A novel approach with controlled nucleation and growth for green

Aug 28, 2018 - In this study, the nano and micro-sized cyclodextrin-based metal–organic frameworks (CD-MOFs) were successfully conducted using ...
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A novel approach with controlled nucleation and growth for green synthesis of size-controlled cyclodextrin-based metal -organic frameworks based on short-chain starch nanoparticles Chao Qiu, Jinpeng Wang, Huang Zhang, Yang Qin, Xueming Xu, and Zhengyu Jin J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.8b03144 • Publication Date (Web): 28 Aug 2018 Downloaded from http://pubs.acs.org on August 30, 2018

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Graphical Abstract

Add seeds

γ-CD

Resveratrol (Res) Nucleation

Res in water Res in ethanol Res loaded MOFs in water Res loaded MOFs in ethanol

1.0

Controlled growth

0.9

A0/A

0.8

Short amylose seeds

0.7 0.6 0.5 0.4 0.3

0

2

4

6

8

Time (h)

10

12

14

16

Stabilization of Res loaded MOFs

γ-CD-MOFs

Scheme 1. Schematic representation of the size-controlled synthesis of γ-CD-MOFs through facile and green seed-mediated method.

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A novel approach with controlled nucleation and growth for green

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synthesis of size-controlled cyclodextrin-based metal−organic

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frameworks based on short-chain starch nanoparticles

4

Chao Qiua,b,c, Jinpeng Wanga,b,c, Huang Zhanga,d, Yang Qina,b, Xueming Xua,b,c,

5

Zhengyu Jina,b,c,*

6 7

a. State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi,

8

Jiangsu 214122, China

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b. School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu

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214122, China

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c. Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University,

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Wuxi 214122, China

13

d. School of Food Engineering, Henan University of Animal Husbandry and Economy,

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Zhengzhou, Henan, 450046, China

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* Corresponding author:

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[email protected] (Z. Jin)).

Zhengyu

Jin (Tel:/Fax: 86-51085913299; Email:

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ABSTRACT: In this study, the nano and micro-sized cyclodextrin-based

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metal–organic

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short-chain starch nanoparticles as seeds through seed-mediated method. The

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morphology, size, crystal structure, thermal and N2 adsorption properties of

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CD-MOFs prepared at different time intervals were investigated. The scanning

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electron microscopy results showed that the size variation from nanometer to

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millimeter could be controlled by crystal growth time. The CD-MOFs based on

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short-chain starch nanoparticle had higher crystallinity and N2 uptake, thus indicating

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that the method of seed-mediated was more facile and efficient than the previous

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approach. Resveratrol (Res) is a natural polyphenol compound that has anticancer and

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antimicrobial activities against several pathogens. However, this compound suffers

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from poor stability. Trans-Res rapidly isomerizes when exposed under ultraviolet or

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visible light. The results showed that the stability of Res was substantially enhanced

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by its encapsulation in CD-MOF crystals.

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KEYWORDS: γ-cyclodextrin, resveratrol, seed-mediated method, cytotoxicity,

32

stability

frameworks

(CD-MOFs)

were

successfully

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using

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INTRODUCTION

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Metal–organic frameworks (MOFs) as porous crystalline solid materials have

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attracted increasing interest because of their diverse potential applications, including

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gas adsorption,1-3 separation,4 molecular recognition,5,6 and drug delivery carrier.7-10

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MOFs were composed of metal ions and multitopic organic ligands bridged by

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coordination bonds. Compared with conventional material, MOFs have distinct

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advantages, such as a large surface area, tunable size and ultra-high porosity.11

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However, MOFs based on non-food grade organic linkers and transition metals

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considered to be toxic are not acceptable for food and biomedical applications.7,12

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Cyclodextrins (CDs) are a kind of natural cyclic oligosaccharides, which were

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produced from enzymatic degradation of starch or starch derivates.13 Compared with

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natural α-CD and β-CD, γ-CD has larger hydrophobic cavities, higher water solubility,

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and more favorable bioavailability. Therefore, there is a growing demand for γ-CD in

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the food, cosmetic, and biomedical industries. Recently, environment-friendly

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γ-CD-based MOFs synthesized through the coordination of γ-CD and K or Na ions

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have been reported.14-16 In the originally reported synthesis, CD-MOFs ranging in size

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of 40–500 µm were prepared at room temperature for a week.17 Subsequently, in order

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to

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cetyltrimethylammonium bromide (CTAB) as an emulsifier has been reported.18

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However, addition of CTAB increased risk of sample contamination.8 The size of

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MOF materials is critical for their various properties and applications. Therefore,

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much effort has been made using microwave or ultrasound, mechanical, and

prepare

small

CD-MOFs,

a

modified

method

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the

addition

of

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sonochemical methods to shorten the incubation time and to create smaller MOF

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crystals.19,20 However, these methods are difficult in manufacture for cost-effective

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and scale-up production. In the previous study, we successfully synthesized small

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CD-MOFs with an average size of 1.8-3.9 µm though seed-mediated method.21

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Although smaller CD-MOFs are obtained, the effective control of particle size is still

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a difficult challenge. Based on the classical crystallization mechanism, the preciseness

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of size control could be ensured by the controlled nucleation and growth.22 Therefore,

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in this study, we hypothesis that the size variation from nanometers to millimeters

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could be controlled by crystal-growth time. Furthermore, in order to obtain more

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perfect crystalline CD-MOFs, we optimized the preparation methods of CD-MOFs

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using seed-mediated growth combined with anti-solvent method. The addition of

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anti-solvent induces supersaturation, and the longitudinal variations of interfacial

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tension provide a driving force for the rapid formation of CD-MOF crystals. The

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convenient nucleation control method developed in this study has not been reported.

