Supramolecular Vesicles Based on Amphiphilic Pillar[n]arenes for Smart Nano-Drug Delivery

Figures & data

Figure 1 (A) Synthetic route and chemical structure of P1; (B) self-assembly of P1 in water. Reprinted with permission from Yu GC, Ma YJ, Han CY, et al. A sugar-functionalized amphiphilic pillar[5]arene: synthesis, self-assembly in water, and application in bacterial cell agglutination. J Am Chem Soc. 2013;135:10310–10313.⁴⁸; Copyright 2013, American Chemical Society.

Figure 2 Chemical structures of WP5 and polymer 1, as well as schematic illustration of the redox-responsive self-assembly between WP5 and 1 in water.

Notes: Reprinted with permission from Chi XD, Yu GC, Ji XF, et al. Redox-responsive amphiphilic macromolecular [2] pseudorotaxane constructed from a water-soluble pillar[5]arene and a paraquat-containing homopolymer. ACS Macro Lett. 2015;4:996–999.⁵⁵; Copyright 2015, American Chemical Society.

Figure 3 Synthetic route to WP6.

Notes: Reprinted with permission from Yu GC, Xue M, Zhang ZB, et al. A water-soluble pillar[6]arene: synthesis, host−guest chemistry, and its application in dispersion of multiwalled carbon nanotubes in water. J Am Chem Soc. 2012;134:13248–13251.³⁸; Copyright 2012, American Chemical Society.

Figure 4 (A) Chemical structures and cartoon representations of WP5, and guest molecules G and GH2; (B) Cartoon representation of the self-assembly of GH2, (WP5)2⊃GH2, and the controlled behavior.

Notes: Reprinted with permission from Zhou YJ, Li ER, Zhao R, Jie KC. CO2-enhanced bola-type supramolecular amphiphile constructed from pillar[5]arene-based host−guest recognition. Org Lett. 2018;20:4888–4892.⁷⁷; Copyright 2018, American Chemical Society.

Figure 5 Synthetic route to phosphonated pillar[5]arene (PPA[5]).

Notes: Reprinted with permission from Huang X, Wu SS, Ke XK, Li XY, Du XZ. Phosphonated pillar[5]arene-valved mesoporous silica drug delivery systems. ACS Appl Mater Interfaces. 2017;9:19638–19645.³⁰; Copyright 2017, American Chemical Society.

Figure 6 (A) Charge reversal process of P5NH-DCA; (B) Binding to cancer cell membrane; (C) Disrupting cancer cell membrane; (D) Killing cancer cells.

Notes: Reprinted with permission from Chang YC, Chen JY, Yang JP, et al. Targeting the cell membrane by charge-reversal amphiphilic pillar[5]arene for the selective killing of cancer cells. ACS Appl Mater Interfaces. 2019;11:38497–38502.⁷⁹; Copyright 2019, American Chemical Society.

Figure 7 Chemical structures and cartoons of DSP5 and TPE-Q4 and the schematic presentation of their self-assembly into a fluorescent supramolecular system for the selective detection of Fe³⁺ ions.

Notes: Reprinted with permission from Wang X, Lou XY, Jin XY, Liang F, Yang YW. A binary supramolecular assembly with intense fluorescence emission, high pH stability, and cation selectivity: supramolecular assembly-induced emission materials. Research. 2019;2019:1454562.⁸¹; Copyright 2019, Science.

Figure 8 Synthetic route of tetra-alkylphosphine capped amphiphilic pillar[5]arene 1.

Notes: Reprinted with permission from Ogoshi T, Ueshima N, Yamagishi TA. An amphiphilic pillar[5]arene as efficient and substrate-selective phase-transfer catalyst. Org Lett. 2013;15:3742–3745.⁸²; Copyright 2019, American Chemical Society.

Figure 9 (A) Chemical structures and cartoon representations of 1, 2, and SDS and (B) Cartoon representation of gas-controlled self-assembly and dual-triggered release of calcein.

Notes: Reprinted with permission from Jie KC, Zhou YJ, Yao Y, Shi BB, Huang FH. CO₂-responsive pillar[5]arene-based molecular recognition in water: establishment and application in gas-controlled self-assembly and release. J Am Chem Soc. 2015;137:10472–10475.³⁷; Copyright 2015, American Chemical Society.

Figure 10 Schematic illustration of the formation of supramolecular vesicles and their pH-responsive drug release.

Notes: Reprinted with permission from Duan QP, Cao Y, Li Y, et al. pH-responsive supramolecular vesicles based on water-soluble pillar[6]arene and ferrocene derivative for drug delivery. J Am Chem Soc. 2013;135:10542–10549.⁶³; Copyright 2013, American Chemical Society.

Figure 11 Schematic illustration of the construction of supramolecular micelles (WP6⊃G1) or vesicles (WP6⊃G2) and the application of supramolecular vesicles in drug delivery.

