Xiao-yu Hu

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Organization: Nanjing University

Department: School of Materials Science and Engineering

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Organic Chemistry

Rotaxane

Chemicals
References

Dual-Responsive Bola-Type Supra-Amphiphile Constructed from Water-Soluble Pillar[5]arene and Naphthalimide-Containing Amphiphile for Intracellular Drug Delivery

Co-reporter:Xin Liu, Keke Jia, Yichen Wang, Wei Shao, Chenhao Yao, Luming Peng, Dongmei Zhang, Xiao-Yu HuLeyong Wang

ACS Applied Materials & Interfaces 2017 Volume 9(Issue 5) pp:

Publication Date(Web):January 18, 2017

DOI:10.1021/acsami.7b00643

Supramolecular construction of multistimuli platform for drug delivery is a challenging task. In this work, a pH and GSH (glutathione) dual-responsive bola-type supramolecular amphiphile was successfully fabricated by the complexation between a water-soluble pillar[5]arene (WP5) and a bolaform naphthalimide guest (G) in water. The resulting bola-type amphiphile further self-assembled into supramolecular binary vesicles, which could be disassembled by low pH, a high-GSH-concentration environment, or both. Furthermore, the results of drug loading and releasing tests showed that doxorubicin (DOX), the hydrophobic anticancer drug, could be successfully encapsulated into the Stern region of the obtained supramolecular vesicles and generated the DOX-loaded vesicles with good drug-loading efficiency. Moreover, the obtained DOX-loaded vesicles displayed efficient and rapid DOX release at a simulated tumor microenvironment with low-pH or excess-GSH conditions or both. Significantly, cytotoxicity experiments revealed that the DOX-loaded supramolecular vesicles could obviously improve the anticancer efficiency of free DOX for tumor cells while remarkably reducing its side effects for normal cells. In vitro cellular uptake and subcellular localization assays further proved that these smart drug nanovehicles, entering cancer cells mainly via endocytosis, could cause excellent drug accumulation in cancer cells. The present study provides a successful example with which to rational design an effective bola-type stimuli-responsive supramolecular nanocarrier, which might have wide potential applications in the construction of various controlled drug-delivery systems.Keywords: drug delivery; dual-responsiveness; pillar[5]arene; self-assembly; supra-amphiphile;

GSH-Responsive supramolecular nanoparticles constructed by β-D-galactose-modified pillar[5]arene and camptothecin prodrug for targeted anticancer drug delivery

Co-reporter:Xin Liu;Wei Shao;Yanjing Zheng;Chenhao Yao;Luming Peng;Dongmei Zhang;Leyong Wang

Chemical Communications 2017 vol. 53(Issue 61) pp:8596-8599

Publication Date(Web):2017/07/27

DOI:10.1039/C7CC04932C

Supramolecular construction of a targeted and stimuli-responsive drug delivery system is still a challenging task. Herein, GSH-responsive supramolecular prodrug nanoparticles were constructed by the host–guest complexation between a β-D-galactose-functionalized water-soluble pillar[5]arene (GalP5) and a disulfide bond containing camptothecin prodrug (G). The obtained prodrug nanoparticles were stable under physiological conditions, whereas efficient drug release was triggered in a simulated tumor environment with high GSH concentration. In vitro studies revealed that these prodrug nanoparticles preferentially entered asialoglycoprotein receptor-overexpressing HepG2 cells due to the active targeting effect of galactose units. This active targeting effect resulted in the maximization of anticancer efficacy and reduction of the undesirable side effects to normal cells.

