Supramolecular Amphiphilic Assembly Formed by the Complexation

Jun 16, 2019 - Control experiments showed that free calixpyridinium and Alimta solutions .... of Alimta in the presence of different concentrations of...
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Article Cite This: Langmuir 2019, 35, 9020−9028

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Supramolecular Amphiphilic Assembly Formed by the Complexation of Calixpyridinium with Alimta Kui Wang,* Qi-Qi Wang, Mi-Ni Wang, Siyang Xing,* Bolin Zhu,* and Ze-Hao Zhang Tianjin Key Laboratory of Structure and Performance for Functional Molecules, MOE Key Laboratory of Inorganic-Organic Hybrid Functional Material Chemistry, College of Chemistry, Tianjin Normal University, Binshuixi Road 393, Xiqing District, Tianjin 300387, China

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S Supporting Information *

ABSTRACT: In this work, the host−guest interaction between calixpyridinium and anionic anticancer drug Alimta was studied in aqueous media. Spherical supramolecular amphiphilic assembly rather than simple complex was accidentally fabricated by the complexation of calixpyridinium with Alimta. It is the third kind of anionic guest to be discovered to form the higher-order assembly by the complexation of calixpyridinium besides polyanionic guest and anionic gemini surfactant guest. The finding of this assembly approach supplies a new idea to construct various self-assembly architectures in water via the complexation of calixpyridinium with anionic drugs. The resulting calixpyridinium−drug assemblies may also have the potential to adjust the effects of drugs.

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polyanions32−34 or anionic gemini surfactants.35 Although calixpyridinium has been known as a good host for anionic guest in water, the study on the host−guest interaction between calixpyridinium and anionic drug has not been reported up to now. Pemetrexed (brand name Alimta36) is the first approved drug to treat malignant pleural mesothelioma.37 It is also a second-line drug for the treatment of nonsmall cell lung cancer.38 Herein, we report a study on the host−guest interaction between calixpyridinium and anionic anticancer drug Alimta in aqueous media. Spherical supramolecular amphiphilic assembly rather than simple complex was accidentally fabricated by the complexation of calixpyridinium with Alimta (Scheme 1). It is the third kind of anionic guest to be discovered to form higher-order assembly by the complexation of calixpyridinium besides polyanionic guest and anionic gemini surfactant guest. Macrocyclic host-based supramolecular amphiphilic assembly can be tailored to fabricate new topological structures and fulfill multiple applications.39,40 Therefore, the discovery of this assembly approach supplies a new idea to construct various self-assembly architectures in water via the complexation of calixpyridinium with anionic drugs. The resulting calixpyridinium−drug assemblies may also have the potential to adjust the effects of drugs.

INTRODUCTION At present, as the second leading cause of death following cardiovascular and cerebrovascular diseases, cancer is one of the most serious diseases threatening human life. According to a previous estimated report, 18.1 million people would be diagnosed with cancer and 9.6 million cancer deaths would occur in 2018 on a global scale.1 Therefore, finding effective ways to reduce the death rate of cancer has been a hot topic. The most common and effective way for the treatment of cancer is chemotherapy.2 It uses anticancer drugs to kill cancer cells. However, most anticancer drugs also have strong toxicity to normal cells. To reduce the side effects of anticancer drugs, drug delivery systems attracted a lot of attention.3−8 These drug carriers loaded anticancer drugs inside, protected the active ingredient from premature degradation, and released them at the targeted sites. However, the construction of drug delivery systems needs ingenious design and complicated synthesis of building blocks. The method of supramolecular inclusion by macrocyclic hosts paves a smart way to adjust the effects of drugs. Cucurbituril,9−18 cyclodextrin,19,20 pillararene,21−23 and psulfonatocalixarene24−26 are the frequently used macrocycles in this field. However, it is noted that most of these macrocycles are perfect receptors for cationic and neutral substrates. The supramolecular inclusion of anionic drugs by macrocyclic host to adjust the effects of anionic drugs has been explored much less frequently. In fact, anionic drugs are also quite important, such as anionic anticancer drug Alimta. In recent years, cationic macrocyclic calixpyridinium has attracted more and more attention because it has shown good binding abilities for anionic guests in water.27−31 Furthermore, higher-order assemblies rather than simple complexes were constructed by the complexation of calixpyridinium with © 2019 American Chemical Society