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Resveratrol (Res) is a natural nonflavonoid polyphenol compound found in plants,

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food, and beverages.23 It has attracted great interest because of its many beneficial

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biological effects, such as lipid metabolism modulation,23 low-density lipoprotein

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protection from oxidative and free radical damage,24 and anticancer and antimicrobial

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activities.25,26 However, this compound suffers from poor stability. Res exists in two

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isomeric forms, namely, cis and trans, and only trans-Res is biologically active.

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Trans-Res has limited stability under the influence of light, temperature and certain

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pH levels, which can cause isomerization or degradation.27 In recent years, Res has

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been encapsulated by employing various matrices, such as liposomes,28 proteins,29 and

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CDs.30 However, there are as yet no reports on the encapsulation of Res in CD-MOFs

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and the stability of Res in such a system. Thus, this study aimed to conduct the rapid

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synthesis of size-controlled CD-MOFs based on SNPs and to demonstrate the

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enhancement of the stability and controlled release of Res encapsulated in the

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CD-MOFs.

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MATERIALS AND METHODS

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Materials. γ-CD and Res were obtained from Sigma Co., Ltd (Shanghai, China).

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Waxy maize starch, absolute ethanol, and methanol were purchased from Sinopharm

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Chemical Reagent Co. Ltd. (Shanghai, China).

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Synthesis of γ-CD-MOFs based on SNP seeds. The SNPs seeds were prepared

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following the method of Sun et al.31 The γ-CD-MOFs were prepared by mixing γ-CD

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(0.25 mmol) with KOH (2 mmol) in 10 mL pure water with the pre-addition of 5 mL

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MeOH. Then 10 mg of SNP seeds were dispersed in above solution. The mixed

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solution was filtered with a organic filter membrane (0.45 µm), followed by vapor

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diffusion at 50 °C for 1–6 h. Afterwards, 15 mL of MeOH was added drop-wise (0.25

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mL/min) into the solution to trigger the precipitation. The treatment conditions were

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selected based on pre-experiment results, different amounts of MeOH (15-60 mL)

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were selected as anti-solvent, so that the small and uniform particles would be

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obtained. Finally, the MOF crystals were collected and washed three times with

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absolute MeOH, and dried at 45 °C overnight.

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Characterization. The atomic force microscopy (AFM) morphology of SNPs

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seeds was observed following the method reported by Wang et al.32 The scanning

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electron microscopy (SEM) morphology of γ-CD-MOFs obtained at different times

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was observed using the method of Qiu et al.21 The particle size of γ-CD-MOF crystals

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were obtained by Image J 1.45 software, accurately by choosing at least 100 MOF

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particles from different SEM micrographs. The X-ray diffraction patterns of

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γ-CD-MOF crystals were analyzed using a Bruker X-ray diffractometer (D2 PHASER,

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Bruker AXS Inc., Germany) following the method reported by Chen, Tian, Sun, Cai,

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Ma & Jin.33 The cytotoxicity of the CD-MOF crystals was determined using

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undifferentiated Caco-2 cells as described previously.34

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Res loading and Stabilization. The inclusion experiments were performed

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according to the method of Moussa et al.,35 with some modifications. Briefly, 20 mg

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γ-CD-MOF crystals obtained after 6 h were ultrasonic dispersed in 5 ml of absolute

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ethanol. Res (4 mg) dissolved in absolute ethanol was added to obtain a final 14 µM

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concentration in dark places. Then, the crystals were centrifuged and washed thrice

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with absolute ethanol, and the same amount of water or absolute ethanol was added.

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The interactions and steady state between the γ-CD-MOFs and Res were determined

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by using an ultraviolet-visible (UV-vis) spectrophotometer (Shimadzu-2600, Kyoto,

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Japan) at different time intervals (0–14 h).

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In vitro release. The in vitro release of Res from Res-loaded γ-CD-MOFs was

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determined by the dialysis method, as described by Qiu et al.36 In brief, 10 mg of

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Res-loaded γ-CD-MOFs were redispersed in 10 mL of release media and were placed

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into the dialysis bag (molecular cut off, 10 kDa), surrounded by 150 mL different

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media (pH 1.2 HCl solution, pH 7.4 and 6.8 phosphate buffer) to simulate the

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different physiological pH conditions at 37 °C with a constant gentle stirring. At

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pre-determined time points (0-24 h), the amount of Res released in the three different

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medium was determined by UV-vis spectroscopy (at 304 nm). The cumulative release

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was quantified as follows: Cumulative release (%) =

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The amount of Res released × 100 Total amount of Res

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Statistical analysis. All the experimental data were presented as mean values ±

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standard deviations in triplicate. Statistical significance analysis was performed by

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Tukey's test using SPSS 17.0 software (SPSS Inc., Chicago, USA). Differences were

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considered at a significance level of 95% (P﹤0.05).

