Research Article www.acsami.org
Voltage-Responsive Controlled Release Film with Cargo Release SelfMonitoring Property Based on Hydrophobicity Switching Xiangyu Jiao,† Yanan Li,‡ Fengyu Li,‡ Ruijuan Sun,† Wenqian Wang,† Yongqiang Wen,*,† Yanlin Song,‡ and Xueji Zhang*,† †
Research Center for Bioengineering & Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China ‡ Key Laboratory of Green Printing, Institute of Chemistry Chinese Academy of Sciences (ICCAS), Beijing Engineering Research Center of Nanomaterials for Green Printing Technology, Beijing National Laboratory for Molecular Sciences (BNLMS), Beijing 100190, P. R. China S Supporting Information *
ABSTRACT: Herein, voltage-responsive controlled release film was constructed by grafting ferrocene on the mesoporous inverse opal photonic crystal (mIOPC). The film achieved free-blockage controlled release and realized the monitoring of cargo release without external indicator. Free-blockage was attributed to the voltage switchable nanovalves which undergo hydrophobic-to-hydrophilic transition when applying voltage. Monitoring of cargo release was attributed to the optical property of mIOPC, the bandgap of mIOPC had a red shift when the solution invaded in. The film was hydrophobic enough to stop solution intrusion. Once the voltage was applied, the film became hydrophilic, leading to invasion of the solution. As a result, the cargos were released and the bandgap of mIOPC was red-shifted. Therefore, in this paper both a free-blockage controlled release film and a release sensing system was prepared. The study provides new insights into highly effective controlled release and release sensing without indicator. KEYWORDS: nano valve, hydrophobicity switching, free-blockage, controlled release, release sensing
1. INTRODUCTION Recently, the research of controlled release of drugs and other bioactive agents from film has received considerable attention. This is in part due to their ability to achieve stimulusdependent and time-controlled release, thus alleviating undesired side effects and enhancing efficacy.1−3 Many of the mechanisms of release have been previously discussed. One of the most obvious one is the degrading or disassembling of the structures.4−9 By controlling the level of degradation or disassembly, tunable controlled release is realized.10,11 But the degrading or degradation of films will contaminate solution. Another way to control the release is modulated the size of nanopores formed by the structure.12,13 However, most of the materials with swell-shrink properties to modulate the nanopores are polymer, which often lack heat and chemical resistance. The most common way to realize controlled release is controlling the physical blockages to leave the nanopores.14−17 However, the blockages which separate from the nanopores are limited by the plugging efficiency and size. The physical blockage is difficult to realize seamless blockage for every nanopore, which results in the unexpected leak of cargos. Moreover, such a physical blockage is difficult to achieve loading of biomacromolecules, because the larger pore diameter © XXXX American Chemical Society
demands larger blocking units, which would raise higher demand on materials and gating ability. Besides, the nanopores will remain open after the blocking units depart from the nanopores in some physical blockage system, which causes unexpected persistently release of cargos. Sergei N. Smirnov and his co-workers have developed a new free-blockage nanovalve based on hydrophobic nanopores.18,19 The hydrophobic nanopores could create an effective natural air plug against water invasion, and the nanovalves were off. When the nanopores changed from hydrophobicity to hydrophilicity under stimulation, the nanovalves turned on. Recently, we constructed a free-blockage release system based hydrophilic/hydrophobic switching of the nanovalves of mesoporous silica nanoparticles.20,21 These release system not only improved the transfer efficiency of drug between tumor cells but also greatly reduced the side effects of the carriers. Furthermore, the release system could repeatedly infect neighboring cells owing to the property of pulsatile release with the change of stimulus. Received: December 20, 2016 Accepted: March 7, 2017 Published: March 7, 2017 A
DOI: 10.1021/acsami.6b16325 ACS Appl. Mater. Interfaces XXXX, XXX, XXX−XXX
Research Article
ACS Applied Materials & Interfaces
Scheme 1. Illustration of the the Process for the Preparation of Voltage-Responsive Controlled Release mIOPC Film and Its Controlled Release Characteristic
(APS), sodium dihydrogen phosphate, acrylic acid, methylbenzene, ethyl acetate, petroleum ether, and dichloromethane were purchased from Sinopharm Chemical Reagent Co., Ltd. Indium tin oxides glass (ITO) ( 4|Δγ | /Dpore = 4|γ cos θ| /Dpore E
(2)
DOI: 10.1021/acsami.6b16325 ACS Appl. Mater. Interfaces XXXX, XXX, XXX−XXX
Research Article
ACS Applied Materials & Interfaces
Figure 6. (a) Voltage controlled release profiles of R6G from mIOPC-0.01 and Fe-mIOPC-0.1. “solution” and “applied voltage” represent the films were in the solutions (without voltage) and applied voltage in the solutions, respectively. (b) The pulsatile release profiles of R6G from mIOPC-0.01. (The arrows pointe represent the ± voltage were applied).
