Host-guest inclusion for enhancing anticancer activity of pemetrexed against lung carcinoma and decreasing cytotoxicity to normal cells

Chen, Junyi; Zhang, Yahan; Zhang, Yadan; Zhao, Liang; Chen, Longming; Chai, Yao; Meng, Zhao; Jia, Xueshun; Meng, Qingbin; Li, Chunju

doi:10.1016/j.cclet.2021.03.079

Cited by 21 publications

(9 citation statements)

References 49 publications

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“…As Figure c shows, 24 h after the treatment, DOX@G/WP6A showed significant improvement in the cytotoxicity of DOX against HepG-2 cells compared with free DOX. Multiple previous research studies have shown that the host–guest encapsulation using macrocyclic receptors could cut off the energy source from ATP hydrolysis to block the efflux pump. ,, The remarkable antitumor efficiency enhancement might be ascribed to the thorough release of DOX by a higher concentration ATP inside tumor cells and a synergistic competitive binding between WP6A and ATP. Conversely, DOX@G/WP6A exhibited much lower toxicity against the LO2 cell line than free DOX (Figure d), which might be due to the high stability of the assembled architectures and the normal ATP levels. , Furthermore, we confirmed that DOX@G/WP6A could effectively enhance the antitumor efficacy of DOX to HepG-2 cells and decrease the undesirable cytotoxicity against LO2 cells from the morphology of living cells (Figure S10).…”

Section: Resultsmentioning

confidence: 99%

“…All reagents and solvents were purchased commercially and used as received unless other specified (Supporting Information). WP6A was synthesized according to the method reported by our group previously …”

Section: Methodsmentioning

confidence: 99%

“…WP6A was synthesized according to the method reported by our group previously. 48 NMR Spectroscopy. Samples for 1:1 1 H NMR spectra were prepared in pD 7.4 deuterated phosphate buffer (10 mM).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…To quantitatively assess the association constant (K a ) of complex G/WP6A, a fluorescent indicator displacement assay was performed with eosin Y (EY) as the optimal reporter dye according to our reported result. 48 EY with high brightness was strongly engulfed into the cavity of WP6A (K a = 3.43 × 10 6 M −1 ), along with an effective complexation-induced fluorescence quenching. Upon gradual addition of G, the intrinsic emission of EY was regenerated by the displacement of EY/ WP6A (Figure 2a).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

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Supramolecular Drug Delivery System from Macrocycle-Based Self-Assembled Amphiphiles for Effective Tumor Therapy

Chen

Zhang²,

Zhao³

et al. 2021

ACS Appl. Mater. Interfaces

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Intelligent drug delivery systems (DDSs) that can improve therapeutic outcomes of antitumor agents and decrease their side effects are urgently needed to satisfy special requirements of treatment of malignant tumors in clinics. Here, the fabrication of supramolecular self-assembled amphiphiles based on the host−guest recognition between a cationic water-soluble pillar[6]arene (WP6A) host and a sodium decanesulfonate guest (G) is reported. The chemotherapeutic agent doxorubicin hydrochloride (DOX) can be encapsulated into the formed vesicle (G/WP6A) to construct supramolecular DDS (DOX@G/WP6A). WP6A affords strong affinities to G to avoid undesirable off-target leakage during delivery. Nanoscaled DOX@G/WP6A is capable of preferentially accumulating in tumor tissue via enhanced permeability and retention (EPR) effect. After internalization by tumor cells, the abundant adenosine triphosphate (ATP) binds competitively with WP6A to trigger the disintegration of self-assembled vesicles with the ensuing release of DOX. In vitro and in vivo research confirmed that DOX@G/WP6A is not only able to promote antitumor efficacy but also reduce DOX-related systemic toxicity. The above favorable findings are ascribed to the formation of ternary selfassembly, which profits from the combination of the factors of the EPR effect and the ATP-triggered release.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: ■ Experimental Sectionmentioning

confidence: 99%

Section: ■ Experimental Sectionmentioning

confidence: 99%

See 2 more Smart Citations

Supramolecular Drug Delivery System from Macrocycle-Based Self-Assembled Amphiphiles for Effective Tumor Therapy