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EXPERIMENTAL SECTION

Materials Preparation. Alimta was purchased from Aladdin. 1Methylpyridinium chloride and β-cyclodextrin were purchased from TCI. Glyphosate and 1,3,6,8-pyrenetetrasulfonic acid tetrasodium salt (PyTS) were purchased from Sigma-Aldrich. All of these compounds were used without further purification. Calixpyridinium was Received: May 6, 2019 Revised: June 7, 2019 Published: June 16, 2019 9020

DOI: 10.1021/acs.langmuir.9b01336 Langmuir 2019, 35, 9020−9028

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Langmuir Scheme 1. Schematic Illustration of the Supramolecular Amphiphilic Assembly Formed by the Complexation of Calixpyridinium with Alimta

Figure 1. Dependence of the optical transmittance at 350 nm on the calixpyridinium concentration in the presence of 0.10 mM (a), 0.15 mM (b), and 0.20 mM (c) Alimta. respectively. The formation of the calixpyridinium−Alimta supramolecular amphiphilic assemblies would achieve a balance over 2 h. The aqueous solution was adjusted to different pH values by HCl or NaOH. The pH values were verified on a Sartorius pp-20 pH meter calibrated with two standard buffer solutions. NMR Spectroscopy. 1H NMR spectra were recorded with a Bruker AV400 spectrometer at 298.15 K. UV/Vis Spectra. UV/vis spectra and the optical transmittance of the aqueous solution were measured in a quartz cell (light path 10 mm) on a Persee TU-1810 spectrophotometer. High-Resolution Transmission Electron Microscopy (TEM) Experiments. High-resolution transmission electron microscopy

synthesized and purified according to a previously reported procedure.27 It was identified by 1H and 13C NMR spectroscopy in D2O, performed on a Bruker AV400 spectrometer, and by X-ray crystallographic analysis, performed on a Bruker APEX-II CCD diffractometer. Preparation of the calixpyridinium−Alimta supramolecular amphiphilic assemblies: Alimta was first dissolved in double-distilled water, and then calixpyridinium solution was mixed dropwise in the Alimta solution to get the dynamic calixpyridinium− Alimta supramolecular amphiphilic assembly. The resulting concentrations of calixpyridinium and Alimta in the calixpyridinium−Alimta supramolecular amphiphilic assembly are 0.15 and 0.30 mM, 9021

DOI: 10.1021/acs.langmuir.9b01336 Langmuir 2019, 35, 9020−9028

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Figure 2. Dependence of the electrical conductivity on the calixpyridinium concentration in the presence of 0.10 mM (a), 0.15 mM (b), and 0.20 mM (c) Alimta in water. (TEM) images were acquired using a Talos F200X high-resolution transmission electron microscope operating at an accelerating voltage of 200 kV. Dynamic Light Scattering (DLS) Measurements. Dynamic light scattering (DLS) experiments were measured by NanoBrook 173 Plus at a scattering angle of 90°. Electrical Conductivity Measurements. Electrical conductivity was measured by a DDJ-A automatic electrical conductivity instrument. Centrifuge Tests. Centrifuge tests were performed on a TG16MW centrifugal machine.

values of calixpyridinium obtained by electrical conductivity were in the same order of magnitude as those obtained by UV/ vis spectroscopy. It is noted that free calixpyridinium and Alimta could not self-aggregate in aqueous solution under the above experimental conditions (Figure S2). Although different concentrations of Alimta can all induce aggregation of calixpyridinium, it is necessary to determine the stoichiometry between calixpyridinium and Alimta for fabricating calixpyridinium−Alimta binary supramolecular amphiphilic aggregates. The continuous variation method was used to measure the stoichiometry by monitoring the dependence of the optical transmittance at 350 nm on the molar ratio of calixpyridinium (Figure S3). The total concentration of calixpyridinium and Alimta was kept constant at 0.20 mM, and the molar ratio was varied between 0 and 1. As shown in Figure 3, a minimum was identified in the Job’s plot for a 0.3 molar ratio of calixpyridinium, indicating that the stoichiometry of calixpyridinium and Alimta for fabricating the