where Pext is the pressure outside of the film, and Pin is the pressure inside, Dpore is the diameter of the pore, Δγ is the surface energy difference between the surface tension of solid/ vapor, γsv, and the surface tension of solid/liquid, γsl. Δγ is related to the surface tension of liquid/vapor interface, γ, and contact angle (CA) on the pore solid, θ, via the Young equation: Δγ = γsv − γs1 = γ cos θ
steeper than that of Fe-mIOPC-0.1, which indicated the hydrophobic-to-hydrophilic switch of Fe-mIOPC-0.01 was faster than that of Fe-mIOPC-0.1. This was because that there were more ferrocene groups on the Fe-mIOPC-0.1, the hydrophobic-to-hydrophilic switch was slow under the same condition when compared with the Fe-mIOPC-0.01 with less ferrocene groups. The result was consistent with the bandgap shift data above. The time difference between the spectrum experiment and the CA experiment was the result of the difference in electrode spacing and membrane-solution contact area. It was the close electrode spacing and small membranesolution contact area that was attributed to the much higher surface current density, which made the conversion from Fe(II) to Fe(III) more easily. 3.3. Voltage Controlled Release Properties. Rhodamine 6G (R6G), a model cargo, which was loaded in the Fe-mIOPC by immersing the Fe-mIOPC in a mixture solution of ethanol/ toluene (1:4) containing R6G. The R6G was loaded on the FemIOPC via weak intermolecular force (Figure S7). Then the Fe-mIOPC-0.01 and Fe-mIOPC-0.1 were immersed into PBS solution with pH 7.0. Fluorescence spectroscopy was used to analyze the release process at 548 nm. As shown in Figure 6a, both R6G from Fe-mIOPC-0.01 and Fe-mIOPC-0.1 did not release until the voltage was applied. This indicated that the nanovalves kept close in the solution without voltage. When the voltage was applied, R6G released step by step. The R6G released from Fe-mIOPC-0.01 was faster than that from FemIOPC-0.1. The release curves were consistent with the bandgap shift data above. It was noteworthy that the fluorescence intensity of Fe-mIOPC-0.01 was higher than that of Fe-mIOPC-0.1. This was caused by the electrooxidation of R6G (Figure S4).36 Briefly, the R6G released from Fe-mIOPC0.1 suffered oxidation for a long time. And the decay of fluorescence intensity of Fe-mIOPC-0.01 and Fe-mIOPC-0.1 was also the result of electrooxidation. The slow invasion of solution was a critical feature for the pulsatile release of R6G. Figure 6b shows the increase of fluorescence of R6G during the pulsatile voltage treatment. In this system, solution could not invade the entire nanopore within a few hours. After the positive voltage was applied, the valve opened and the solution invaded in. Then the negative voltage was applied, the valve became off and the solution stopped invading in. However, the nanopores where the
(3)