Chen

Zhang²,

Zhao³

et al. 2021

ACS Appl. Mater. Interfaces

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“…Zeolitic imidazolate frameworks-8 (ZIF-8) is an important class of MOFs, which has great Molecules 2021, 26, 3878 2 of 7 potential in the construction of supramolecular drug delivery systems due to its stability in neutral, alkaline aqueous solutions and rapid decomposition in acidic solutions [15,16]. In addition, pillar[n]arenes, as a novel macrocyclic host molecule, can be used to construct nano-drug carriers through host-guest interaction [17,18], thus improving the solubility and stability of drugs [19][20][21]. Recently, based on the coordination between water-soluble carboxylated pillar [6]arene (WP6) and ZIF-8@DOX, we have developed a supramolecular targeted drug hybrid material with good dispersion efficiency, and host-guest complexation of WP6 and G as necessary modifiers to improve it0s water dispersion and give it target properties [22,23].…”

Section: Introductionmentioning

confidence: 99%

A Supramolecular Photosensitizer System Based on Nano-Cu/ZIF-8 Capped with Water-Soluble Pillar[6]arene and Methylene Blue Host–Guest Complexations

Chao

et al. 2021

Molecules

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Photodynamic therapy (PDT) as a safe, non-invasive modality for cancer therapy, in which the low oxygen and high glutathione in the tumor microenvironment reduces therapeutic efficiency. In order to overcome these problems, we prepared a supramolecular photosensitive system of O2-Cu/ZIF-8@ZIF-8@WP6–MB (OCZWM), which was loaded with oxygen to increase the oxygen concentration in the tumor microenvironment, and the Cu2+ in the system reacted with glutathione (GSH) to reduce the GSH concentration to generate Cu+. It is worth noting that the generated Cu+ can produce the Fenton reaction, thus realizing the combination therapy of PDT and chemodynamic therapy (CDT) to achieve the purpose of significantly improving the anti-cancer efficiency.

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Pillararene‐Based Stimuli‐Responsive Supramolecular Delivery Systems for Cancer Therapy

Li,

Shen,

Yang

et al. 2024

Advanced Materials

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Cancer poses a significant challenge to global public health, seriously threatening human health and life. Although various therapeutic strategies, such as chemotherapy (CT), radiotherapy, phototherapy, and starvation therapy, have been applied to cancer treatment, their limited therapeutic effect, severe side effects, and unsatisfactory drug release behavior need to be carefully considered. Thus, there is an urgent need to develop efficient drug delivery strategies for improving cancer treatment efficacy and realizing on‐demand drug delivery. Notably, pillararenes, as an emerging class of supramolecular macrocycles, possess unique properties of highly tunable structures, superior host–guest chemistry, facile modification, and good biocompatibility, which have been widely used in cancer therapy to achieve controllable drug release and reduce the toxic side effects on normal tissues under various internal/external stimuli conditions. This review summarizes the recent advance of stimuli‐responsive supramolecular delivery systems (SDSs) based on pillararenes for tumor therapy from the perspectives of different assembly methods and hybrid materials, including molecular‐scale SDSs, supramolecular nano self‐assembly delivery systems, and nanohybrid SDSs. Moreover, the prospects and critical challenges of stimuli‐responsive SDSs based on pillararenes for cancer therapy are also discussed.This article is protected by copyright. All rights reserved

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Host-guest inclusion for enhancing anticancer activity of pemetrexed against lung carcinoma and decreasing cytotoxicity to normal cells

Cited by 21 publications

References 49 publications

Supramolecular Drug Delivery System from Macrocycle-Based Self-Assembled Amphiphiles for Effective Tumor Therapy

Supramolecular Drug Delivery System from Macrocycle-Based Self-Assembled Amphiphiles for Effective Tumor Therapy

A Supramolecular Photosensitizer System Based on Nano-Cu/ZIF-8 Capped with Water-Soluble Pillar[6]arene and Methylene Blue Host–Guest Complexations

Pillararene‐Based Stimuli‐Responsive Supramolecular Delivery Systems for Cancer Therapy

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