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RESULTS AND DICUSSION

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Morphology and particle size of SNP seeds and γ-CD-MOF. The atomic force

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microscopy (AFM) images and the particle size distributions of SNP seeds are shown

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in Figure 1. The SNP seeds displayed spherical shapes, and the mean diameter was

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approximately 80 nm based on the AFM images (Figure 1). The small SNPs with a

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uniform size could be used as seeds for the synthesis of γ-CD-MOF. The SEM

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morphological images and particle size distributions of the γ-CD-MOFs obtained at

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different times (1–6 h) with and without SNP seeds are presented in Figure 2 and

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Figure 3, respectively. In the absence of SNP seeds, the shapes of the synthesized

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γ-CD-MOF were recorded as a uniform cubic by SEM with an average size of 3–5 µm,

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which was consistent with previous reported with a 3–5 µm particle size

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distribution.10 A slight increase in particle diameter was observed with the increase in

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time, thus indicating that the crystal growth was relatively slow in the absence of SNP

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seeds. However, no significant change in shape was observed in the determination

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time (1–6 h). Interestingly, for the seed-mediated synthesis of γ-CD-MOFs, the size

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variation from nanometer to millimeter could be controlled by crystal growth time.

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Furthermore, the shapes of γ-CD-MOF obtained after 6 h changed from cubic to

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cuboid (Figure 2F). To our knowledge, the morphologies of γ-CD-MOFs are almost

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always cubic in shape, as no similar report has been made up to now. The particle size

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of γ-CD-MOFs based on SNP seeds was in the range of 140–260 nm when the crystal

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growth time was 1 h (Figure 3D). However, the particle size of γ-CD-MOFs obtained

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after 3 and 6 h increased significantly in the range of 400–600 nm (Figure 3E) and

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1–3 µm (Figure 3F), respectively. The formation of small γ-CD-MOFs based on SNP

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seeds should experience following stages: the self-assembly forms nucleus; the crystal

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nucleus growth and coagulation, and the aggregation of γ-CD-MOF crystals.

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Therefore, the size variation from nanometer to millimeter could be controlled by

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crystal growth time.

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X-ray diffraction (XRD) analysis. The XRD patterns of the γ-CD-MOFs

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obtained at different times (1–6 h) with and without SNP seeds are presented in Figure

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4. The characteristic diffraction peaks of γ-CD-MOFs obtained at different times at

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around 4.0, 5.6, 7.0, 13.2, 16.7°, consistent with the literature.8,18 The results showed

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the crystallinity of the γ-CD-MOFs increased with the extension of the synthesis time.

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Similarly, Liu et al.8 reported that the crystallinity of CD-MOFs increased when the

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duration of the preparation was prolonged for 12 h. Interestingly enough, the

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γ-CD-MOFs based on SNPs showed few times higher crystallinity as evidenced by

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the sharp peaks in the XRD patterns. Similarly, Xu et al.,9 reported that the MOFs

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synthesized by a seed-mediated method had high crystallinity. The reason could be

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explained as follows. The γ-CD was easily adsorbed onto the surface of SNP seeds

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due to the interactions of hydrogen bonds between SNPs and CDs. In this way, the

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γ-CDs would be arranged in order more easily, which could accelerate the formation

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of the nucleus. Another possible reason could be because the the addition of seeds

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increased the nucleation number and enabled the crystal growth process to bypass the

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most energy-intensive step.9 Therefore, the CD-MOFs based on SNP seeds showed

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higher crystallinity than the previous method.

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Thermogravimetric analysis. For the γ-CD-MOFs without SNP seeds, the

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thermal degradation temperature increased slightly with the increase in incubation

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time, and the main mass loss step of the γ-CD-MOFs obtained at 1, 3, and 6 h

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occurred in the range of 223.4 °C–332.4 °C, 223.6 °C–333.9 °C, and

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224.9 °C–336.8 °C, respectively. However, compared with that of CD-MOFs, the

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thermal degradation temperature of γ-CD-MOFs with SNP seeds decreased (Figure 5),

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and their main mass loss step occurred in the range of 204.6 °C–325.8 °C,

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217.4 °C–332.2 °C, and 223.8 °C–343.7 °C, respectively. The reduction of molecular

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weight could be the main factor that lowered the thermal stability. Similarly, Sun et

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al.,31 reported that SNPs displayed decreased thermal stability because of the lower

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molecular weight than that of native starch. When the crystallization time was

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increased from 1 to 6 h, the thermal stability of CD-MOFs with SNP seeds increased

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significantly, thus indicating that a perfect crystalline structure was formed, consistent

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with the results on crystallinity.

