Supramolecular Drug Delivery Systems Based on Host‐Guest Interactions for Nucleic Acid Delivery

Abstract

In bio‐medical field, one of the most challenging hurdles connected with development of therapeutics is the efficient transport and delivery of drugs to the infected cells of human body. Supramolecular chemistry provides innovative designs for effective biological applications such as drug and gene delivery. In various applications of supramolecular chemistry, macrocyclic molecules such as calixarenes, cyclodextrins, cucurbiturils, and pillar arenes serve as ideal hosts that can bind guest molecules based on the electron density and size of their cavities. This review focuses on the recent advancements in major supramolecular systems such as calixarenes (CA), curcurbiturils (CB), cyclodextrins (CD) and pillar[n] arenes (PAs). Owing to their non‐covalent interactions and adaptive capability, these supramolecular‐based nucleic acid delivery systems provide customized treatment options in cancer therapy. These supramolecular carriers are distinct due to their capacity to functionalize and alter their structure in accordance with the required application. The use of such amphiphilic macromolecules as a carrier for gene transfection have been thoroughly investigated leading to advancements in therapeutic research. The aim of this review is to highlight and showcase the endeavours of utilising supramolecular systems in drug/nucleic acid delivery.

Overcoming barriers with non-covalent interactions: supramolecular recognition of adamantyl cucurbit[n]uril assemblies for medical applications

“…130 Nowadays CB[ n ]s have taken over the prominent spot of highly promising macrocyclic candidates for biological applications and drug delivery. 98,122,125,131–151 Moreover, CB[ n ] hosts have shown potential as supramolecular antidotes, neutralizing the effects of a poison though the encapsulation of a small toxic molecule. 147,152,153 The so-called chemical reasons for these new trends are the observations that CDs, when compared to CB[ n ]s, show generally lower selectivity and weaker binding affinities 52 ( K a are usually lower than 10 5 M −1 ).…”

Probing the dynamical interaction of the para-sulfonato-calix[4]arene with an antifungal protein

“…Classical all-atom molecular dynamics (MD) simulations were performed using the AM-BER18 package 54 . Penicillum antifugal protein "PAF " protein (PDB: 6HA4, 55 residues) was used as interacting partner with para-sulfonato-calix [4]arene (sclx 4 ). The protonation state of PAF titratable residues was determined via the H++ server 55 at the experimental pH of 6.0 35 .…”

“…Functionalizable ligands have attracted growing interest, mostly for their potential applications, spanning from chemistry 1,2 , pharmaceutical fields [3][4][5] to material science 6,7 . Interaction of proteins with smaller ligands is a hallmark in Biochemistry, and has recently been implied in the conception of high-resolution tunable protein assemblies, with an increasing number of X-ray structures reported in the PDB databank.…”

“…Subsequent "Bound State" simulations allow to assess coordination and free binding energy ∆G 0 bind between protein and ligand. B) Two main modes of approaches for para-sulfonato-calix- [4]-arene (sclx 4 , in colored sticks) towards PAF (in orange cartoon, PDB ID 6HA4) identified in our MD simulations. The two binding sites at the protein surface, Site 1 and Site 2, which are labeled in green and in red throughout this work, are shown together with all protein lysines indicated in colored sticks and labeled in black.…”