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RESULTS AND DISCUSSION The optical transmittance of the Alimta solution in the presence of different concentrations of calixpyridinium was first measured (Figure S1). As shown in Figure 1, the addition of a small amount of calixpyridinium could not lead to an obvious change in the optical transmittance of the Alimta solution over 350 nm. With the addition of more calixpyridinium, the optical transmittance of the Alimta solution over 350 nm began to decrease dramatically because of the turbidity generated by the supramolecular amphiphilic assembly between calixpyridinium and Alimta. The Alimta-complexation-induced critical aggregation concentration (CAC) of calixpyridinium could therefore be obtained by observing the inflection point on the plot of the optical transmittance at 350 nm versus the concentrations of calixpyridinium (Figure 1): 47.5 μM at 0.10 mM Alimta, 12.0 μM at 0.15 mM Alimta, and 11.9 μM at 0.20 mM Alimta. Electrical conductivity was used to confirm the Alimtacomplexation-induced CAC of calixpyridinium. As shown in Figure 2, in the presence of Alimta, the concentrationdependent titrations of calixpyridinium showed sharper inflection points, which were identified as the Alimtacomplexation-induced CAC of calixpyridinium: 27.7 μM at 0.10 mM Alimta, 11.5 μM at 0.15 mM Alimta, and 31.2 μM at 0.20 mM Alimta. The Alimta-complexation-induced CAC

Figure 3. Job’s plot for calixpyridinium and Alimta in water. [Calixpyridinium] + [Alimta] = 0.20 mM. 9022

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inflection point on the plot of the optical transmittance at 350 nm versus the concentrations of calixpyridinium (Figure 4): 33.4 μM calixpyridinium−66.8 μM Alimta. To ensure complete aggregation between calixpyridinium and Alimta, further studies on the calixpyridinium−Alimta assembly were focused on a concentration that is far higher than the CAC of the 1:2 calixpyridinium−Alimta complex: 0.15 mM calixpyridinium−0.30 mM Alimta. As shown in Figure 5a, the solution of the calixpyridinium− Alimta complex showed the obvious Tyndall effect, revealing that the self-assembly of calixpyridinium with Alimta could form abundant nanoparticles. Control experiments showed that free calixpyridinium and Alimta solutions could not show the Tyndall effect, indicating that free calixpyridinium and Alimta could not self-aggregate under the same conditions. Furthermore, the replacement of calixpyridinium by its building subunit 1-methylpyridinium could also not selfassemble with Alimta, which was confirmed by the Tyndall effect (Figure 5a) and the optical transmittance (Figure 5b). This suggests that the cyclic structure of calixpyridinium was also a key factor for the amphiphilic aggregation between calixpyridinium and Alimta. High-resolution transmission electron microscopy (TEM) and dynamic light scattering (DLS) were then used to determine the structure and size of the calixpyridinium−Alimta supramolecular amphiphilic aggregates. The TEM image showed that the morphology of the aggregates was regular spherical structure (Figures 5c and S5) and the average diameter of the spheres measured by DLS is 224.6 nm (Figure 5d). 1 H NMR spectroscopy has been frequently used to deduce the host−guest binding mode by analyzing complexationinduced chemical shift changes (Δδ).41 Herein, to obtain the

binary supramolecular amphiphilic aggregates is 1:2, which is charge matching for calixpyridinium and Alimta. Next, the optical transmittance of different concentrations of the calixpyridinium−Alimta solution with a fixed 1:2 stoichiometry was measured to determine the CAC of the 1:2 calixpyridinium−Alimta complex for fabricating the binary supramolecular amphiphilic aggregates (Figure S4). As shown in Figure 4, the addition of a small amount of calixpyridinium−

Figure 4. Dependence of the optical transmittance at 350 nm on the calixpyridinium concentration in the calixpyridinium−Alimta solution with a fixed 1:2 stoichiometry.

Alimta complex could not lead to an obvious change in the optical transmittance over 350 nm. With the addition of more calixpyridinium−Alimta complex, the optical transmittance over 350 nm began to decrease dramatically because of the turbidity generated by the self-assembly between calixpyridinium and Alimta. The CAC of the 1:2 calixpyridinium− Alimta complex could therefore be obtained by observing the

