Design of N-Methyl-d-Glucamine-Based Resorcin[4]arene Nanoparticles for Enhanced Apoptosis Effects

Abstract

The addition of specific chemical groups in a macrocycle structure influences its functional properties and, consequently, can provide new possibilities, among which are aggregation properties, water solubility, biocompatibility, stimuli response, biological activity, etc. Herein, we report synthesis of new resorcin[4]­arene with N-methyl-d-glucamine groups on the upper rim and n-decyl chains on the lower rim, an investigation of its self-assembly behavior in aqueous media, and its use as a building block for the formation of drug nanocontainer. N-methyl-d-glucamine fragments in the resorcin[4]­arene structure promote higher stability in solutions, simplification of self-aggregation, and increased biological activity. Antimicrobial and hemolytic activity assessment revealed that this resorcin[4]­arene obtained is nontoxic. The study of cell penetration was carried out with both free and encapsulated doxorubicin (DOX). Surprisingly, DOX-loaded macrocycle aggregates are more efficient in causing apoptosis in human cancer cell line. Conceivably, this knowledge will help in the rational design of DOX combination for novel drug-administration strategies in cancer treatment.

Dynamic covalent macrocycles co-delivering genes and drugs against drug-resistant cancer

“…With the addition of DTT, the polymer was reduced to 1. These results demonstrated that, different from the most reported examples that have explored delivery systems using a specific known macrocycle, 21,40,41 the 1 was actually a reactant that produced the self-assembling macrocycles with the DOX during the slowly oxidative process. Thermodynamics directed the synthesis of the right self-assembling macrocycles that can efficiently encapsulate the DOX molecules, giving rise to a high DLC.…”

A Review of the Application of Resorcinarenes and SBA-15 in Drug Delivery

“…The synthesized compound showed antimicrobial activity only against Gram-positive bacteria. Evaluating its cytotoxic effect on human erythrocytes, it is found that this macrocycle does not cause complete hemolysis, unlike other derivatives of the calixarenes family [27].…”

Dual Brønsted acidic-basic function immobilized on the 3D mesoporous polycalix [4]resorcinarene: As a highly recyclable catalyst for the synthesis of spiro acenaphthylene/indene heterocycles

“…Calix [4]resorcinarene (C4RA) is one of the derivatives of C4A, made up of four resorcinol units connected by methylene bridges [ 56 , 57 ]. The substituent groups at the methylene bridges determine the conformers of C4RA, resulting in five stable isomers [ 56 , [58] , [59] , [60] , [61] , [62] ]. Modifying C4RA through various functional groups onto the eight hydroxyphenyl groups and aromatic rings provides a versatile platform for their multi-purpose use.…”