4.8 Article

Pulmonary Targeting Crosslinked Cyclodextrin Metal-Organic Frameworks for Lung Cancer Therapy

期刊

ADVANCED FUNCTIONAL MATERIALS
卷 31, 期 3, 页码 -

出版社

WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.202004550

关键词

cancer therapy; cyclodextrin frameworks; low-molecular-weight heparin; lung-targeting carriers; RGD peptide

资金

  1. Strategic Priority Research Program of the Chinese Academy of Sciences [XDA12050307]
  2. Key Program for International Science and Technology Cooperation Projects of China [2020YFE0201700]
  3. National Science and Technology Major Projects for Major New Drugs Innovation and Development [2018ZX09721002-009]
  4. National Nature Science Foundation of China [81773645]

向作者/读者索取更多资源

The study synthesized RCLD nanoparticles with lung-targeting characteristics, which efficiently targeted lung tumors following intravenous administration, inhibited cancer cell migration and invasion, and reduced lung tumor count and spread area in vivo in lung cancer models. Furthermore, RCLD showed no signs of tissue damage or adverse hematologic effects, supporting its use for targeted treatment of lung cancer.
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, this study 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.

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