Supramolecular polymersomes constructed from water-soluble pillar[5]arene and cationic poly(glutamamide)s and their applications in targeted anticancer drug delivery

Co-reporter:Shuwen Guo;Tingxizi Liang;Yongshang Song;Ming Cheng;Jun-Jie Zhu;Leyong Wang

Polymer Chemistry (2010-Present) 2017 vol. 8(Issue 37) pp:5718-5725

Publication Date(Web):2017/09/26

DOI:10.1039/C7PY01259D

The development of smart and targeted drug delivery systems has promising potential to revolutionize cancer chemotherapy. Herein, supramolecular polymersomes were constructed using biocompatible water-soluble pillar[5]arene (WP5) and cationic poly(glutamamide)s (polymer 1) with good biodegradability. Based on the host–guest complexation between WP5 and butyl-ammonium groups on polymer 1, stable supramolecular macromolecular amphiphiles were obtained, which could self-assemble into supramolecular polymersomes. Furthermore, the generated polymersomes were able to encapsulate the hydrophilic anticancer drug mitoxantrone (MTZ) to achieve MTZ-loaded polymersomes. Importantly, decorated with biotin ligands on the surface, these polymersomes exhibited good targeting ability to deliver MTZ specifically to biotin receptor-positive cancer cells. After internalization into cancer cells, the loaded MTZ was released efficiently triggered by the acidic environment-induced polymersome disassembly. Moreover, MTZ-loaded polymersomes with targeting ligands on their surface could not only enhance the anticancer efficiency of MTZ but also effectively reduce the undesirable side effects on normal cells. The present work provides a novel strategy for the construction of smart supramolecular polymersomes, which may hold potential biomedical applications in targeted drug delivery.

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

Co-reporter:Xuan Wu;Lei Gao;Leyong Wang

The Chemical Record 2016 Volume 16( Issue 3) pp:1216-1227

Publication Date(Web):

DOI:10.1002/tcr.201500265

Supramolecular Nanoparticles Constructed by DOX-Based Prodrug with Water-Soluble Pillar[6]arene for Self-Catalyzed Rapid Drug Release

Co-reporter:Yu Cao, Yan Li, Xiao-Yu Hu, Xiaochun Zou, Shuhan Xiong, Chen Lin, and Leyong Wang

Chemistry of Materials 2015 Volume 27(Issue 3) pp:1110

Publication Date(Web):January 14, 2015

DOI:10.1021/cm504445r

The constructing of novel supramolecular prodrug nanoparticles based on the host–guest interaction of water-soluble pillar[6]arene (WP6) and novel doxorubicin (DOX)-based prodrugs (G1 or G2) is reported, in which these two kinds of prodrugs are synthesized by conjugating DOX with a flexible alkyl chain or a short EGn chain via an acid-cleavable hydrazone bond. The obtained supramolecular nanoparticles are stable under physiological conditions, whereas the cumulative release of DOX is approximate to 100% within 30 min at pH 5.5 by simulating the endolysosomal environment at 37 °C. It is noteworthy that WP6 can efficiently catalyze the cleavage of hydrazone bond of the prodrug G1 or G2 via a favored intramolecular process under acidic conditions. Moreover, intracellular localization experiments demonstrated that these two nanoparticles, taken up by cancer cells via endocytosis, can lead to efficient DOX accumulation in SKOV3 cancer cells. Cytotoxicity experiments further suggest that these nanoparticles can efficiently inhibit the proliferation of cancer cells and exhibit potent antitumor activity.

pH-Responsive supramolecular vesicles assembled by water-soluble pillar[5]arene and a BODIPY photosensitizer for chemo-photodynamic dual therapy

Co-reporter:Lu-Bo Meng, Wenyi Zhang, Dongqi Li, Yan Li, Xiao-Yu Hu, Leyong Wang and Guigen Li

Chemical Communications 2015 vol. 51(Issue 76) pp:14381-14384

Publication Date(Web):04 Aug 2015

DOI:10.1039/C5CC05785J

Supramolecular vesicles which can successfully encapsulate DOX and exhibit rapid drug release in a low-pH environment are constructed based on the host–guest interaction of water-soluble pillar[5]arene and a BODIPY derivative. They show remarkable combination of chemo- and photodynamic activities, suggesting a promising drug nanocarrier.

