Novel Approach to Generate a Self-Deliverable Ru(II)-Based Anticancer Agent in the Self-Reacting Confined Gel Space

Novina Malviya, Chanchal Sonkar, Rakesh Ganguly, Debojit Bhattacherjee, Krishna Pada Bhabak, Suman Mukhopadhyay

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Finding the most effective method for cancer treatment is one of the thought-provoking tasks. Drug delivery by collapsing of metallogel to the cancer cell is an appealing way out. Cancer cells have an acidic environment due to excessive accumulation of lactic acid. In this work, the novel G5 gelator with a strategically free carboxylic acid arm has been designed and fabricated and characterized by several spectroscopic and microscopic techniques. These experiments suggest the formation of an ordered supramolecular gel with clover-leaf-like morphology. Mechanical properties from rheological measurements suggest the viscoelastic nature of the gel. Furthermore, we have obtained crystals of G5 from the pure dimethyl sulfoxide solution, whereas gelation gets induced by addition of water. This G5 gelator loses its gelation capability once the carboxylate is esterified by layering with methanol, which furnished the crystals of Me-G5′ (G5′ = G5-H). Further, the G5 gelator is used for the formation of ruthenium metallogel. Interestingly, we obtained the monomeric species [Ru(G5′)(η6-p-cymene)Cl] [Ru(II)G5] only in confined gel space upon addition of a [Ru2(η6-p-cymene)2Cl4] dimer to G5. The Ru(II)G5 metallogel has an inherent anticancer property with an IC50 value of 10.53 μM for the A549 cancer cell line. Treatment of the Ru(II)G5 metallogel by lactic acid for mimicking the acidic environment of the malignant cell results in collapsing of the gel by releasing the ruthenium metal ion. This released ruthenium ion binds with the lactic acid derivative making the gelator G5 free and producing a new compound Ru(II)L, which has also shown the anticancer property. The molecular docking study revealed that the released G5 could interact with a monocarboxylate transporter to disrupt the lactate transport chain, which might induce apoptosis.
Original languageEnglish
Pages (from-to)47606-47618
Number of pages13
JournalACS Applied Materials and Interfaces
Volume11
Issue number50
Early online date22 Nov 2019
DOIs
Publication statusPublished - 18 Dec 2019
Externally publishedYes

Keywords

  • anticancer drug
  • drug delivery
  • ruthenium metallogel
  • self-assembly
  • trimesic acid

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