Photo‐Controlled Reversible Microtubule Assembly Mediated by Paclitaxel‐Modified Cyclodextrin

Abstract

The design and construction of multi-stimuli-responsive supramolecular nanoassemblies that can mimic and regulate the fundamental biological processes have become a focus of interest in supramolecular chemistry. In this work, a perfect combination has been achieved between naturally occurring microtubules and artificially macrocyclic receptors. The self-assembling morphology of microtubules can be photo-tuned by the host-guest interaction of paclitaxel-modified β-cyclodextrin (PTX-CD) and photochromic arylazopyrazole (PTX-AAP). Moreover, the supramolecularly aggregated microtubules in a cellular environment can induce a pronounced cell morphological change and cell death. This supramolecular approach based on the secondary PTX-AAP⊂PTX-CD complexation provides us a facile method to reversibly control the intertubular aggregation behaviors of microtubules, which may bring new perspectives in the treatment of diseases related to improper protein aggregation.

NIR‐Light‐Activated Combination Therapy with a Precise Ratio of Photosensitizer and Prodrug Using a Host–Guest Strategy

“…On account of their intrinsic cavity and easy functionalization, macrocycles, including crown ethers, cyclodextrins (CDs), cucurbiturils, calixarenes, and pillararenes, have been widely employed as drug carriers, encapsulating chemotherapeutic drugs as guests. Through the formation of supramolecular complexes, the solubility of the drugs is enhanced, leading to a longer circulation time and a better therapeutic performance.…”

“…There are three popular strategies employed for the codelivery of PSs with prodrugs:i )the covalent conjugation of aPStoaprodrug, [24] ii)grafting the PS or drug with acarrier, and loading the other component as the cargo, [32] iii)coloading the two components within acarrier,such as polymers and inorganic porous nanoparticles. [33][34][35][36] Each of these strategies has its own disadvantages.T he main challenge is the difficulty in fine-tuning the ratio between PS and drug, because the ratio is largely related to chemical structure, functionalities,a nd performance.F or the fabrication of covalently conjugated prodrugs,t here are some drawbacks including complicated organic synthesis and purification process.F or the other two strategies,a chieving ap recise ratio between the two components is also difficult due to potential premature leakage during the preparation and transportation processes.The uncertainty arising from imprecise loading of therapeutic components may lead to alow or unpredictable therapeutic efficacy of the cancer treatment.On account of their intrinsic cavity and easy functionalization, macrocycles,i ncluding crown ethers, [37] cyclodextrins (CDs), [38][39][40] cucurbiturils, [41,42] calixarenes, [43] and pillararenes, [44] have been widely employed as drug carriers,e ncapsulating chemotherapeutic drugs as guests.T hrough the formation of supramolecular complexes,t he solubility of the drugs is enhanced, leading to al onger circulation time and [*] Dr.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.…”

“…On account of their intrinsic cavity and easy functionalization, macrocycles,i ncluding crown ethers, [37] cyclodextrins (CDs), [38][39][40] cucurbiturils, [41,42] calixarenes, [43] and pillararenes, [44] have been widely employed as drug carriers,e ncapsulating chemotherapeutic drugs as guests.T hrough the formation of supramolecular complexes,t he solubility of the drugs is enhanced, leading to al onger circulation time and ab etter therapeutic performance.C Ds are the most extensively investigated macrocycles in the pharmaceutical field for clinical usage. [45] Herein, we developed as upramolecular system with an optimized loading ratio of the PS and prodrug (Scheme 1).…”

NIR‐Light‐Activated Combination Therapy with a Precise Ratio of Photosensitizer and Prodrug Using a Host–Guest Strategy

“…On account of their intrinsic cavity and easy functionalization, macrocycles, including crown ethers, cyclodextrins (CDs), cucurbiturils, calixarenes, and pillararenes, have been widely employed as drug carriers, encapsulating chemotherapeutic drugs as guests. Through the formation of supramolecular complexes, the solubility of the drugs is enhanced, leading to a longer circulation time and a better therapeutic performance.…”

Cucurbit[8]uril Reactivation of an Inactivated Caspase‐8 Mutant Reveals Differentiated Enzymatic Substrate Processing

“…Supramolecular chemistry has recently emerged as a powerful tool for reversible control over protein function, dimerization, and assembly . Synthetic host–guest systems have shown relevant orthogonality to proteins.…”