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Method Article
The present work describes a method to fabricate micellar nanocrystals, an emerging major class of nanobiomaterials. This method combines top-down electrospray, bottom-up self-assembly, and solvent-based structure control. The fabrication method is largely continuous, can produce high quality products, and possesses an inexpensive means of structure control.
Micellar nanocrystals (micelles with encapsulated nanocrystals) have become an emerging major class of nanobiomaterials. We describe a method of fabricating micellar nanocrystals based on combining top-down electrospray, bottom-up self-assembly, and solvent-based structure control. This method involves first using electrospray to generate uniform ultrafine liquid droplets, each of which functions as a micro-reactor in which self-assembly reaction occurs forming micellar nanocrystals, with the structures (micelle shape and nanocrystal encapsulation) controlled by the organic solvent used. This method is largely continuous and produces high quality micellar nanocrystal products with an inexpensive structure control approach. By using a water-miscible organic solvent tetrahydrofuran (THF), worm-shaped micellar nanocrystals can be produced due to solvent-induced/facilitated micelle fusion. Compared with the common spherical micellar nanocrystals, worm-shaped micellar nanocrystals can offer minimized non-specific cellular uptake, thus enhancing biological targeting. By co-encapsulating multiple nanocrystals into each micelle, multifunctional or synergistic effects can be achieved. Current limitations of this fabrication method, which will be part of the future work, primarily include imperfect encapsulation in the micellar nanocrystal product and the incompletely continuous nature of the process.
Nanocrystals such as semiconductor quantum dots (QDs) and superparamagnetic iron oxide nanoparticles (SPIONs) have demonstrated great potential for biological detection, imaging, manipulation, and therapy1,2,3,4,5,6. Encapsulating one or more nanocrystals into a micelle has been a widely used method to interface nanocrystals with biological environments3,6. The thus-formed micellar nanocrystals (micelles with nanoc....
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Caution: Due to the use of organic solvents, all operations should be done in a chemical fume hood. Due to the use of high electric voltage, avoid body contact with the apparatus when the power supply is on. Use all appropriate safety practices such as using personal protective equipment (safety glasses, gloves, lab coat, full-length pants, and closed-toe shoes). Consult all relevant material safety data sheets (MSDS).
1. Setup of Materials
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Figure 1 shows a schematic summarizing the control of structures (shape and encapsulation) of micellar nanocrystals by the organic solvent used in the production process. Briefly, dichloromethane leads to spherical micelles with no encapsulation of nanocrystals; chloroform leads to spherical micelles with a low encapsulation number of nanocrystals; THF leads to spherical micelles with a high encapsulation number of nanocrystals at a short reaction time and wo.......
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The fabrication method of micellar nanocrystals described in the present work combines top-down electrospray, bottom-up self-assembly, and solvent-based structure control. An effective and convenient quality control method is to use the Taylor cone formed at the coaxial nozzle tip. This is because a properly formed Taylor cone indicates balance (or near balance) between electric force and surface tension, which in turn indicates successful formation of micro-reactors (uniform ultrafine droplets) for the self-assembly rea.......
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The authors have nothing to disclose.
The authors gratefully acknowledge the financial support of a "Thousand Young Global Talents" award from the Chinese Central Government, a "Shuang Chuang" award from the Jiangsu Provincial Government, start-up fund from College of Engineering and Applied Sciences, Nanjing University, China, award from the "Tian-Di" Foundation, grant from the Priority Academic Program Development Fund of Jiangsu Higher Education Institutions (PAPD), grant from the Jiangsu Province Natural Science Fund.
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Name | Company | Catalog Number | Comments |
Hydrophobic quantum dots | Ocean Nanotech | QSP | Solid hydrophobic CdSe/ZnS quantum dots. Peak fluorescence emission wavelength is 605 nm. |
Poly(styrene)-b-poly(ethylene glycol) (PS-PEG) | Sigma-Aldrich | 666476-500MG | Molecular weight of PS segment is 9.5 kDa and that of PEG segment is 18.0 kDa. |
Poly(vinyl alcohol) (PVA) | Sigma-Aldrich | 363170-500G | Molecular weight 13–23 kDa, 87–89% hydrolyzed. |
Tetrahydrofuran (THF) | Sinopharma Chemical Reagent | 80124418 | |
Chloroform | Sinopharma Chemical Reagent | 40007960 | |
Syringe pumps | Bao Ding Shen Chen | SPLab01 | |
Tubing | Shanghei Lai Xing | 2 mm outer diameter and 1.8 mm inner diameter PTFE tubing. | |
Syringes | Yi Ming | 5.CC | 5 mL disposable syringe made of PTFE. |
High voltage power supply | Dong Wen | DW Series | Direct current power supply (0–50 kV range). |
Electrospray coaxial nozzle | Hunan Chang Sha Na Yi | Stainless steel assembly. Inner capillary needle was a 27 gauge (outer diameter 500 μm; inner diameter 300 μm). Outer capillary was a 20 gauge (outer diameter 1,000 μm; inner diameter 500 μm). | |
Vortexer | Xi'an HEB Biotechnology Co., Ltd. China | MX-S | MX-S with wide speed range of 0–2,500 rpm, stepless speed regulation, touch and continuous operations. |
Steel ring | Yiwu Wan Tu | Rings with a range of diameters (0.8–1.8 cm) can be constructued. For example, a 1.3 cm diameter ring was constructed by curling an approximately 25 cm (length) of 0.5-mm diamter (24 gauge, AWG) steel wire. | |
Glass collecting dish | Grainger | 1u5084 | 25-mm height and 120-mm diameter glass dish. |
15 mL centrifuge tube | Jiangsu Xinkang Medical Instrument Co., Ltd. | X-407 | Centrifuge tube is made of transparent polypropylene (PP). |
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