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Fourier transformation infrared spectroscopy (FTIR) analysis. The FTIR of

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SNP seeds, γ-CD and γ-CD-MOFs are presented in Figure 6. The strong absorption

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peak at 3700–3000 cm−1 was attributed to the O–H stretching vibration of the SNP

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seeds, γ-CD, and γ-CD-MOFs. Compared with native γ-CD, the γ-CD-MOF crystals

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without SNP seeds had a low wavelength. However, the O–H bands of γ-CD-MOFs

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based on SNP seeds shifted to a shorter wavelength, from 3416 cm-1 (γ-CD) to 3380

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cm-1 (1 h), 3368 cm-1 (3 h), and 3355 cm-1 (6 h), indicating that the hydrogen bonds

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between molecular chains were stronger. This result demonstrated SNP seeds had an

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interaction to the γ-CD-MOFs through the hydrogen bonding between molecular

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chains. Similarly, Zhang et al.37 reported that the O–H bands shifted to a shorter

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wavelength, indicating that hydrogen bonds were enhanced.

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Cytotoxicity. The cell viability of CD-MOFs with and without SNP seeds and

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CD-MOFs obtained by adding CTAB is shown in Figure 7. The CD-MOFs

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synthesized exhibited a high viability of cells (> 98%) in a low concentration (< 500

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µg/mL). Even with a high concentration of CD-MOFs reaching 1000 µg/mL, the

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viability of cells was maintained above 95%. This result indicated that the CD-MOFs

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based on SNP seeds were safe and nontoxic. To create small CD-MOF crystals, a

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modified method by the addition of CTAB was reported previously.18 However,

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CD-MOFs synthesized by the addition of CTAB exhibited low toxicity, and the cell

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viability decreased significantly (only about 82%) when the concentrations increased

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from 500 µg/mL to 1000 µg/mL. Therefore, the seed-mediated method provides a

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green and safe way to fabricate CD-MOFs.

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N2 adsorption isotherms analysis. The nitrogen adsorption and desorption

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isotherms were determined by using the Micrometrics ASAP2010 system. Compared

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with the CD-MOFs without seeds obtained at 6 h, the γ-CD-MOFs synthesized based

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on SNP seeds obtained at 3 h and 6 h exhibited a higher N2 uptake (Figure 8).

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However, the γ-CD-MOFs synthesized in a short time had little N2 adsorption (not

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shown) because of imperfect crystallization, consistent with the results on crystallinity.

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The measured pore diameter of γ-CD-MOFs synthesized were in the range of

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2.12-3.24 nm, which shows a characteristic of typical mesoporous materials. The

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γ-CD-MOFs with SNP seeds obtained at 6 h showed maximize BET (Langmuir)

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surface areas of 916.2 (1228.6) m2/g, which could be due to more perfect crystalline

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structure, indicating the porous material could be used as an delivery carriers for food,

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medicine and biomedical industry. Similarly, Liu et al.,8 reported that the theoretical

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BET surface areas of γ-CD-MOFs was 1030 m2/g.

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Stabilization of Res encapsulated in γ-CD-MOF crystals. The stability of Res

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in the CD-MOF crystals based on SNP seeds obtained after 6 h in an aqueous medium

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and ethanol was investigated, and the results are shown in Figure 9. The UV-vis

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spectra of the dissolved Res-loaded CD-MOFs were recorded for 14 h. The MOF

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crystals did not absorb in the range of measures, consistent with previous reports.38

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However, Res had strong absorbance with two peaks at about 305 nm and 320 nm,

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respectively, mainly because of the presence of the trans isomer and biologically

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inactive cis forms of Res. In the ethanol system, the difference between two peaks

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observed was more obvious than in the aqueous solution, indicating that Res was

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more stable in absolute ethanol. In the aqueous medium, the peak at 320 nm

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disappeared after 2 h; this disappearance could be due to the degradation of Res.

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Similarly, the stabilization of Res with CD was reported by Kumar et al.,38 who found

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that Res was relatively stable in organic solvents like ethanol than in aqueous

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solutions. Figure 10 compares the absorbance intensity reduction plots of Res and Res

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encapsulated in γ-CD-MOF crystals in different solvents. A significant reduction was

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observed with the increase in time, indicating that Res was quite unstable. In the Res

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system, almost 60% of the Res degraded rapidly in an aqueous medium after 12 h

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(Figure 10). However, only 32% of the Res was degraded in absolute ethanol. Note

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that the γ-CD-MOF crystals slowed the rate of degradation and that only about 40%

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and 19% of the Res was degraded in aqueous solutions and absolute ethanol,

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respectively, at the determined time; this result could be due to the protection of

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γ-CD-MOFs against degradation. Similarly, Moussa et al.,35 reported that the stability

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of curcumin was enhanced because of the incorporation within the pores of the

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CD-MOF crystals.