Notes: Reprinted with permission from Hu XY, Jia KK, Cao Y, et al. Dual photo- and pH-responsive supramolecular nanocarriers based on water-soluble pillar[6]arene and different azobenzene derivatives for intracellular anticancer drug delivery. Chem Eur J. 2015;21:1208–1220.⁶⁴; © 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Figure 12 Schematic illustration of the glucose-responsive supramolecular insulin delivery system. (A) Chemical structure and the mechanism of multiresponsive diphenylboronic acid guest G. (B) Supramolecular self-assembly of the host–guest complex WP5⊃G into vesicles and their successful encapsulation of insulin and GOx as well as the efficient insulin release under hyperglycemic state.

Notes: Reprinted with permission from Zuo MZ, Qian WR, Xu ZQ, et al. Multiresponsive supramolecular theranostic nanoplatform based on pillar[5]arene and Diphenylboronic acid derivatives for integrated glucose sensing and insulin delivery. Small. 2018;14:e1801942.⁹¹; © 2018 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Figure 13 Chemical structures of G1, G2, and G3, as well as illustrations of the controlled drug release in response to the five stimuli.

Notes: Reprinted with permission from Jiang L, Huang X, Chen D, et al. Supramolecular vesicles coassembled from disulfide-linked benzimidazolium amphiphiles and carboxylate-substituted pillar-[6]arenes that are responsive to five stimuli. Angew Chem Int Ed. 2017;56:2655–2659.⁷³; © 2017 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Figure 14 Cartoon representation of constructing dual-target supramolecular vesicles and their properties in efficient drug delivery.

Notes: Reprinted with permission from Shang K, Wang Y, Lu YC, Pei ZC, Pei YX. Dual-targeted supramolecular vesicles based on the complex of galactose capped pillar[5]arene and triphenylphosphonium derivative for drug delivery. Isr J Chem. 2018;58:1205–1209.⁴⁹; © 2018 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Figure 15 Schematic illustration of the synthesis of CAAP5, the host-guest complexation with galactose derivatives (G), formation of vesicles (CAAP5G), and their GSH/pH dual-responsive drug release.

Notes: Reprinted with permission from Lu YC, Hou CX, Ren JL, et al. A multifunctional supramolecular vesicle based on complex of cystamine dihydrochloride capped pillar[5]arene and galactose derivative for targeted drug delivery. Int J Nanomed. 2019;14:3525–3532.⁹⁰; Copyright 2019, Dovepress.

Figure 16 Cartoon of the self-assembly and drug-loading process of a vesicle based on Trp-modified pillar[5]arene and a galactose derivative and its possible cellular pathways.

Notes: Reprinted with permission from Yang K, Chang YC, Wen J, et al. Supramolecular vesicles based on complex of Trp-modified pillar[5]arene and galactose derivative for synergistic and targeted drug delivery. Chem Mater. 2016;28:1990–1993.⁸⁹; Copyright 2016, American Chemical Society.

Figure 17 Schematic design of the drug–drug conjugate SVs for co-delivery of different anticancer drugs. Reprinted with permission from Shao W, Liu X, Sun GP, Hu XY, Zhu JJ, Wang LY. Construction of drug-drug conjugate supramolecular nanocarriers based on water-soluble pillar[6]arene for combination chemotherapy. Chem Commun. 2018;54:9462–9465.⁴³; Copyright 2018, Royal Society of Chemistry.

Figure 18 Construction of multifunctional supramolecular vesicles for combination cancer therapy.

Notes: Reprinted with permission from Wang Q, Tian L, Xu JZ, et al. Multifunctional supramolecular vesicles for combined photothermal/photodynamic/hypoxia-activated chemotherapy. Chem Commun. 2018;54:10328–10331.⁷⁴; Copyright 2018, Royal Society of Chemistry.

Scheme 1 Chemical structures of amphiphilic pillar[n]arenes.

Figure 19 Synthetic route of ferrocenium capped amphiphilic PA[5], Illustration of the formation of cationic vesicles, and their redox-responsive drug/siRNA release.

Notes: Reprinted with permission from Chang YC, Yang K, Wei P, et al. Cationic vesicles based on amphiphilic pillar[5]arene capped with ferrocenium: a redox-responsive system for drug/siRNA co-delivery. Angew Chem Int Ed. 2014;53:13126–13130.⁸⁸; © 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Yu GC, Ma YJ, Han CY, et al. A sugar-functionalized amphiphilic pillar[5]arene: synthesis, self-assembly in water, and application in bacterial cell agglutination. J Am Chem Soc. 2013;135:10310–10313. doi:10.1021/ja405237q23795751

 PubMed Web of Science ®Google Scholar

Chi XD, Yu GC, Ji XF, et al. Redox-responsive amphiphilic macromolecular [2] pseudorotaxane constructed from a water-soluble pillar[5]arene and a paraquat-containing homopolymer. ACS Macro Lett. 2015;4:996–999. doi:10.1021/acsmacrolett.5b00525

 PubMed Web of Science ®Google Scholar

Yu GC, Xue M, Zhang ZB, et al. A water-soluble pillar[6]arene: synthesis, host−guest chemistry, and its application in dispersion of multiwalled carbon nanotubes in water. J Am Chem Soc. 2012;134:13248–13251. doi:10.1021/ja306399f22827832

