Layered Double Hydroxide-Based Micro "Chemical Factory" with Arsenic Processing and Screening Functions on Nitinol for Gallbladder Cancer Treatment

Small. 2022 Sep;18(39):e2202908. doi: 10.1002/smll.202202908. Epub 2022 Aug 25.

Abstract

Gallbladder cancer is a common malignant tumor of the biliary system with a high fatality rate. Nitinol (Ni-Ti) stents, a standard treatment for prolonging patients' lives, are susceptible to reocclusion and cannot inhibit tumor recurrence because they lack antitumor and antibacterial activity. Herein, an arsenic-loaded layered double-hydroxide film is constructed on Ni-Ti, forming a micro "chemical factory." The LDH plays the role of a "processer" which absorbs highly toxic trivalent arsenic (As(III)) and processes it into lowly toxic pentavalent arsenic (As(V)). It also acts as a "quality-inspector," confining As(III) in the interlayer and releasing only As(V) (the finished product) to the outside. This control mechanism minimizes the toxicity during contact with normal tissue. The acidic microenvironment and overexpression of glutathione in tumor tissues not only accelerates the release of arsenic from the platform but also triggers the in situ transformation of arsenic from lowly toxic As(V) to highly toxic As(III), exerting a strong arsenic-mediated antineoplastic effect. Such a microenvironment-responsive "chemical factory" with arsenic processing and screening functions is expected to prevent tumor overgrowth, metastasis, and bacterial infection and provide new insights into the design of Ni-Ti drug-eluting stents for gallbladder cancer treatment.

Keywords: arsenic; gallbladder cancer; layered double hydroxides; nitinol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alloys
  • Anti-Bacterial Agents / pharmacology
  • Arsenic*
  • Early Detection of Cancer
  • Gallbladder Neoplasms* / drug therapy
  • Glutathione
  • Humans
  • Hydroxides
  • Nickel
  • Titanium
  • Tumor Microenvironment

Substances

  • Alloys
  • Anti-Bacterial Agents
  • Hydroxides
  • titanium nickelide
  • nitinol
  • Nickel
  • hydroxide ion
  • Titanium
  • Glutathione
  • Arsenic