful antigen targets for delivery of anti-cancer agents to tumor cells is far from complete.

In this study, we are investigating the targeting capability of Carbonic Anhydrase IX(CA9), a cell surface antigen characterized by high expression in a variety of solid tumors and restricted expression in normal tissues. In the lung cancer, CA9 is readily present in malignant tumors, whereas all other normal lung specimens sampled at a distance from the tumor are negative. We are developing an immunoliposome by conjugating CA9 antibody as the drug carrier system targeting CA9, and integrate the technology of liposome with triptolid for lung cancer therapy. We will investigate the in vitro binding activity and cytotoxicity effect of this immunoliposome in human lung cancer cells. We will also investigate its biodistribution and therapeutic efficacy using a mouse lung cancer model. It is hoped that this study will ultimately bring us closer to the realization of targeted cancer therapy through the use of immunoliposomes.
Effective start/end date1/01/1531/12/16

UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being


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