Figure 5. (a) Photograph showing the Tyndall effect of free calixpyridinium (I), free Alimta (II), calixpyridinium + Alimta (III), and 1methylpyridinium chloride + Alimta (IV). (b) Optical transmittance of calixpyridinium, Alimta, calixpyridinium + Alimta, and 1-methylpyridinium chloride + Alimta in water. (c) High-resolution TEM image of the calixpyridinium−Alimta assemblies. (d) DLS data of the calixpyridinium−Alimta assemblies. [Calixpyridinium] = 0.15 mM, [Alimta] = 0.30 mM, and [1-methylpyridinium chloride] = 0.60 mM. 9023

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electrostatic interactions, such as succinate,28 fumarate,28 αketoglutaric acid,30 and acidic amino acid,30 the additional charge-transfer interactions besides the electrostatic interactions between calixpyridinium and Alimta may be a key factor for the construction of the higher-order spherical calixpyridinium−Alimta supramolecular amphiphilic assembly. The binding ability of calixpyridinium with Alimta was further estimated by the competitive binding of Alimta with calixpyridinium in calixpyridinium−glyphosate and calixpyridinium−1,3,6,8-pyrenetetrasulfonic acid tetrasodium salt (PyTS) solution, respectively, because the binding ability of calixpyridinium with glyphosate and PyTS is weak31 and strong,29 respectively. The binding constant of calixpyridinium with glyphosate is in the order of magnitude of 102 M−1,31 and that with PyTS is high up to 106 M−1.29 As shown in Figure S6a, the addition of 2 equiv of Alimta in the calixpyridinium− PyTS solution could not disturb its optical transmittance, implying that Alimta could not competitively bind with calixpyridinium in calixpyridinium−PyTS solution. However, as shown in Figure S6b, the addition of 2 equiv of Alimta in the calixpyridinium−glyphosate solution leaded to a decrease in its optical transmittance, implying that Alimta could competitively bind with calixpyridinium in the calixpyridinium−glyphosate solution to form calixpyridinium−Alimta supramolecular amphiphilic aggregates. The two competitive binding experimental results implied that the binding ability of calixpyridinium with Alimta was moderate. The stability of the calixpyridinium−Alimta supramolecular amphiphilic aggregates at room temperature was further studied. As shown in Figures S7 and 7a, there was no appreciable change in the transmittance spectra of the calixpyridinium−Alimta solution over at least 1 day at room temperature. Centrifuging the calixpyridinium−Alimta solution for 1 min at 1000 rpm could also not disturb its optical transmittance and the Tyndall effect as well (Figure 7b). Both experimental results implied that the calixpyridinium−Alimta supramolecular amphiphilic aggregates were quite stable at room temperature. It is well-known that the stability of the aggregates formed by electrostatic interactions would be seriously affected by salt. Therefore, the stability of the calixpyridinium−Alimta supramolecular amphiphilic aggregates was also studied in the NaCl solution. As shown in Figures S8 and 8a, there was no appreciable change in the transmittance spectra of the calixpyridinium−Alimta solution with the addition of NaCl from 0 to 1 mM. The addition of

binding structure of calixpyridinium with Alimta, the 1H NMR spectra of calixpyridinium, Alimta, and calixpyridinium−Alimta complex were recorded in D2O solutions. As can be seen from Figure 6, a large upfield shift was observed for the Hb, Hc, Hd,

Figure 6. 1H NMR spectra of Alimta (bottom), calixpyridinium (top), and calixpyridinium−Alimta complex (middle) in D2O solutions. Inset: the color of the D2O solution of Alimta (bottom), calixpyridinium (top), and calixpyridinium−Alimta complex (middle). [Calixpyridinium] = 5 mM and [Alimta] = 10 mM.

and He proton signal of calixpyridinium upon complexation with Alimta, while the Ha proton signal of calixpyridinium almost did not shift, which indicated that Alimta was bound outside the cavity of calixpyridinium. On the other hand, as can be seen from Figure 6, the shift values for the H1−H8 proton signals of Alimta upon complexation with calixpyridinium were large, whereas those for the H9 and H10 proton signals of Alimta were even negligible, which indicated that the nitrogen heterocyclic ring, benzene ring, and negatively charged carboxylate connected to H8 are the three possible main binding sites of Alimta with calixpyridinium accompanied by charge-transfer and electrostatic interactions. It is noted that the Alimta solution changed from colorless to yellow upon the addition of calixpyridinium (Figure 6), which further indicated the definite existence of a charge-transfer interaction between calixpyridinium and Alimta. Compared with other reported dicarboxylate guests that could only form simple complexes upon complexation with calixpyridinium driven only by

