Facile Transfer of Reverse Micelles from the Organic to the Aqueous Phase for Mimicking Enzyme Catalysis and Imaging-Guided Cancer Therapy

Abstract

Reverse micelles (RMs) with confined water pools have been applied in many fields. However, the water insolubility of RMs seriously limits the scope of their application, especially those needed to operate in aqueous environments. Here, we report the first successful transfer of RMs from the organic phase to water phase without disturbing their confined water pools and hydrophobic alkyl region. This transfer was achieved by virtue of a mild host–guest interaction between the hydrophobic tails of interfacial cross-linked reverse micelles (ICRMs) and the hydrophobic cavity of (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD). Benefitting from the maintained confined water pools and the hydrophobic scaffold, the obtained water-soluble ICRMs served as multifunctional nanoplatforms for enzyme-mimicking catalysis and image-guided cancer therapy, which were impossible for normal RMs lacking water solubility or confined pool-buried water-soluble nanoparticles without a hydrophobic alkyl chain. This mild transfer approach thus surmounts the application obstacle of RMs and opens up new avenues for their application in aqueous environments.

Deep Drug Penetration of Nanodrug Aggregates at Tumor Tissues by Fast Extracellular Drug Release

“…The dynamic light scattering (DLS) measurement showed that, after transfer, the AICRM retains a particle size of ≈18 nm, comparable to that before transfer (≈15 nm, Figure 1b). [ 15a ] Representative transmission electron microscopy (TEM) showed that the nanoparticles were evenly dispersed, and diameters of 15–20 nm were consistent with DLS results (Figure 1c). The cross‐linked reverse micelles have good stability in blood environment and resist extreme dilution.…”

“…Amphiphilic molecule 1 was dissolved in a 2:1 v/v trichloromethane/ N , N ‐dimethylacetamide (DMAc) mixture with a W 0 (water‐to‐surfactant molar ratio) of 5 to form the optically clear reverse micelle solution. [ 15 ] The AICRM was obtained by covalently capturing the reverse micelles in the presence of cross‐linker 2 (see the “Experimental Section” for details). Successful capture was verified by 1 H NMR spectroscopy, which showed that the double bond peaks disappeared from 5.5 to 6.0, and all other peaks broadened (Figure S1, Supporting Information).…”

“…AICRM was prepared according to the previously reported procedures with slight modifications. [ 15,16 ] Water (1.8 µL, W 0 = 5) was added to a solution of surfactant 1 (13.7 mg, 0.02 mmol) in chloroform (1.0 mL) and DMAc (0.5 mL). The mixture was slowly stirred at room temperature for 1 min to give an optically clear solution.…”

“…The synthetic procedure of RhB@AICRM was similar to that of AICRM, except that pure water was replaced by an RhB aqueous solution (1.8 µL, 0.05 m ) during the preparation of reverse micelles ( W 0 = 5). [ 15a ] To an organic phase solution of RhB@AICRM, 0.25 mL of DMAc solution of 5‐FU (2.0 mg mL −1 ) was added dropwise with ultrasonication. After UV irradiation, 2 mL of deionized water was added to the solution, and the resulting mixture was extracted into the aqueous phase.…”

Nonpolar Interface Composition in Cetyltrimethylammonium Bromide Reverse Micellar Environments to Control Size and Induce Anisotropy on Gold Nanoparticles

“…RMs with confined water pools have been applied in many fields. Recently it was achieved transfer of RMs from the organic phase to water phase without disturbing their confined water pools and hydrophobic alkyl region providing a suitable environment for newfangled applications such as enzyme‐mimicking catalysis and image‐guided cancer therapy . Regarding the use of RMs as nanoreactors, reactants are solubilized in the water pools in separate micellar solutions to react after mixing, reactions take place as the micelles exchange process inside the droplets (nucleation and growth).…”