Supramolecular Drug Delivery Systems Based on Water-Soluble Pillar[n]arenes

Abstract

Supramolecular drug delivery systems (SDDSs), including various kinds of nanostructures that are assembled by reversible noncovalent interactions, have attracted considerable attention as ideal drug carriers owing to their fascinating ability to undergo dynamic switching of structure, morphology, and function in response to various external stimuli, which provides a flexible and robust platform for designing and developing functional and smart supramolecular nano-drug carriers. Pillar[n]arenes represent a new generation of macrocyclic hosts, which have unique structures and excellent properties in host-guest chemistry. This account describes recent progress in our group to develop pillararene-based stimuli-responsive supramolecular nanostructures constructed by reversible host-guest interactions for controllable anticancer drug delivery. The potential applications of these supramolecular drug carriers in cancer treatment and the fundamental questions facing SDDSs are also discussed.

Stimuli-Responsive Drug-Delivery Systems Based on Supramolecular Nanovalves

“…In this review, we summarize the recent supramolecular drug-delivery systems. 17 To date, drug therapeutics is still the most typical and dominant method in dealing with health problems, which has made great advances toward refractory diseases. However, two major challenges that drug therapeutics would encounter involve unfavorable invasions toward normal tissues caused by unspecific aggressivity and the difficulty in realizing sustained release within diseased cells.…”

Molecular Sensing with Host Systems for Hyperpolarized 129Xe

“…Acidic solution, counterions (e.g., Na + , K + ) also enhance solubility of CB[n]s CB[n]s Xe response can be regulated by changing the pH, temperature, counterions etc. Easily synthesizable and commercially available Larger CB[n]s might bind Xe in the presence of a co-guest that helps to probe supramolecular architecture CB[n]s forms oligomeric structures aimed for different applications CB[n]s form unconventional host-host inclusion complexes with different hosts e.g., cyclodextrin, calixarenes etc CB[7] exhibits relatively low developmental and organ-specific toxicity in zebrafish models albeit its biomedical application can be exploited at sub-toxic concentrations [ 240 ] CB[6] and CB[7] displayed no neurotoxicity at 1 mM concentration (1/3 of maximum tolerated dose for CB[7]) [ 241 ] CB[5] and CB[7] showed high cell tolerance at concentrations of up to 1 mM in cell lines originating from kidney, liver or blood tissue using cytotoxicity assays [ 242 ] CB[7] was efficiently internalized by macrophages indicating their potential for the intracellular delivery of drugs [ 242 ] Biochemical markers testing for vital organs of mice injected with CB[7] (5 g/kg orally, 500 mg/kg peritoneally and 150 mg/kg intravenously) showed excellent biocompatibility for CB[7] [ 243 ] Introduction of functionalizable handle onto CB[n]s structure is not straightforward and faces several synthetic hurdles ‘Even’ numbered CB[n]s are water insoluble or display meager solubility Presence of counterions reduces Xe association constant and its exchange rate Limited Xe chemical shift tunability since co-guest might be needed in certain cases to achieve the desired chemical shift change CB[n]s prefer linear alkylamines, hydrophobic guests over small hydrophobic Xe Multiplexing using CB[n] might be hindered by non-specific competitive binding of different guests. In vitro and in vivo translation are hampered for CB[n]s due to numerous non-specific binding endogenous competitive guests Exposing CB[7] to live zebrafish revealed measurable cardiotoxicity and locomotion and behavioral toxicity at concentrations of ca.…”

“…CB[5] and CB[7] showed high cell tolerance at concentrations of up to 1 mM in cell lines originating from kidney, liver or blood tissue using cytotoxicity assays [ 242 ]…”

“…CB[7] was efficiently internalized by macrophages indicating their potential for the intracellular delivery of drugs [ 242 ]…”

Preliminary investigation of novel tetra-tailed macrocycle amphiphile based nano-vesicles for amphotericin B improved oral pharmacokinetics

“…Such molecules include cyclophanes, catenanes, crown ethers, calixarenes, cucurbiturils, porphyrins, cryptophanes and carcerands [19][20][21]. Besides their drug protection, sustained release and targeting capabilities, supramolecular macrocycles owe good biocompatibility properties as well [22,23]. Though currently used nanocarriers are capable of improving drugs pharmacokinetics and reducing their adverse effects, yet elevated therapeutic benefits have not been achieved for the delivered drugs.…”