Site-directed decapsulation of bolaamphiphilic vesicles with enzymatic cleavable surface groups

Popov, Mary; Grinberg, Sarina; Linder, Charles; Waner, Tal; Levi-Hevroni, Bosmat; Deckelbaum, Richard J.; Heldman, Eliahu

doi:10.1016/j.jconrel.2011.12.022

Cited by 20 publications

(27 citation statements)

References 41 publications

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“…Also, the presence of the double bonds in the alkyl chain of the bolaamphiphilic skeleton of GLH-20 does not seem to significantly affect the hydrolysis rate, as bolaamphiphiles with different moieties within the alkyl chain of their skeleton are well hydrolyzed by AChE. 25,39 Moreover, the surface head group of GLH-20 is also hydrolyzed by AChE when the bolaamphiphile is aggregated into vesicles, 25 and the alkyl chain of the bolaamphiphilic skeleton has no access to the enzyme as it is buried deep in the monolayer membrane (see below results obtained with intact vesicles described in Figure 9). These results exclude a significant contribution of the alkyl chain of the bolaamphiphilic skeleton to the difference in the hydrolysis rate of the ACh head group of GLH-20 and GLH-32 and leave the alkyl chain pendant, which is adjacent to the head group, as the most likely candidate that affects the hydrolysis rate.…”

Section: ∆ [H+]mentioning

confidence: 98%

“…25 Briefly, the pH of the bolaamphiphile, suspended in water, was measured for several minutes until a stable reading was achieved. Then 0.1 unit of AChE was added with a continuous pH measurement for 11 minutes.…”

Section: Measurements Of Ach Head Group Hydrolysismentioning

confidence: 99%

“…23 Recently, we have described novel nanovesicles made of synthetic bolaamphiphiles with acetylcholine (ACh) head groups 16,24 that are capable of releasing their encapsulated content upon exposure to acetylcholinesterases (AChEs). [25][26][27] When AChE hydrolyzes the ACh surface groups of such vesicles, the vesicular structure is disrupted, resulting in a release of the encapsulated material. Since the hydrolysis of the head groups causes the disruption of the vesicular structure, 25 we postulated that the rate of the head group hydrolysis would determine the release rate of the encapsulated drug.…”

Section: Introductionmentioning

confidence: 99%

“…[25][26][27] When AChE hydrolyzes the ACh surface groups of such vesicles, the vesicular structure is disrupted, resulting in a release of the encapsulated material. Since the hydrolysis of the head groups causes the disruption of the vesicular structure, 25 we postulated that the rate of the head group hydrolysis would determine the release rate of the encapsulated drug. We further hypothesized that the rate of the head group hydrolysis may be varied by changing the molecular environment around the ACh head group, and thus affecting the interaction between the ACh head group and the hydrolyzing enzyme, AChE.…”

Section: Introductionmentioning

confidence: 99%

“…controlled release from bolaamphiphilic vesicles groups attached to bolaamphiphiles via the nitrogen atom of the choline moiety were hydrolyzed regardless if the alkyl chain of the skeleton contained 30 atoms, 39 or 38 atoms, 25 suggesting that long alkyl chains that contain 30 atoms or more enable the ACh head group (which is covalently attached to them), to reach the bottom of the catalytic gorge of AChE so that they can be hydrolyzed. Due to steric considerations, it is expected that the interaction between the ACh head group and the active site of AChE would be influenced by chemical moieties, which are situated near the head group.…”

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confidence: 99%

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Steric environment around acetylcholine head groups of bolaamphiphilic nanovesicles influences the release rate of encapsulated compounds

