P‐Sulfocalix[6]arene as Nanocarrier for Controlled Delivery of Doxorubicin

Abstract

Given the high toxicity of the anthracycline antibiotic doxorubicin (DOX), it is relevant to search for nanocarriers that decrease the side effects of the drug and are able to transport it towards a therapeutic target Here, the encapsulation of DOX by p-sulfocalix[6]arene (calix) has been studied. The interaction of DOX with the macrocycle, as well as with DNA, has been investigated and the equilibrium constant for each binding process estimated. The results showed that the binding constant of DOX to DNA, K , is three orders of magnitude higher than that to calix, K . The ability of calixarenes to encapsulate DOX molecules, as well as the capability of the DOX molecules included into the inner cavity of the macrocycle to bind with DNA have been examined. Cytotoxicity measurements were done in different cancer and normal cell lines to probe the decrease in the toxicity of the encapsulated DOX. The low toxicity of calixarenes has also been demonstrated for different cell lines.

Chemotherapy Based on Supramolecular Chemistry: A Promising Strategy in Cancer Therapy

“…DOX exerts its cytotoxic effects through strong binding to the nitrogen base pairs of the polynucleotides leading to the inhibition of synthesis and transcription of polynucleotides. The inclusion complexation of DOX with p-sulfonatocalix[6]arene (SC6) was reported to reduce the side effects of DOX, increase its selectivity towards cancer cells and its potency [40]. This complexation was explained through electrostatic interaction between the negatively charged SC6 and the positively charged DOX at physiological pH (pH 7.4).…”

“…The SC4-DOX selectivity towards the cancerous cells was attributed to the flexible (non-rigid) structure of SC6, which allows for many conformations of the supramolecule, aiding in the approach of SC6 to the di-nucleic acid helix. This results in the interaction of the neutral side of SC6 (containing OH groups) with the polynucleotide of cancer cells enhancing the transport of DOX to the cancerous cells [40].…”

Metallo-Liposomes of Ruthenium Used as Promising Vectors of Genetic Material

“…Such vectors can be viral or non-viral, the latter being usually less harmful to the health of the patients [ 13 ]. The more utilized non-viral vectors are nanoparticles, micelles, calixarenes, cyclodextrins and liposomes [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ].…”

Role of Calixarene in Chemotherapy Delivery Strategies

“…This is an additional advantage that improves the localization at the site of action and the approach of the DOX when it is encapsulated. The interaction is facilitated by the high flexibility of calixarene which can assume different conformations and interact with the polynucleotide ( Table 1 ) [ 52 ].…”