where γ is the liquid/vapor surface tension. Upon reaching the critical pressure for invasion, ΔP0, the CA exceeds the critical one, θ0. The value of ΔP0 is quite large even for Dpore = 271 nm with a modest advancing CA of θ0 ≈ 92°, its value is ΔP0 = 0.37 bar (γ ≈ 73 mN/m). It means that only the external pressure is 0.36 bar higher than the pressure inside the pores, and the solutions can invade the pores.35 Until the CA becomes smaller than 90°, this air plugs block the nanopores all the time. A pore with variable size (just like IOPC structure), may end up at a pressure which exceeds the critical ΔP0 for Dmax but too low for invading into the narrowing of Dmin.35 The macropores inside the inverse opal structure (75 nm) could bear a pressure of more than 1.39 bar even to a very modest contact angles (θ0 ≈ 92°). The apparent CAs for Fe-mIOPC-0.01 and Fe-mIOPC-0.1 were measured as shown in Figure 5a, where 3.0 μL solution were deposited. Since there were less ferrocene groups on the Fe-mIOPC-0.01, the apparent CA of it was 96°, smaller than that of Fe-mIOPC-0.1, 108°. It can be observed that the droplets were more stable without voltage, while the CAs decreased quickly for both Fe-mIOPC-0.01 and Fe-mIOPC-0.1, and the CAs of Fe-mIOPC-0.01 decreased faster. To further analyze the change of CAs under voltage, the change of CAs (kept platinum electrode inserted no matter whether voltage was applied or not) were recorded (Figure 5b). Both the CAs of Fe-mIOPC-0.01 and Fe-mIOPC-0.1 were decreased slowly when the voltage was not applied. The slopes of CA changing curves were nearly equal, which meant the speed of decrease of CAs were almost the same. It was because the decrease of CAs was caused by the water evaporation. To demonstrate the change of CAs with time directly and exclude the influence of tiny differences between different films, voltage was applied on the same film. Once the voltage was applied, the CAs decreased quickly, and the slope of CA curves of Fe-mIOPC-0.01 was F
DOI: 10.1021/acsami.6b16325 ACS Appl. Mater. Interfaces XXXX, XXX, XXX−XXX
Research Article
ACS Applied Materials & Interfaces
Figure 7. (a) Results of antibacterial test by CB solutions released from mIOPC-0.01 under different conditions (indicated on the top) at different times (indicated at the left). (b) Reflectance spectra of mIOPC-0.01 loaded with CB vary with time when the voltage applied.
were modified with ferrocene to prepare convertible hydrophobic nanovalves. Cargoes were trapped in the nanopores of the film in solutions because of the hydrophobic effect. Once the voltage was applied, the Fe(II) groups were oxidized, which triggered the cargos releasing resulted from nanovalves were changed to hydrophilic. Moreover, the reflected light of the film had a red shift with the cargoes being released, which realized the monitor of release level without external indicator. These advantages makes it a promising candidate for applications requiring controllable gating, efficient sensing, and steady structure. Furthermore, the multifunctional film is expected to find many applications, such as sensing release of biomacromolecules and sequential release, owing to the unique hierarchically structure of mIOPC and the efficient freeblockage nanovalve. Therefore, our approach to creating a controlled release mIOPC film based on hydrophobicity switching provides new perspectives in the application of controlled release and photonic crystal.