Cover Picture: Supramolecular Prodrug Micelles Constructed by Drug-Drug Conjugate with Water Soluble Pillar[6]arene for Controllable and Rapid Drug Release (Chin. J. Chem. 3/2015)

Co-reporter:Yu Cao;Xiaochun Zou;Shuhan Xiong;Yan Li;Yingzhong Shen;Xiaoyu Hu;Leyong Wang

Chinese Journal of Chemistry 2015 Volume 33( Issue 3) pp:

Publication Date(Web):

DOI:10.1002/cjoc.201590006

Controllable Fabrication of Various Supramolecular Nanostructures Based on Nonamphiphilic Azobenzene Derivatives and Pillar[6]arene

Co-reporter:Shan Qin;Shuhan Xiong;Yang Han;Leyong Wang

Chinese Journal of Chemistry 2015 Volume 33( Issue 1) pp:107-111

Publication Date(Web):

DOI:10.1002/cjoc.201400508

Abstract

Various novel types of supramolecular nanostructures formed by nonamphiphilic azobenzene derivatives, G1 or G2 have been successfully fabricated, where G2 is structurally similar with G1 but an extra phenoxy group is connected with the azobenzene motif . Micellar structures can be obtained from the self-assembly of G1, which further transform to large-sized spindle structures; while nanorods can be initially formed by G2, which will gradually aggregate to form layered structures with much larger size. Moreover, it is found that upon addition of WP6, which can form inclusion-complex with G1 or G2, separately, the nonamphiphilic G1 and G2 thus converse to supramolecular amphiphiles WP6⊃G1 and WP6⊃G2, respectively. Consequently, both of the above WP6⊃G1 and WP6⊃G2 complexes can further assemble to form supramolecular binary vesicles, which will gradually transform to nanotubes (WP6⊃G1) or well-ordered nanosheets (WP6⊃G2).

Supramolecular Prodrug Micelles Constructed by Drug-Drug Conjugate with Water Soluble Pillar[6]arene for Controllable and Rapid Drug Release

Co-reporter:Yu Cao;Xiaochun Zou;Shuhan Xiong;Yan Li;Yingzhong Shen;Xiaoyu Hu;Leyong Wang

Chinese Journal of Chemistry 2015 Volume 33( Issue 3) pp:329-334

Publication Date(Web):

DOI:10.1002/cjoc.201400844

Abstract

The first attempt of constructing supramolecular prodrug micelles based on the host-guest interaction between water-soluble pillar[6]arene (WP6) and a novel doxorubicin (DOX)-based drug-drug conjugate (G) is reported, in which the drug-drug conjugate is synthesized by conjugating anticancer drug DOX with another drug isoniazide via the acid-cleavable hydrazone bond. The obtained WP6⊃G micelles are stable under physiological conditions, whereas the cumulative release of DOX is approximate to 100% within 30 min at pH 5.5 by simulating the endo-lysosomal environment at 37°C. Therefore, this WP6-based prodrug micelles can achieve efficient DOX accumulation in the acidic tumor cells within a short period of time, which is very important and valuable; meanwhile it can also reduce the unexpected premature burst release under physiological condition. Furthermore, cellular internalization and localization experiments demonstrated that these prodrug micelles enter cancer cells mainly via endocytosis and can lead to significant drug accumulation in SKOV3 cancer cells, implying its promising future for cancer therapy.

Controllable aggregation-induced emission based on a tetraphenylethylene-functionalized pillar[5]arene via host–guest recognition

Co-reporter:Jie Wu, Shu Sun, Xiaoqing Feng, Jianbing Shi, Xiao-Yu Hu and Leyong Wang

Chemical Communications 2014 vol. 50(Issue 65) pp:9122-9125

Publication Date(Web):17 Jun 2014

DOI:10.1039/C4CC03127J

A novel TPE-functionalized pillar[5]arene (TPEP5) was successfully synthesized, and the motion of the TPE motif was restricted via pillararene-based host–guest recognition-mediated cross-linking, resulting in the efficient “turn-on” of fluorescence emission based on the AIE mechanism.

