1. Academic Validation
  2. Engineering Alendronate-Composed Iron Nanochelator for Efficient Peritoneal Carcinomatosis Treatment

Engineering Alendronate-Composed Iron Nanochelator for Efficient Peritoneal Carcinomatosis Treatment

  • Adv Sci (Weinh). 2022 Sep 4;e2203031. doi: 10.1002/advs.202203031.
Jing Zhao 1 Xiuyu Huang 1 Peng Liu 1 Miaojuan Qiu 1 Binbin Li 1 Yingfei Wen 1 Yongshu Li 1 Qiang Wang 1 Meiying Wu 2 Yu Chen 3 Yihang Pan 1
Affiliations

Affiliations

  • 1 Precision Medicine Center, Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, P. R. China.
  • 2 School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, 518107, P. R. China.
  • 3 Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, P. R. China.
Abstract

Iron is an essential element for various cellular metabolism. Cancer cells also have high requirement of iron in their proliferation, invasion, and metastasis processes. Alendronate (ALN), a kind of FDA-approved bisphosphonates with metal-chelating capability, is initially certified to selectively bind to intracellular Fe3+ theoretically and experimentally in this study. Hence, CaALN iron nanochelator is rationally designed to kill Cancer cells by synergism of Fe-depletion and calcium accumulation. In vitro experiments and RNA sequencing analysis indicate that CaALN nanomedicine inhibits the proliferation of Cancer cells by depleting Fe, interfering with DNA replication, and triggering intracellular Reactive Oxygen Species (ROS). Meanwhile, released Ca2+ and ROS mutually promote and induce damage of cellular macromolecules, which leads to mitochondrial Apoptosis of Cancer cells. In an intraperitoneal disseminated mouse model with the human ovarian Cancer cells SKOV3, CaALN nanoparticles selectively accumulate in tumor tissues and result in significant retardation of tumor growth and ascites formation. The mean survival time of SKOV3-bearing mice in treatment group is prolonged from 33 to 90 d. These results indicate that the alendronate-originated iron chelator can serve as an efficient strategy for the treatment of peritoneal carcinomatosis.

Keywords

calcium overload; chemotherapy; infinite coordination polymers; iron chelator; ovarian cancer.

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