A mechanically interlocked molecular system programmed for the delivery of an anticancer drug

Barat, Romain; Legigan, Thibaut; Tranoy-Opalinski, Isabelle; Renoux, Brigitte; Péraudeau, Elodie; Clarhaut, Jonathan; Poinot, Pauline; Fernandes, Antony E.; Aucagne, Vincent; Leigh, David A.; Papot, Sébastien

doi:10.1039/c5sc00648a

Cited by 124 publications

(86 citation statements)

References 22 publications

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“…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.…”

Section: Methodsmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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

et al. 2019

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The co‐delivery of photosensitizers with prodrugs sensitive to reactive oxygen species (ROS) for light‐triggered ROS generation and cascaded prodrug activation has drawn tremendous attention. However, the absence of a feasible method to deliver the two components at a precise ratio has impaired the application potential. Herein, we report an efficient method to produce a nanosized platform for the delivery of an optimized ratio of the two components by the means of host–guest strategy for maximizing the combination therapy efficacy of cancer treatment. The key features of this host–guest strategy for the combination therapy are that the ratio between photosensitizer and ROS‐sensitive prodrug can be easily tuned, near‐infrared (NIR) irradiation can sensitize the photosensitizer and activate the paclitaxel prodrug for its release, and the accumulation process can be tracked by NIR imaging to maximize the efficacy of photodynamic and chemotherapy.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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

et al. 2019

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“…[4][5][6][7][8][9] Besides their extraordinary dynamic properties, the mechanical bond between macrocycle and thread in rotaxanes often results in a significant influence on their respective properties. 10 For instance, the macrocycle can serve as a noncovalently attached protecting group for the thread, [11][12][13][14][15][16] or modulate its photophysical properties. [17][18][19][20][21] These observations have motivated the search for mechanically interlocked materials beyond small-molecules, including metal organic frameworks, [22][23][24][25][26][27][28] and polymers.…”

Section: Introductionmentioning

confidence: 99%

The mechanical bond on carbon nanotubes: diameter-selective functionalization and effects on physical properties

Martínez‐Periñán

Juan

Pouillon³

et al. 2016

Nanoscale

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ABSTRACT:We describe the functionalization of SWNTs enriched in (6,5) chirality with electron donating macrocycles to yield rotaxane-type mechanically interlocked carbon nanotubes (MINTs). Investigations by means of TEM and control experiments corroborated the interlocked nature of the MINTs. A comprehensive characterization of the MINTs through UV-vis-NIR, Raman, fluorescence, transient absorption spectroscopy, cyclic voltammetry, and chronoamperometry was carried out. Analyses of the spectroscopic data reveal that the MINT-forming reaction proceeds with diameter selectivity, favoring functionalization of (6,5) SWNTs rather than larger (7,6) SWNTs. In the ground state, we found a lack of significant charge-transfer interactions between the electron donor exTTF and the SWNTs. Upon photoexcitation, efficient charge-transfer between the electron donating exTTF macrocycles and SWNTs was demonstrated. As a complement, we established significantly different charge-transfer rate constants and diffusion coefficients for MINTs and the supramolecular models, which confirms the fundamentally different type of interactions between exTTF and SWNTs in the presence or absence of the mechanical bond. Molecular mechanics and DFT calculations support the experimental findings.

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“…9 However, rare examples have been reported using host–guest recognition motifs to fabricate SBPs. Compared with other macrocyclic hosts, such as crown ethers, cyclodextrins, calixarenes, and cucurbiturils, 10 their unique symmetrical structure and easy modification endow pillar[ n ]arenes with superior properties in host–guest recognition, 11 which provide opportunities to construct smart stimuli-responsive SBPs.…”

Section: Introductionmentioning

confidence: 99%

Pillar[5]arene-based amphiphilic supramolecular brush copolymers: fabrication, controllable self-assembly and application in self-imaging targeted drug delivery

Zhao

et al. 2016

Polym. Chem.

125

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Supramolecular brush copolymers have attracted continuing interest due to their unusual architectures, fascinating properties, and potential applications in many fields involving smart stimuli-responsive drug delivery systems. Herein, the first pillararene-based amphiphilic supramolecular brush copolymer (P5-PEG-Biotin⊃PTPE) was constructed on the basis of the host–guest molecular recognition between a water-soluble pillar[5]arene (P5) and a viologen salt (M). P5-PEG-Biotin⊃PTPE self-assembled into supramolecular nanoparticles (SNPs), which were utilized as a self-imaging drug delivery vehicle by taking advantage of the aggregation-induced emission (AIE) effect. Encapsulation of anticancer drug doxorubicin (DOX) caused deactivation of the fluorescences of both the tetraphenylethene (TPE) and DOX chromophores due to the energy transfer relay (ETR) effect, mediated by Förster resonance energy transfer (FRET) and aggregation-caused quenching (ACQ). The release of loaded DOX molecules can be triggered by low pH and reductase, recovering the “silenced” fluorescence caused by the interruption of the ETR effect, achieving in situ visualization of the drug release process by observing the location and magnitude of the energy transfer-dependent fluorescence variation. The biotin ligands on the surfaces of the DOX-loaded SNPs act as targeting agents to deliver DOX preferentially to cancer cells over-expressing biotin receptor. In vitro studies demonstrated that the loading of DOX by this supramolecular nanomaterial exhibited selective cytotoxicity towards cancer cells over normal cells. The potency of this sophisticated supramolecular drug delivery system in cancer therapy was further evaluated in HeLa tumor-bearing mice. In vivo experiments confirmed that the DOX-loaded SNPs possess excellent antitumor efficacy with negligible systemic toxicity.

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A mechanically interlocked molecular system programmed for the delivery of an anticancer drug

Abstract: The development of mechanically interlocked molecular systems programmed to operate autonomously in biological environments is an emerging field of research with potential medicinal applications.

Cited by 124 publications

References 22 publications

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

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

The mechanical bond on carbon nanotubes: diameter-selective functionalization and effects on physical properties

Pillar[5]arene-based amphiphilic supramolecular brush copolymers: fabrication, controllable self-assembly and application in self-imaging targeted drug delivery

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