 PubMed Web of Science ®Google Scholar

Zhou YJ, Li ER, Zhao R, Jie KC. CO2-enhanced bola-type supramolecular amphiphile constructed from pillar[5]arene-based host−guest recognition. Org Lett. 2018;20:4888–4892. doi:10.1021/acs.orglett.8b0203330048143

 PubMed Web of Science ®Google Scholar

Huang X, Wu SS, Ke XK, Li XY, Du XZ. Phosphonated pillar[5]arene-valved mesoporous silica drug delivery systems. ACS Appl Mater Interfaces. 2017;9:19638–19645. doi:10.1021/acsami.7b0401528530792

 PubMed Web of Science ®Google Scholar

Chang YC, Chen JY, Yang JP, et al. Targeting the cell membrane by charge-reversal amphiphilic pillar[5]arene for the selective killing of cancer cells. ACS Appl Mater Interfaces. 2019;11:38497–38502. doi:10.1021/acsami.9b1349231556585

 PubMed Web of Science ®Google Scholar

Wang X, Lou XY, Jin XY, Liang F, Yang YW. A binary supramolecular assembly with intense fluorescence emission, high pH stability, and cation selectivity: supramolecular assembly-induced emission materials. Research. 2019;2019:1454562.

 PubMedGoogle Scholar

Ogoshi T, Ueshima N, Yamagishi TA. An amphiphilic pillar[5]arene as efficient and substrate-selective phase-transfer catalyst. Org Lett. 2013;15:3742–3745. doi:10.1021/ol401654623815706

 PubMed Web of Science ®Google Scholar

Jie KC, Zhou YJ, Yao Y, Shi BB, Huang FH. CO2-responsive pillar[5]arene-based molecular recognition in water: establishment and application in gas-controlled self-assembly and release. J Am Chem Soc. 2015;137:10472–10475. doi:10.1021/jacs.5b0596026248035

 PubMed Web of Science ®Google Scholar

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 PubMed Web of Science ®Google Scholar

Hu XY, Jia KK, Cao Y, et al. Dual photo- and pH-responsive supramolecular nanocarriers based on water-soluble pillar[6]arene and different azobenzene derivatives for intracellular anticancer drug delivery. Chem Eur J. 2015;21:1208–1220. doi:10.1002/chem.20140509525370941

 PubMed Web of Science ®Google Scholar

Zuo MZ, Qian WR, Xu ZQ, et al. Multiresponsive supramolecular theranostic nanoplatform based on pillar[5]arene and Diphenylboronic acid derivatives for integrated glucose sensing and insulin delivery. Small. 2018;14:e1801942. doi:10.1002/smll.20180194230073791

 PubMed Web of Science ®Google Scholar

Jiang L, Huang X, Chen D, et al. Supramolecular vesicles coassembled from disulfide-linked benzimidazolium amphiphiles and carboxylate-substituted pillar-[6]arenes that are responsive to five stimuli. Angew Chem Int Ed. 2017;56:2655–2659. doi:10.1002/anie.201611973

 PubMed Web of Science ®Google Scholar

Shang K, Wang Y, Lu YC, Pei ZC, Pei YX. Dual-targeted supramolecular vesicles based on the complex of galactose capped pillar[5]arene and triphenylphosphonium derivative for drug delivery. Isr J Chem. 2018;58:1205–1209. doi:10.1002/ijch.201800080

 Web of Science ®Google Scholar

Lu YC, Hou CX, Ren JL, et al. A multifunctional supramolecular vesicle based on complex of cystamine dihydrochloride capped pillar[5]arene and galactose derivative for targeted drug delivery. Int J Nanomed. 2019;14:3525–3532. doi:10.2147/IJN.S191256

 PubMed Web of Science ®Google Scholar

Yang K, Chang YC, Wen J, et al. Supramolecular vesicles based on complex of Trp-modified pillar[5]arene and galactose derivative for synergistic and targeted drug delivery. Chem Mater. 2016;28:1990–1993. doi:10.1021/acs.chemmater.6b00696

 Web of Science ®Google Scholar

Shao W, Liu X, Sun GP, Hu XY, Zhu JJ, Wang LY. Construction of drug-drug conjugate supramolecular nanocarriers based on water-soluble pillar[6]arene for combination chemotherapy. Chem Commun. 2018;54:9462–9465. doi:10.1039/C8CC05180A

 PubMed Web of Science ®Google Scholar

Wang Q, Tian L, Xu JZ, et al. Multifunctional supramolecular vesicles for combined photothermal/photodynamic/hypoxia-activated chemotherapy. Chem Commun. 2018;54:10328–10331. doi:10.1039/C8CC05560B

 PubMed Web of Science ®Google Scholar

Chang YC, Yang K, Wei P, et al. Cationic vesicles based on amphiphilic pillar[5]arene capped with ferrocenium: a redox-responsive system for drug/siRNA co-delivery. Angew Chem Int Ed. 2014;53:13126–13130. doi:10.1002/anie.201407272

 PubMed Web of Science ®Google Scholar