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The cumulative release of Res loaded CD-MOFs. The cumulative release

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profile of free Res and Res loaded CD-MOFs are shown in Figure 11. Compared to

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free Res, the Res loaded CD-MOFs showd a remarkable decreased in the percent of

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released Res (Figure 11). In the first 2 hours, the Res loaded CD-MOFs released only

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13% of Res, showing a slow release in acidic pH (1.2). The release amounts of Res

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increased with incubation time, and approximately 25% of the Res was released from

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the CD-MOFs after 6 h. In contrast, the free Res showed a burst release in which

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above 85% of Res was released in the first 6 h. For Res loaded CD-MOFs, the slow

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release was maintained until 24 h. This slow-release behaviour of Res loaded

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CD-MOFs could be attributed to the formation of compact structure, which could

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restrict the Res diffusion capacity for the medium. This result suggested that

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CD-MOFs may serve as effective delivery carriers for controlled Res release systems.

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In summary, we reported the synthesis of size-controlled CD-MOFs based on

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SNP seeds for the first time, which provided simple, green and cost effective strategy

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to fabricate CD-MOFs. The size variation from nanometer (140–260 nm) to

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millimeter (1–3 µm) could be controlled by crystal growth time. Compared with

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CD-MOFs without SNP seeds, the crystallinity of the γ-CD-MOFs based on SNP

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seeds was higher as evidenced by the sharp peaks in the XRD patterns. Therefore, the

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method of seed-mediated is a more facile and efficient alternative to the previous

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method. Moreover, the cell cytotoxicity results indicated that the CD-MOFs based on

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SNP seeds were relatively safe. The stability of Res was substantially enhanced

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because of the incorporation within the pores of the CD-MOF crystals. Furthermore,

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Res loaded CD-MOFs exhibited a consequently sustained release within 24 h. The

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size-controlled CD-MOFs based on SNP seeds could be used as delivery carriers for

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drug or active component controlled-release systems.

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Conflict of interest

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No conflicts of interest are declared for any of the authors.

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Acknowledgements

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This work was supported by Postgraduate Research & Practice Innovation

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Program of Jiangsu Province (KYCX18_1758), national first-class discipline program

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of Food Science and Technology (JUFSTR20180203).

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REFERENCES

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(1) Lu, W., Yuan, D., Makal, T. A., Wei, Z., Li, J. R., & Zhou, H. C. Highly porous

281

metal-organic framework sustained with 12-connected nanoscopic octahedra.

282

Dalton T., 2013, 42, 1708-1714.

283

(2) Martins, R. G., Sales, D. C. S., Filho, N. M. L., & Abreu, C. A. M. Development of

284

a system of natural gas storage governed by simultaneous processes of

285

adsorption–desorption. Adsorption-j Int. Adsorption Soc., 2015, 21, 523-531.

286

(3) Mulfort, K. L., & Hupp, J. T. Chemical reduction of metal-organic framework

287

materials as a method to enhance gas uptake and binding. J. Am. Chem. Soc.,

288

2007, 129, 9604-9605.

289

(4) Gu, Z. Y., & Yan, X. P. Metal-organic framework MIL-101 for high-resolution

290

gas-chromatographic separation of xylene isomers and ethylbenzene. Angew.

291

Chem., 2010, 49, 1477.

292

(5) Cui, J., Gao, N., Wang, C., Zhu, W., Li, J., Wang, H., Seidel, P., Ravoo, B. J., & Li,

293

G. Photonic metal-organic framework composite spheres: a new kind of optical

294

material with self-reporting molecular recognition. Nanoscale, 2014, 6,

295

11995-12001.

296

(6) Kumar, P., Kumar, P., Bharadwaj, L. M., Paul, A. K., & Deep, A. Luminescent

297

nanocrystal metal organic framework based biosensor for molecular recognition.

298

Inorg. Chem. Commun., 2014, 43, 114-117.

299

(7) Li, H., Lv, N., Li, X., Liu, B., Feng, J., Ren, X., Guo, T., Chen, D., Fraser, S. J., &

300

Gref, R. Composite CD-MOF nanocrystals-containing microspheres for

ACS Paragon Plus Environment

Page 16 of 35

Page 17 of 35

Journal of Agricultural and Food Chemistry

301

sustained drug delivery. Nanoscale, 2017, 9, 7454–7463.

302

(8) Liu, B., Li, H., Xu, X., Xue, L., Lv, N., Singh, V., Stoddart, J. F., York, P., Xu, X.,

303

& Gref, R. Optimized synthesis and crystalline stability of γ-cyclodextrin

304

metal-organic frameworks for drug adsorption. Int. J. Pharm., 2016, 514,

305

212-219.

306

(9) Xu, H. Q., Wang, K., Ding, M., Feng, D., Jiang, H. L., & Zhou, H. C.

307

Seed-Mediated Synthesis of Metal-Organic Frameworks. J. Am. Chem. Soc.,

308

2016, 138, 5316-5320.

309

(10) Xu, X., Wang, C., Li, H., Li, X., Liu, B., Singh, V., Wang, S., Sun, L., Gref, R., &

310

Zhang, J. Evaluation of drug loading capabilities of γ-cyclodextrin-metal organic

311

frameworks by high performance liquid chromatography. J Chromatogr. A, 2017,

312

1488, 37-44.

313

(11) Fu, C. P., Lirio, S., Liu, W. L., Lin, C. H., & Huang, H. Y. A novel type of matrix

314

for surface-assisted laser desorption–ionization mass spectrometric detection of

315

biomolecules using metal-organic frameworks. Anal. Chim. Acta, 2015, 888,

316

103-109.