The self-complexation of mono-urea-functionalized pillar[5]arenes with abnormal urea behaviors

Co-reporter:Mengfei Ni, Xiao-Yu Hu, Juli Jiang and Leyong Wang

Chemical Communications 2014 vol. 50(Issue 11) pp:1317-1319

Publication Date(Web):08 Nov 2013

DOI:10.1039/C3CC47823H

Mono-urea-functionalized pillar[5]arenes were prepared which exhibited abnormal urea behaviors. They were shown to form pseudo[1]rotaxanes with poor anion binding abilities in solution and [c2]daisy chains with an abnormal urea motif in the solid state.

Dynamic self-inclusion behavior of pillar[5]arene-based pseudo[1]rotaxanes

Co-reporter:Yangfan Guan, Pingying Liu, Chao Deng, Mengfei Ni, Shuhan Xiong, Chen Lin, Xiao-Yu Hu, Jing Ma and Leyong Wang

Organic & Biomolecular Chemistry 2014 vol. 12(Issue 7) pp:1079-1089

Publication Date(Web):19 Nov 2013

DOI:10.1039/C3OB42044B

It was found that spontaneous isomerization takes place between three isomers of a pillar[5]arene (P5)-based pseudo[1]rotaxane. The isomerization process could be monitored by 1H NMR spectra in polar solvent and the geometric configurations of the three isomers were further evaluated by theoretical calculations. In the threaded forms, the alkyl side chain might be preorganized by intramolecular N–H⋯O bonds between the urea group of the side chain and the methoxy group of the P5 and further stabilized by multiple interactions, including H-bonding, C–H⋯π interactions, and the steric effect of the N-Boc moiety. These cooperative interactions greatly enhance the stability of the threaded form in polar solvent, and endow it with very special self-inclusion behavior.

Pillar[5]arene-based side-chain polypseudorotaxanes as an anion-responsive fluorescent sensor

Co-reporter:Shu Sun, Xiao-Yu Hu, Dongzhong Chen, Jianbing Shi, Yuping Dong, Chen Lin, Yi Pan and Leyong Wang

Polymer Chemistry 2013 vol. 4(Issue 7) pp:2224-2229

Publication Date(Web):06 Feb 2013

DOI:10.1039/C3PY00162H

A linear pillar[5]arene-modified conjugated polymer was synthesized, and novel side-chain polypseudorotaxanes were formed via the host–guest interactions between the pillar[5]arene unit and n-octylpyrazinium salt. Compared with the conjugated polymer which shows strong fluorescence, the polypseudorotaxanes show very weak fluorescence due to the efficient electron transfer from the conjugated backbone to the n-octylpyrazinium cation. Moreover, upon addition of chloride anion to the solution of the side-chain polypseudorotaxanes, a disassembly process occurred, leading to fluorescence recovery of the conjugated polymer. Therefore, the novel side-chain polypseudorotaxanes could serve as an efficient anion-responsive fluorescent sensor.

A pillar[5]arene-based side-chain pseudorotaxanes and polypseudorotaxanes as novel fluorescent sensors for the selective detection of halogen ions

Co-reporter:Shu Sun, Jian-Bing Shi, Yu-Ping Dong, Chen Lin, Xiao-Yu Hu, Le-Yong Wang

Chinese Chemical Letters 2013 Volume 24(Issue 11) pp:987-992

Publication Date(Web):November 2013

DOI:10.1016/j.cclet.2013.07.014

A pseudorotaxane and its polypseudorotaxanes formed between pillar[5]arene moieties and n-octylpyrazinium cations as novel fluorescent sensors for the selective detection of halogen ions were reported. A collapse of these pillar[5]arene-based pseudorotaxanes and polypseudorotaxanes occurred upon the addition of Cl−, Br−, and I− (tetrabutylammonium salts), respectively, leading to their fluorescence recovery. The fluorescence enhancement of the pseudorotaxane and the polypseudorotaxanes increases in the order of I− < Br− < Cl−, and the differences in fluorescence intensity could be easily distinguished by naked eyes under UV light illumination.A pseudorotaxane and its polypseudorotaxanes formed between pillar[5]arene moieties and n-octylpyrazinium cations as novel fluorescent sensors for the selective detection of halogen ions were reported. The fluorescence enhancement of the pseudorotaxanes and the polypseudorotaxanes increases in the order of I− < Br− < Cl−, and the differences in fluorescence intensity could be easily distinguished by naked eyes under UV light illumination.