Stern¹,

Shaubi²,

Popov³

et al. 2014

IJN

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Two bolaamphiphilic compounds with identical acetylcholine (ACh) head groups, but with different lengths of an alkyl chain pendant adjacent to the head group, as well as differences between their hydrophobic skeleton, were investigated for their ability to self-assemble into vesicles that release their encapsulated content upon hydrolysis of their head groups by acetylcholinesterase (AChE). One of these bolaamphiphiles, synthesized from vernolic acid, has an alkyl chain pendant of five methylene groups, while the other, synthesized from oleic acid, has an alkyl chain pendant of eight methylene groups. Both bolaamphiphiles formed stable spherical vesicles with a diameter of about 130 nm. The ACh head groups of both bolaamphiphiles were hydrolyzed by AChE, but the hydrolysis rate was significantly faster for the bolaamphiphile with the shorter aliphatic chain pendant. Likewise, upon exposure to AChE, vesicles made from the bolaamphiphile with the shorter alkyl chain pendant released their encapsulated content faster than vesicles made from the bolaamphiphile with the longer alkyl chain pendant. Our results suggest that the steric environment around the ACh head group of bolaamphiphiles is a major factor affecting the hydrolysis rate of the head groups by AChE. Attaching an alkyl chain to the bolaamphiphile near the ACh head group allows self-assembled vesicles to form with a controlled release rate of the encapsulated materials, whereas shorter alkyl chains enable a faster head group hydrolysis, and consequently faster release, than longer alkyl chains. This principle may be implemented in the design of bolaamphiphiles for the formation of vesicles for drug delivery with desired controlled release rates.

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Section: ∆ [H+]mentioning

confidence: 98%

Section: Measurements Of Ach Head Group Hydrolysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Steric environment around acetylcholine head groups of bolaamphiphilic nanovesicles influences the release rate of encapsulated compounds

Stern¹,

Shaubi²,

Popov³

et al. 2014

IJN

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Multifunctional Nanoparticles Self‐Assembled from Small Organic Building Blocks for Biomedicine

2016

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Supramolecular self-assembly shows significant potential to construct responsive materials. By tailoring the structural parameters of organic building blocks, nanosystems can be fabricated, whose performance in catalysis, energy storage and conversion, and biomedicine has been explored. Since small organic building blocks are structurally simple, easily modified, and reproducible, they are frequently employed in supramolecular self-assembly and materials science. The dynamic and adaptive nature of self-assembled nanoarchitectures affords an enhanced sensitivity to the changes in environmental conditions, favoring their applications in controllable drug release and bioimaging. Here, recent significant research advancements of small-organic-molecule self-assembled nanoarchitectures toward biomedical applications are highlighted. Functionalized assemblies, mainly including vesicles, nanoparticles, and micelles are categorized according to their topological morphologies and functions. These nanoarchitectures with different topologies possess distinguishing advantages in biological applications, well incarnating the structure-property relationship. By presenting some important discoveries, three domains of these nanoarchitectures in biomedical research are covered, including biosensors, bioimaging, and controlled release/therapy. The strategies regarding how to design and characterize organic assemblies to exhibit biomedical applications are also discussed. Up-to-date research developments in the field are provided and research challenges to be overcome in future studies are revealed.

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Supramolecular Nanoassemblies of an Amphiphilic Porphyrin–Cyclodextrin Conjugate and Their Morphological Transition from Vesicle to Network

Zhao

Zhang

Sun

et al. 2015

Chemistry A European J

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An amphiphilic compound, 5-(4'-dodecyloxyphenyl)-10,15,20-tri(permethyl-β-CD)-modified Zn(II)-porphyrin (1; β-CD = β-cyclodextrin), was synthesized by means of the click reaction of an alkylated Zn-porphyrin derivative with 6-deoxy-6-azidopermethyl-β-CD. The complexation between 1 and tetrasodium tetraphenylporphyrintetrasulfonate (5) with different molar ratios led to the formation of two distinctly different nanoarchitectures, which were proven to be vesicle and network aggregates, respectively, by using dynamic light scattering, scanning electron microscopy, transmission electron microscopy, and atomic force microscopy. On the basis of the results of the time-dependent TEM studies, fluorescence, and NMR spectroscopic measurements, we have determined that the mechanism of the morphology transition from vesicles to networks is controlled by the stepwise complexation of 1 with 5. Furthermore, these supramolecular nanoarchitectures show the controlled- release property of doxorubicin as potential candidates for drug delivery.

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Site-directed decapsulation of bolaamphiphilic vesicles with enzymatic cleavable surface groups

Cited by 20 publications

References 41 publications

Steric environment around acetylcholine head groups of bolaamphiphilic nanovesicles influences the release rate of encapsulated compounds

Steric environment around acetylcholine head groups of bolaamphiphilic nanovesicles influences the release rate of encapsulated compounds

Multifunctional Nanoparticles Self‐Assembled from Small Organic Building Blocks for Biomedicine

Supramolecular Nanoassemblies of an Amphiphilic Porphyrin–Cyclodextrin Conjugate and Their Morphological Transition from Vesicle to Network

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