solutions had invaded could not become dry again, thus the R6G in the infiltrative part still released a period of time via diffusion. The inner part of the nanopores would be hydrophobic to prevent the solution invading deeper in the nanopores, until the positive voltage was applied again. Thus, the pulsatile release was achieved with the sequential change of voltage over a long period of time. It indicated that the film had tunable controlled release feature, which means the releasing procedure could be paused when the stimulus disappeared. To confirm full functionality of the film, we investigated the release of Carbenicillin (CB) in an antibacterial test. E. coli, which is associated with many infections of humans and other living creatures, was chosen as a model target for antibacterial tests. In Figure 7a, with the E. coli serving as control, antibacterial activity from Fe-mIOPC-0.01, Fe-mIOPC-0.01 loaded CB (no voltage applied), Fe-mIOPC-0.01 applied voltage (without CB loading) ,and CB (100 μg/mL) were compared with the Fe-mIOPC-0.01 loaded with CB and applied voltage. The Fe-mIOPC-0.01 loaded CB (no voltage applied) exhibit no bactericidal activity, which proved that the nanovalve had an excellent plugging capacity. The mIOPC-0.01 applied voltage (without CB loading) also exhibited no bactericidal activity, and this demonstrated voltage had no obvious impacts on bactericidal activity. The Fe-mIOPC-0.01 applied voltage loaded with CB showed an effective bactericidal activity when applied voltage. We also test the influence of voltage on the antibacterial activity of CB (Figure S5). The results proved that the 0.8 V voltage has little influence on the antibacterial activity of CB compared with CB in normal pressure and temperature, but the higher voltage, 1.5 V, had an obvious influence on the antibacterial activity of CB. Meanwhile, the reflection spectra of the film was measured during release of CB (Figure 7b). The bandgap of Fe-mIOPC-0.01 with CB loading was 500 nm, which had a red shift compared with Fe-mIOPC-0.01 without cargoes. This was result from the increase of the effective refractive index nm (eq 1). It was obvious that the bandgap had a red shift about 17 nm during the releasing process of CB. This proved that the film could monitor the cargo release level efficiently.
■
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsami.6b16325. NMR and IR of ferrocene silane (PDF)
■
AUTHOR INFORMATION
Corresponding Authors
*Fax: +86-10-82375840. E-mail:
[email protected] (Y.W.). *E-mail:
[email protected] (X.Z.). ORCID
Yongqiang Wen: 0000-0002-1924-4166 Yanlin Song: 0000-0002-0267-3917 Notes
The authors declare no competing financial interest.
■
4. CONCLUSIONS In summary, a voltage controlled free-blockage release mIOPC film with ability to self-monitor the release of cargoes was achieved through hydrophobic to hydrophilic conversion of nanopores. The mIOPCs with hierarchically porous structure
ACKNOWLEDGMENTS
The authors would like to thank the NSFC (51373023, 21171019), Beijing Natural Science Foundation (2172039, 2122038), and the Fundamental Research Funds for the Central Universities and NCET-11-0584. G
DOI: 10.1021/acsami.6b16325 ACS Appl. Mater. Interfaces XXXX, XXX, XXX−XXX
Research Article
ACS Applied Materials & Interfaces
■