317

(12) Sha, J. Q., Wu, L. H., Li, S. X., Yang, X. N., Zhang, Y., Zhang, Q. N., & Zhu, P. P.

318

Synthesis and structure of new carbohydrate metal–organic frameworks and

319

inclusion complexes. J Mol. Struct., 2015, 1101, 14-20.

320

(13) Kurkov, S. V., & Loftsson, T. Cyclodextrins. Int J Pharm, 2013, 453, 167-180.

321

(14) Smaldone, R. A., Forgan, R. S., Furukawa, H., et al. Metal–Organic Frameworks

322

from Edible Natural Products. Angew Chem Int Ed Engl, 2010, 49, 8535-8535.

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Journal of Agricultural and Food Chemistry

323

(15) Gassensmith, J., Furukawa, H., Smaldone, R. A., et al. Strong and Reversible

324

Binding of Carbon Dioxide in a Green Metal-Organic Framework. J. Am. Chem.

325

Soc. 2011, 133(39):15312-15315.

326 327

(16) Hartlieb, K. J. Holcroft, J. M. , Moghadam, P. Z., et al. CD-MOF: A Versatile Separation Medium. J. Am. Chem. Soc. 2016, 138, 2292-2301.

328

(17) Smaldone, R. A., Forgan, R. S., Furukawa, H., Gassensmith, J. J., Slawin, A. M.,

329

Yaghi, O. M., & Stoddart, J. F. Metal-organic frameworks from edible natural

330

products. Angew. Chem., 2010, 49, 8630-8634.

331

(18) Furukawa, Y., Ishiwata, T., Sugikawa, K., Kokado, K., & Sada, K. Nano- and

332

microsized cubic gel particles from cyclodextrin metal-organic frameworks.

333

Angew. Chem., 2012, 51, 10566-10569.

334

(19) Khan, N. A., & Jhung, S. H. Synthesis of metal-organic frameworks (MOFs)

335

with microwave or ultrasound: Rapid reaction, phase-selectivity, and size

336

reduction. Coordin. Chem. Rev., 2015, 285, 11–23.

337 338

(20) Julien, P., Mottillo, C., & Friščić, T. Metal-organic frameworks meet scalable and sustainable synthesis. Green Chem., 2017, 19, 2729-2747.

339

(21) Qiu, C., Wang, J., Qin, Y., Fan, H., Xu, X., Jin, Z. Green synthesis of

340

cyclodextrin-based metal−organic frameworks through the seed-mediated

341

method for the encapsulation of hydrophobic molecules. J. Agric Food Chem.

342

2018, 16, 4244-4250.

343

(22) Wang, X., Cheng, Q., Yu, Y., & Zhang, X. A general and scalable approach with

344

controlled nucleation and controlled growth for size predicable synthesis of

ACS Paragon Plus Environment

Page 18 of 35

Page 19 of 35

Journal of Agricultural and Food Chemistry

345

nanoscale MOFs. Angew Chem Int Ed Engl. 2018, 10.1002/anie.201803766

346

(23) Lu, Z., Chen, R., Liu, H., Hu, Y., Cheng, B., & Zou, G. Study of the

347

complexation of resveratrol with cyclodextrins by spectroscopy and molecular

348

modeling. J Incl. Phenom. Macro., 2009, 63, 295-300.

349

(24) Brito, P., Almeida, L. M., & Dinis, T. C. The interaction of resveratrol with

350

ferrylmyoglobin and peroxynitrite; protection against LDL oxidation. Free

351

Radical Res., 2002, 36, 621-631.

352 353

(25) Burns, J., Yokota, T., Ashihara, H., Lean, M. E. J., & Crozier, A. Plant foods and herbal sources of resveratrol. J. Agric Food Chem., 2002, 50, 3337-3340.

354

(26) Silva, Â., Duarte, A., Sousa, S., Ramos, A., & Domingues, F. C. Characterization

355

and antimicrobial activity of cellulose derivatives films incorporated with a

356

resveratrol inclusion complex. LWT-Food Sci. Technol., 2016, 73, 481-489.

357

(27) Zupančič, Š., Lavrič, Z., & Kristl, J. Stability and solubility of trans-resveratrol

358

are strongly influenced by pH and temperature. Eur. J. Pharm. & Biopha., 2015,

359

93, 196-204.

360

(28) Coimbra, M., Isacchi, B., Bloois, L. V., Torano, J. S., Ket, A., Wu, X., Broere, F.,

361

Metselaar, J. M., Rijcken, C. J. F., & Storm, G. Improving solubility and

362

chemical stability of natural compounds for medicinal use by incorporation into

363

liposomes. Int. J. Pharm., 2011, 416, 433-442.

364

(29) Joye, I. J., Davidov-Pardo, G., & Mcclements, D. J. Encapsulation of resveratrol

365

in biopolymer particles produced using liquid antisolvent precipitation. Part 2:

366

Stability and functionality. Food Hydrocolloid, 2015, 49, 127-134.

