Lung cancer is a serious threat to human health with the highest morbidity and mortality; metastatic lung cancer accounts for a majority of cancer‐related deaths. Hence, there is considerable interest in developing efficient lung‐targeted drug delivery systems to improve overall survival and quality of life of lung cancer patients.
Based on the lung‐targeting characteristics of cubic crosslinked cyclodextrin metal–organic framework (CDF) nanoparticles, a study conducted by research team led by Prof. ZHANG Jiwen at Shanghai Institute of Materia Medica of Chinese Academy of Sciences shows the synthesis of a nanoplatform using RGD‐functionalized CDF to co‐deliver low‐molecular‐weight heparin (LMWH) and doxorubicin (DOX) for treatment of lung cancer. Rational design of the DOX‐loaded RGD‐CDF‐LMWH nanoplatform (RCLD) is carried out. RCLD nanoparticles are efficiently targeted to lung tumors following intravenous administration; RCLD accumulation in the lung is 5.8 times greater than that in the liver. Moreover, RCLD inhibits migration and invasion of cancer cells in vitro and significantly diminishes lung tumor nodule count and area of spread in human A549 and murine B16F10 lung cancer models in vivo. Furthermore, RCLD does not show serum enzyme or histopathologic indicators of tissue damage or adverse hematologic effects. Therefore, the multiple antitumor activities of this novel RCLD nanoplatform, alongside its safety profile for normal tissues, strongly support its use for targeted treatment of lung cancer.
△ Schematic of the RGD‐CDF‐LMWH‐DOX (RCLD) lung cancer targeted drug delivery system. A) Chemical structure of γ‐cyclodextrin (γ‐CD) and crosslinked CD‐MOF (CDF), and schematic diagram of RCLD. One unit of CDF is represented by the (γ‐CD)6 cube, while the (γ‐CD)6 units are connected to form 3D CDF nanocrystals. B) Schematic illustration of the role of RCLD in targeting lung cancer and inhibiting tumor cells.
The study was published in Advanced Functional Materials. PhD student HE Yaping at University of Chinese Academy of Sciences is the first author. The study was funded by the Strategic Priority Research Program of the Chinese Academy of Sciences, the Key Program for International Science and Technology Cooperation Projects of China, the National Science and Technology Major Projects for Major New Drugs Innovation and Development and the National Nature Science Foundation of China.