by controlling the wetting behavior of hydrophobic surface. ACS Nano 2014, 8 (1), 744−751. (22) Xu, M.; Feng, D.; Dai, R.; Wu, H.; Zhao, D.; Zheng, G. Synthesis of hierarchically nanoporous silica films for controlled drug loading and release. Nanoscale 2011, 3 (8), 3329−33. (23) Zhao, Y.; Xie, Z.; Gu, H.; Zhu, C.; Gu, Z. Bio-inspired variable structural color materials. Chem. Soc. Rev. 2012, 41 (8), 3297−3317. (24) Pal, S.; Yadav, A. R.; Lifson, M. A.; Baker, J. E.; Fauchet, P. M.; Miller, B. L. Selective virus detection in complex sample matrices with photonic crystal optical cavities. Biosens. Bioelectron. 2013, 44, 229− 234. (25) Kuang, M.; Wang, J.; Jiang, L. Bio-inspired photonic crystals with superwettability. Chem. Soc. Rev. 2016, 45 (24), 6833−6854. (26) Dong, X.; Wei, C.; Liu, T.; Lv, F.; Qian, Z. Real-Time Fluorescence Tracking of Protoporphyrin Incorporated Thermosensitive Hydrogel and Its Drug Release in Vivo. ACS Appl. Mater. Interfaces 2016, 8 (8), 5104−5113. (27) Shao, D.; Zhang, X.; Liu, W.; Zhang, F.; Zheng, X.; Qiao, P.; Li, J.; Dong, W.-f.; Chen, L. Janus Silver-Mesoporous Silica Nanocarriers for SERS Traceable and pH-Sensitive Drug Delivery in Cancer Therapy. ACS Appl. Mater. Interfaces 2016, 8 (7), 4303−4308. (28) Liu, L.; Tang, Y. H.; Dai, S.; Kleitz, F.; Qiao, S. Z. Smart surfaceenhanced Raman scattering traceable drug delivery systems. Nanoscale 2016, 8 (25), 12803−12811. (29) Mora, L.; Chumbimuni-Torres, K. Y.; Clawson, C.; Hernandez, L.; Zhang, L.; Wang, J. Real-time electrochemical monitoring of drug release from therapeutic nanoparticles. J. Controlled Release 2009, 140 (1), 69−73. (30) Wang, J. X.; Wen, Y. Q.; Ge, H. L.; Sun, Z. W.; Zheng, Y. M.; Song, Y. L.; Jiang, L. Simple fabrication of full color colloidal crystal films with tough mechanical strength. Macromol. Chem. Phys. 2006, 207 (6), 596−604. (31) Schetter, B.; Speiser, B. Reaction of ferrocenecarboxylic acid with N,N′-disubstituted carbodiimides: synthesis, spectroscopic and Xray crystallographic analysis of N,N′-disubstituted N-ferrocenoylureas and identification of a one-pot coupling reagent for the formation of ferrocenecarboxamides in a non-aqueous solvent. J. Organomet. Chem. 2004, 689 (9), 1472−1480. (32) Ge, J.; Yin, Y. Responsive photonic crystals. Angew. Chem., Int. Ed. 2011, 50 (7), 1492−522. (33) Jiao, X.; Li, Y.; Li, F.; Wang, W.; Wen, Y.; Song, Y.; Zhang, X. pH-Responsive nano sensing valve with self-monitoring state property based on hydrophobicity switching. RSC Adv. 2016, 6 (57), 52292− 52299. (34) Shang, K.; Wang, X.; Sun, B.; Cheng, Z.; Ai, S. β-cyclodextrinferrocene host−guest complex multifunctional labeling triple amplification strategy for electrochemical immunoassay of subgroup J of avian leukosis viruses. Biosens. Bioelectron. 2013, 45, 40−45. (35) Smirnov, S.; Vlassiouk, I.; Takmakov, P.; Rios, F. Water Confinement in Hydrophobic Nanopores. Pressure-Induced Wetting and Drying. ACS Nano 2010, 4 (9), 5069−5075. (36) Khalfaoui, N.; Boutoumi, H.; Khalaf, H.; Oturan, N.; Oturan, M. A. Electrochemical Oxidation of the Xanthene Dye Rhodamine 6G by Electrochemical Advanced Oxidation Using Pt and BDD Anodes. Curr. Org. Chem. 2012, 16 (18), 2083−2090.
REFERENCES
(1) Langer, R. New methods of drug delivery. Science 1990, 249 (4976), 1527−1533. (2) Siepmann, J.; Siepmann, F. Stability of aqueous polymeric controlled release film coatings. Int. J. Pharm. 2013, 457 (2), 437−445. (3) Hartono, S. B.; Phuoc, N. T.; Yu, M.; Jia, Z.; Monteiro, M. J.; Qiao, S.; Yu, C. Functionalized large pore mesoporous silica nanoparticles for gene delivery featuring controlled release and codelivery. J. Mater. Chem. B 2014, 2 (6), 718−726. (4) Song, J.; Jańczewski, D.; Ma, Y.; van Ingen, L.; Sim, C. E.; Goh, Q.; Xu, J.; Vancso, G. J. Electrochemically controlled release of molecular guests from redox responsive polymeric multilayers and devices. Eur. Polym. J. 2013, 49 (9), 2477−2484. (5) Smith, R. C.; Riollano, M.; Leung, A.; Hammond, P. T. Layer-bylayer platform technology for small-molecule delivery. Angew. Chem., Int. Ed. 2009, 48 (47), 8974−8977. (6) Prasannan, A.; Tsai, H.