ACS Paragon Plus Environment

Journal of Agricultural and Food Chemistry

367

(30) Kaur, K., Uppal, S., Kaur, R., Agarwal, J., & Mehta, S. K. Energy efficient, facile

368

and cost effective methodology for formation of an inclusion complex of

369

resveratrol with hp-β-CD. New J Chem., 2015, 39, 8855-8865.

370

(31) Sun, Q., Li, G., Dai, L., Ji, N., & Xiong, L. Green preparation and

371

characterisation of waxy maize starch nanoparticles through enzymolysis and

372

recrystallisation. Food Chem., 2014, 162, 223-228.

373

(32) Wang, Q., Crofts, A. R., & Padua, G. W. Protein−lipid interactions in zein films

374

investigated by surface plasmon resonance. J. Agric. Food Chem, 2003, 51,

375

7439-7444.

376

(33) Chen, L., Tian, Y., Sun, B., Cai, C., Ma, R., & Jin, Z. Measurement and

377

characterization of external oil in the fried waxy maize starch granules using

378

ATR-FTIR and XRD. Food Chem. 2018, 242, 131-138.

379

(34) Ji, N., Hong, Y., Gu, Z., Cheng, L., Li, Z., & Li, C. Binary and tertiary complex

380

based on short-chain glucan and proanthocyanidins for oral insulin delivery. J.

381

Agric. Food Chem. 2017, 65, 8866−8874.

382

(35) Moussa, Z., Hmadeh, M., Abiad, M. G., Dib, O. H., & Patra, D. Encapsulation of

383

curcumin in cyclodextrin-metal organic frameworks: Dissociation of loaded

384

CD-MOFs enhances stability of curcumin. Food Chem., 2016, 212, 485−494.

385

(36) Qiu, C., Chang, R., Yang, J., Ge, S., Xiong, L., & Zhao, M., et al. Preparation and

386

characterization of essential oil-loaded starch nanoparticles formed by short

387

glucan chains. Food Chem. 2017, 221, 1426−1433.

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Journal of Agricultural and Food Chemistry

388

(37) Zhang, H. X., Tian, Y. Q., Bai, Y. X., Xu, X. M., & Jin, Z. Y. Structure and

389

properties of maize starch processed with a combination of α–amylase and

390

pullulanase. Int. J. Biol. Macromol., 2013, 52, 38–44.

391

(38) Kumar, R., Kaur, K., Uppal, S., & Mehta, S. K. Ultrasound processed

392

nanoemulsion: A comparative approach between resveratrol and resveratrol

393

cyclodextrin inclusion complex to study its binding interactions, antioxidant

394

activity and UV light stability. Ultrason. Sonochem., 2017, 37, 478-489.

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Figure Captions Figure 1 Atomic force microscopy images of the short linear chain SNPs. Figure 2 SEM morphology images of γ-CD-MOF crystals obtained at different times of 1 h (A), 3 h (B), and 6 h (C), and γ-CD-MOF crystals with added SNP seeds obtained at different times of 1 h (D), 3 h (E), and 6 h (F).

Figure 3 Statistics of the particle size distributions of γ-CD-MOF crystals obtained at different times of 1 h (A), 3 h (B), and 6 h (C), and γ-CD-MOF crystals with added SNP seeds obtained at different times of 1 h (D), 3 h (E), and 6 h (F).

Figure 4 XRD of γ-CD-MOF crystals with and without added SNP seeds obtained at different times (1, 3, and 6 h, respectively).

Figure 5 Thermogravimetric analysis curves of γ-CD-MOF crystals with and without added SNP seeds.

Figure 6 Fourier transformation infrared spectroscopy curves of SNP seeds, γ-CD, and γ-CD-MOF crystals with and without added SNP seeds.

Figure 7 In vitro cell viability of Caco-2 cells against γ-CD-MOF crystals. Figure 8 Nitrogen adsorption–desorption isotherm of γ-CD-MOF crystals with and without added SNP seeds.

Figure 9 UV-visible absorption spectra of Res degradation in an aqueous medium (A: Res; B: Res-loaded γ-CD-MOF) and ethanol (C: Resveratrol; D: Res-loaded γ-CD-MOF) at different determined times (0→5: 0, 2, 4, 6, 9, and 14 h, respectively).

Figure 10 Degradation ratio of Res in an aqueous medium and ethanol at different determined times (0, 2, 4, 6, 9, and 14 h, respectively).

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Figure 11 Release profile of Res and Res loaded CD-MOFs.

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Add seeds

γ-CD

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Resveratrol (Res) Nucleation

Res in water Res in ethanol Res loaded MOFs in water Res loaded MOFs in ethanol

1.0

Controlled growth

0.9

A0/A

0.8

Short amylose seeds

0.7 0.6 0.5 0.4 0.3 0

2

4

6

8

10

12

14

16

Time (h)

Stabilization of Res loaded MOFs

γ-CD-MOFs

Scheme 1. Schematic representation of the size-controlled synthesis of γ-CD-MOFs through facile and green seed-mediated method.

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Figure 1 Atomic force microscopy images of the short linear chain SNPs.

