Crumpled Aluminum Hydroxide Nanostructures as a Microenvironment Dysregulation Agent for Cancer Treatment

Marat I. Lerner, Georgy Mikhaylov, Alexey A. Tsukanov, Aleksandr S. Lozhkomoev, Elazar Gutmanas, Irena Gotman, Andreja Bratovs, Vito Turk, Boris Turk, Sergey G. Psakhye, Olga Vasiljeva

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Owing to their unique physicochemical properties, nanomaterials have become a focus of multidisciplinary research efforts including investigations of their interactions with tumor cells and stromal compartment of tumor microenvironment (TME) toward the development of next-generation anticancer therapies. Here, we report that agglomerates of radially assembled Al hydroxide crumpled nanosheets exhibit anticancer activity due to their selective adsorption properties and positive charge. This effect was demonstrated in vitro by decreased proliferation and viability of tumor cells, and further confirmed in two murine cancer models. Moreover, Al hydroxide nanosheets almost completely inhibited the growth of murine melanoma in vivo in combination with a minimally effective dose of doxorubicin. Our direct molecular dynamics simulation demonstrated that Al hydroxide nanosheets can cause significant ion imbalance in the living cell perimembranous space through the selective adsorption of extracellular anionic species. This approach to TME dysregulation could lay the foundation for development of novel anticancer therapy strategies.

Original languageEnglish
Pages (from-to)5401-5410
Number of pages10
JournalNano Letters
Volume18
Issue number9
DOIs
Publication statusPublished - 12 Sep 2018
Externally publishedYes

Keywords

  • aluminum hydroxide
  • cancer treatment
  • Crumpled nanosheets
  • ion balance
  • molecular dynamics simulation
  • tumor microenvironment

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