-C.; Chen, Y.-S.; Hsiue, G.-H. A thermally triggered in situ hydrogel from poly(acrylic acid-co-N-isopropylacrylamide) for controlled release of anti-glaucoma drugs. J. Mater. Chem. B 2014, 2 (14), 1988−1997. (7) Min, J.; Braatz, R. D.; Hammond, P. T. Tunable staged release of therapeutics from layer-by-layer coatings with clay interlayer barrier. Biomaterials 2014, 35 (8), 2507−2517. (8) Hsu, B. B.; Jamieson, K. S.; Hagerman, S. R.; Holler, E.; Ljubimova, J. Y.; Hammond, P. T. Ordered and kinetically discrete sequential protein release from biodegradable thin films. Angew. Chem., Int. Ed. 2014, 53 (31), 8093−8098. (9) Hu, X.; Liu, S.; Zhou, G.; Huang, Y.; Xie, Z.; Jing, X. Electrospinning of polymeric nanofibers for drug delivery applications. J. Controlled Release 2014, 185, 12−21. (10) Wood, K. C.; Boedicker, J. Q.; Lynn, D. M.; Hammond, P. T. Tunable drug release from hydrolytically degradable layer-by-layer thin films. Langmuir 2005, 21 (4), 1603−1609. (11) Cui, W.; Li, X.; Zhu, X.; Yu, G.; Zhou, S.; Weng, J. Investigation of drug release and matrix degradation of electrospun poly (DLlactide) fibers with paracetanol inoculation. Biomacromolecules 2006, 7 (5), 1623−1629. (12) Kharlampieva, E.; Kozlovskaya, V.; Sukhishvili, S. A. Layer-byLayer Hydrogen-Bonded Polymer Films: From Fundamentals to Applications. Adv. Mater. 2009, 21 (30), 3053−3065. (13) De Geest, B. G.; Sanders, N. N.; Sukhorukov, G. B.; Demeester, J.; De Smedt, S. C. Release mechanisms for polyelectrolyte capsules. Chem. Soc. Rev. 2007, 36 (4), 636−649. (14) Tokarev, I.; Minko, S. Stimuli-Responsive Porous Hydrogels at Interfaces for Molecular Filtration, Separation, Controlled Release, and Gating in Capsules and Membranes. Adv. Mater. 2010, 22 (31), 3446− 3462. (15) Kazemzadeh-Narbat, M.; Lai, B. F.; Ding, C.; Kizhakkedathu, J. N.; Hancock, R. E.; Wang, R. Multilayered coating on titanium for controlled release of antimicrobial peptides for the prevention of implant-associated infections. Biomaterials 2013, 34 (24), 5969−5977. (16) Ehlert, N.; Badar, M.; Christel, A.; Lohmeier, S. J.; Luessenhop, T.; Stieve, M.; Lenarz, T.; Mueller, P. P.; Behrens, P. Mesoporous silica coatings for controlled release of the antibiotic ciprofloxacin from implants. J. Mater. Chem. 2011, 21 (3), 752−760. (17) Xu, J.; Zhou, X.; Gao, Z.; Song, Y. Y.; Schmuki, P. Visible-LightTriggered Drug Release from TiO2 Nanotube Arrays: A Controllable Antibacterial Platform. Angew. Chem., Int. Ed. 2016, 55 (2), 593−597. (18) Smirnov, S. N.; Vlassiouk, I. V.; Lavrik, N. V. Voltage-gated hydrophobic nanopores. ACS Nano 2011, 5 (9), 7453−7461. (19) Rios, F.; Smirnov, S. N. pH Valve Based on Hydrophobicity Switching. Chem. Mater. 2011, 23 (16), 3601−3605. (20) Wang, W.; Chen, L.; Xu, L. P.; Du, H.; Wen, Y.; Song, Y.; Zhang, X. A free-blockage controlled release system based on the hydrophobic/hydrophilic conversion of mesoporous silica nanopores. Chem. - Eur. J. 2015, 21 (6), 2680−2685. (21) Chen, L.; Wang, W.; Su, B.; Wen, Y.; Li, C.; Zhou, Y.; Li, M.; Shi, X.; Du, H.; Song, Y.; Jiang, L. A light-responsive release platform H
DOI: 10.1021/acsami.6b16325 ACS Appl. Mater. Interfaces XXXX, XXX, XXX−XXX