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D

A

5 µm

1 µm

E

B

5 µm

C

1 µm

F

5 µm

3 µm

Figure 2 SEM morphology images of γ-CD-MOF crystals obtained at different times of 1 h (A), 3 h (B), and 6 h (C), and γ-CD-MOF crystals with added SNP seeds obtained at different times of 1 h (D), 3 h (E), and 6 h (F).

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50

A Percentage (%)

Percentage (%)

50 40 30 20 10

D

40 30 20 10

0

0 0

1

2

3

4

5

6

7

8

9

10

0

100 200 300 400 500 600 700 800 900 1000

Size (µm)

Size (nm) 50

B

E Percentage (%)

Percentage (%)

50 40 30 20

30 20 10

10

0

0 0

1

2

3

4

5

6

7

8

9

0

10

100 200 300 400 500 600 700 800 900 1000

Size (nm)

Size (µm)

50

50

C

F Percentage (%)

Percentage (%)

40

40 30 20 10

40 30 20 10

0 0

1

2

3

4

5

6

Size (µm)

7

8

9

10

0 0

1

2

3

4

5

6

7

8

9

10

Size (µm)

Figure 3 Statistics of the particle size distributions of γ-CD-MOF crystals obtained at different times of 1 h (A), 3 h (B), and 6 h (C), and γ-CD-MOF crystals with added SNP seeds obtained at different times of 1 h (D), 3 h (E), and 6 h (F).

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CD-MOFs Seeds 6 h

Intensity

CD-MOFs Seeds 3 h CD-MOFs Seeds 1 h CD-MOFs 6 h CD-MOFs 3 h CD-MOFs 1 h 0

5

10

15

20

25

30

35

40

? (° ) 2θ2 (º)

Figure 4 XRD of γ-CD-MOF crystals with and without added SNP seeds obtained at different times (1, 3, and 6 h, respectively).

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100 CD-MOFs Seeds 1h

80

CD-MOFs Seeds 3h

Weight (%)

CD-MOFs Seeds 6h

60 CD-MOFs 1h CD-MOFs 3h CD-MOFs 6h

40 20 0 0

100

200

300

400

500

600

O

Temperature ( C)

Figure 5 Thermogravimetric analysis curves of γ-CD-MOF crystals with and without added SNP seeds.

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Relative Intensity (%)

3162

3368 3380 3371 3403 3414

4000

SNP Seeds CD

3416 3355

3500

3000

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CD-MOFs Seeds 6h CD-MOFs Seeds 3h CD-MOFs Seeds 1h CD-MOFs 6h CD-MOFs 3h CD-MOFs 1h

2500

2000

cm

1500

1000

500

-1

Figure 6 Fourier transformation infrared spectroscopy curves of SNP seeds, γ-CD, and γ-CD-MOF crystals with and without added SNP seeds.

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CD-MOFs 1h CD-MOFs Seeds 1h CD-MOFs 6h CD-MOFs Seeds 6h CD-MOFs CTAB 6 h

100

Cell viability (%)

80 60 40 20 0 0

250 125 500 Concentration (µg/mL)

1000

Figure 7 In vitro cell viability of Caco-2 cells against γ-CD-MOF crystals.

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Quantity Adsorbed (cm3/g STP)

300

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CD-MOFs-6 h with SNP seeds

250 CD-MOFs-3 h with SNP seeds

200

150 CD-MOFs-3 h without Seeds

100

50 0.0

0.2

0.4

0.6

0.8

1.0

Relative Pressure (P/Po)

Figure 8 Nitrogen adsorption–desorption isotherm of γ-CD-MOF crystals with and without added SNP seeds.

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B

A 1.0

1.0

0 0.8

0.6

Absorbance

Absorbance

0 0.8 5

0.4 0.2

5

0.4 0.2 0.0

0.0 -0.2 300

1.0

0.6

350

400

450

-0.2 500

300

W avelength (nm )

350

C

1.0

D

450

500

0

0.8 0

0.8

Absorbance

Absorbance

400

Wavelength (nm)

0.6 5 0.4 0.2 0.0

5 0.6 0.4 0.2 0.0

300

350

400

W avelength (nm)

450

500

300

350

400

450

500

W avelength (nm)

Figure 9 UV-visible absorption spectra of Res degradation in an aqueous medium (A: Res; B: Res-loaded γ-CD-MOF) and ethanol (C: Resveratrol; D: Res-loaded γ-CD-MOF) at different determined times (0→5: 0, 2, 4, 6, 9, and 14 h, respectively).

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Res in water Res in ethanol Res loaded MOFs in water Res loaded MOFs in ethanol

1.0 0.9

0.8

A0/A

0.7

0.6 0.5

0.4 0.3 0

2

4

6

8

10

12

14

16

Time (h)

Figure 10 Degradation ratio of Res in an aqueous medium and ethanol at different determined times (0, 2, 4, 6, 9, and 14 h, respectively).

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Res loaded CD-MOFs Res

Cumulative release (%)

100

80

60

pH 6.8 pH 1.2

40 pH 7.4 20

0 0

4

8

12

16

20

24

28

Time (h)

Figure 11 Release profile of Res and Res loaded CD-MOFs.

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