Figure 7. (a) Dependence of the optical transmittance at 350 nm of the calixpyridinium−Alimta assembly on time within 24 h at room temperature in water. (b) Optical transmittance of the calixpyridinium−Alimta assembly before and after centrifugation for 1 min at 1000 rpm in aqueous solution. Inset: the Tyndall effect of the calixpyridinium−Alimta solution before (I) and after centrifugation for 1 min (II). [Calixpyridinium] = 0.15 mM and [Alimta] = 0.30 mM. 9024

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Figure 8. (a) Dependence of the optical transmittance at 350 nm of the calixpyridinium−Alimta assembly on the concentration of NaCl. Inset: the Tyndall effect of the calixpyridinium−Alimta solution in the absence (I) and presence (II) of 0.30 mM NaCl. (b) Dependence of the optical transmittance at 350 nm of the calixpyridinium−Alimta assembly on time within 6 h in the presence of 0.30 mM NaCl. Inset: the Tyndall effect of the calixpyridinium−Alimta assembly immediately after the preparation (I) and 6 h after the preparation in the presence of 0.30 mM NaCl. [Calixpyridinium] = 0.15 mM and [Alimta] = 0.30 mM.

Figure 9. Dependence of the optical transmittance at 350 nm on the calixpyridinium concentration in the presence of 0.10 mM (a), 0.15 mM (b), and 0.20 mM (c) Alimta in the 142 mM NaCl solution.

mM Alimta, 82.7 μM at 0.15 mM Alimta, and 47.8 μM at 0.20 mM Alimta. The obtained Alimta-complexation-induced CAC of calixpyridinium in the 142 mM NaCl solution was of the same order of magnitude as that of pure water, implying that the Alimta-complexation-induced CAC value may be enough for the retentivity in blood. All of these experimental results in NaCl solutions are quite important for biomedical application by using the calixpyridinium−Alimta supramolecular amphiphilic aggregates in a complex biological environment. To determine the driving force behind the supramolecular amphiphilic aggregation between calixpyridinium and Alimta, the temperature responsiveness of the calixpyridinium−Alimta supramolecular amphiphilic aggregates was further studied. As shown in Figure 10, the optical transmittance of the calixpyridinium−Alimta solution obviously increased with an increase in temperature accompanied by the disappearance of the Tyndall effect. It indicated that the supramolecular amphiphilic aggregation between calixpyridinium and Alimta

NaCl could also not disturb the Tyndall effect (Figure 8a). Moreover, there was even no appreciable change in either the transmittance spectra (Figures S9 and 8b) or the Tyndall effect (Figure 8b) for the calixpyridinium−Alimta supramolecular amphiphilic aggregates in the NaCl solution over 6 h. All these experimental results in the NaCl solutions implied that the calixpyridinium−Alimta supramolecular amphiphilic aggregates even have sufficient stability in salt solution. NaCl is the main component in plasma. The average concentration of NaCl in plasma is about 142 mM.42 To study if the Alimtacomplexation-induced CAC of calixpyridinium is suitable for medicinal use, the Alimta-complexation-induced CAC of calixpyridinium in the 142 mM NaCl solution was further measured by observing the optical transmittance of Alimta in the 142 mM NaCl solution in the presence of different concentrations of calixpyridinium (Figure S10). As shown in Figure 9, the Alimta-complexation-induced CAC of calixpyridinium in the 142 mM NaCl solution was 75.0 μM at 0.10 9025

DOI: 10.1021/acs.langmuir.9b01336 Langmuir 2019, 35, 9020−9028

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environment of cancer cell is weak acidic,43 and therefore the aggregation between calixpyridinium and Alimta could also occur in this environment, which is quite important for the adjustment of the effect of anionic anticancer drug Alimta by the aggregation with calixpyridinium. Although macrocyclic cyclodextrin also has the tendency to bind with anionic organic molecules,20 cyclodextrin could not bind with Alimta (Figure S13). This clearly implied that the electrostatic and chargetransfer interactions between the cationic macrocyclic calixpyridinium and the anionic Alimta played a key role in the calixpyridinium−Alimta aggregation. Figure 10. Optical transmittance of the calixpyridinium−Alimta assembly at 22 and 60 °C in water. Inset: the Tyndall effect of the calixpyridinium−Alimta solution at 22 °C (I) and 60 °C (II). [Calixpyridinium] = 0.15 mM and [Alimta] = 0.30 mM.