Stable pillar[5]arene-based pseudo[1]rotaxanes formed in polar solution

Co-reporter:Xuan Wu, Lei Gao, Junzhao Sun, Xiao-Yu Hu, Leyong Wang

Chinese Chemical Letters (November 2016) Volume 27(Issue 11) pp:

Publication Date(Web):November 2016

DOI:10.1016/j.cclet.2016.05.004

Mono-alkyl-functionalized pillar[5]arenes P1, P2, and P3 were synthesized by click reaction, which exhibited different self-assembly behavior in polar solvent DMSO. Stable pseudo[1]rotaxane was formed by the self-complexation from P1 or P2, whereas, concentration-dependent pseudorotaxane structures were generated by P3 which bearing more flexible side chain. Interestingly, the obtained pseudo[1]rotaxanes exhibited a dynamic fast assembly process upon adding NaBF4, resulting in the formation of Na+-induced pseudorotaxanes.Mono-alkyl-functionalized pillar[5]arenes P1, P2, and P3 were synthesized by click reaction, which exhibited different self-assembly behavior in polar solvent DMSO. Stable pseudo[1]rotaxane was formed by the self-complexation from P1 or P2, whereas, concentration-dependent pseudorotaxane structures were generated by P3. Moreover, the obtained pseudo[1]rotaxanes exhibited a dynamic fast assembly process upon adding NaBF4, resulting in the formation of Na+-induced pseudorotaxanes.

A novel dynamic pseudo[1]rotaxane based on a mono-biotin-functionalized pillar[5]arene

Co-reporter:Xuan Wu, Mengfei Ni, Wei Xia, Xiao-Yu Hu and Leyong Wang

Inorganic Chemistry Frontiers 2015 - vol. 2(Issue 9) pp:NaN1017-1017

Publication Date(Web):2015/06/19

DOI:10.1039/C5QO00159E

A mono-biotin-functionalized pillar[5]arene P1 was synthesized by the click reaction, which could form a stable pseudo[1]rotaxane P1′ in a non-polar or weak-polar solution. Interestingly, the obtained pseudo[1]rotaxane P1′ exhibited a dynamic slow disassembly process within the NMR timescale upon adding a strong-polar solvent or competitive guest. Moreover, this dynamic behavior also had potential application in aqueous solution, which might be used as a switch to turn on or off the bioactivity of the biotin moiety.

pH-Responsive supramolecular vesicles assembled by water-soluble pillar[5]arene and a BODIPY photosensitizer for chemo-photodynamic dual therapy

Co-reporter:Lu-Bo Meng, Wenyi Zhang, Dongqi Li, Yan Li, Xiao-Yu Hu, Leyong Wang and Guigen Li

Chemical Communications 2015 - vol. 51(Issue 76) pp:NaN14384-14384

Publication Date(Web):2015/08/04

DOI:10.1039/C5CC05785J

Dynamic self-inclusion behavior of pillar[5]arene-based pseudo[1]rotaxanes

Co-reporter:Yangfan Guan, Pingying Liu, Chao Deng, Mengfei Ni, Shuhan Xiong, Chen Lin, Xiao-Yu Hu, Jing Ma and Leyong Wang

Organic & Biomolecular Chemistry 2014 - vol. 12(Issue 7) pp:NaN1089-1089

Publication Date(Web):2013/11/19

DOI:10.1039/C3OB42044B

The self-complexation of mono-urea-functionalized pillar[5]arenes with abnormal urea behaviors

Co-reporter:Mengfei Ni, Xiao-Yu Hu, Juli Jiang and Leyong Wang