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CONCLUSIONS

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ASSOCIATED CONTENT

The host−guest interaction between calixpyridinium and the anionic anticancer drug Alimta was studied in aqueous media. Incidentally, the complexation of calixpyridinium with Alimta led to the formation of a higher-order spherical supramolecular amphiphilic assembly rather than a simple complex. It is the third kind of anionic guest to be discovered to form the higherorder assembly by the complexation of calixpyridinium besides polyanionic and anionic gemini surfactant guests. This finding supplies a new idea to construct various supramolecular assemblies in water by the complexation of calixpyridinium with anionic drugs. Furthermore, the resulting calixpyridinium−drug assemblies may also have the potential to adjust the effects of drugs.

was driven by enthalpy. In the light of the van’t Hoff equation, increasing temperature is unfavorable for the aggregation with a negative enthalpy change and, therefore, leads to the disassembly of the aggregates. Because calixpyridinium and Alimta are both pH-sensitive molecules, the suitable pH value range for the construction of the calixpyridinium−Alimta supramolecular amphiphilic aggregates was also studied. The optical transmittance spectra of the calixpyridinium−Alimta solution were recorded at various pH values (Figure S11). As shown in Figure 11, the transmittance at 700 nm first

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.langmuir.9b01336. Optical transmittance of aqueous solutions of calixpyridinium at different concentrations in the presence of Alimta; optical transmittance of aqueous solutions of calixpyridinium and Alimta at different concentrations; optical transmittance of aqueous solutions of calixpyridinium and Alimta with different mixing molar ratios; optical transmittance of aqueous solutions of calixpyridinium−Alimta at different concentrations with a fixed 1:2 stoichiometry; high-resolution TEM image of the calixpyridinium−Alimta assemblies; optical transmittance of calixpyridinium−PyTS and calixpyridinium− glyphosate solution in the absence and presence of Alimta; optical transmittance of the calixpyridinium− Alimta assembly at different time within 24 h; optical transmittance of the calixpyridinium−Alimta assembly at different concentrations of NaCl solution; optical transmittance of the calixpyridinium−Alimta assembly at different times within 6 h in 0.30 mM NaCl solution; optical transmittance of different concentrations of calixpyridinium in 142 mM NaCl solution in the presence of Alimta; optical transmittance of the aqueous solutions of the calixpyridinium−Alimta assembly at different pH values; UV-vis absorption spectra of aqueous solutions of calixpyridinium and Alimta at different pH values; UV−vis absorption spectra of aqueous solution of Alimta in the presence of different concentrations of β-cyclodextrin (PDF)

Figure 11. Dependence of the optical transmittance at 700 nm on the pH value of the calixpyridinium−Alimta aqueous solution. [Calixpyridinium] = 0.15 mM and [Alimta] = 0.30 mM.

decreased with increasing pH until the minimum was reached and then increased with further increasing pH. The suitable pH value range for the construction of the calixpyridinium−Alimta supramolecular amphiphilic aggregates was determined to be 4−6. The possible reason for the disassembly of the calixpyridinium−Alimta supramolecular amphiphilic aggregates under alkaline condition is the partial deprotonation of the methylene bridges in calixpyridinium (Figure S12a), which would lead to a weaker host−guest interaction between calixpyridinium and Alimta because of the reduced positive charge of calixpyridinium from protonated to deprotonated state.33 The possible reason for the disassembly of the calixpyridinium−Alimta supramolecular amphiphilic aggregates under acidic condition is the partial protonation of the anions in Alimta (Figure S12b), which would lead to a weaker host−guest interaction between calixpyridinium and Alimta because of the reduced negative charge of Alimta from the deprotonated to protonated state. It is noted that the living 9026

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (K.W.). *E-mail: [email protected] (S.X.). *E-mail: [email protected] (B.Z.). ORCID

Kui Wang: 0000-0002-0379-3865 Siyang Xing: 0000-0002-6240-0363 Bolin Zhu: 0000-0002-6846-566X Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the National Natural Science Foundation of China (21402141, 21302140, and 21572160), the Natural Science Foundation of Tianjin City (18JCQNJC06700), and the Program for Innovative Research Team in University of Tianjin (TD13-5074) for financial support.

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