trans-2-Aminocyclohexanol-based amphiphiles as highly efficient helper lipids for gene delivery by lipoplexes

Zheng, Yin; Liu, Xin; Samoshina, Nataliya M.; Samoshin, Vyacheslav V.; Franz, Andreas H.; Guo, Xin Dong

doi:10.1016/j.bbamem.2015.08.021

Cited by 16 publications

(25 citation statements)

References 60 publications

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“…Entrapped fluorescent dye (ANTS) and quencher (DPX) were stable at pH 7.4, but were released at pH <5.6 for liposomes containing 25–50 mol% morpholine lipid. Recently, trans ‐2‐aminocyclodecanol (TACH) was introduced into a lipoplex formulation for gene delivery, yielding significantly enhanced pH‐dependent transfection . The cationic lipid 1,2‐dioleoyl‐3‐trimethylammonium‐propane (DOTAP) and TACH‐lipids were formulated with plasmid DNA to form with a pH‐sensitive conformational switch.…”

Section: Ph‐responsive Liposomesmentioning

confidence: 99%

Stimuli‐responsive liposomes for drug delivery

Lee

Thompson

2017

WIREs Nanomed Nanobiotechnol

347

190

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The ultimate goal of drug delivery is to increase the bioavailability and reduce the toxic side effects of the active pharmaceutical ingredient (API) by releasing at a specific site of action. In the case of antitumor therapy, association of the therapeutic agent with a carrier system can minimize damage to healthy, non-target tissues, while limit systemic release and promoting long circulation to enhance uptake at the cancerous site due to the enhanced permeation and retention effect (EPR). Stimuli-responsive systems have become a promising way to deliver and release payloads in a site-selective manner and carrier systems have been derived from a wide variety of materials, including inorganic nanoparticles, lipids, and polymers that have been imbued with stimuli-sensitive properties to accomplish triggered release. The unique features in the tumor microenvironment can serve as an endogenous stimulus (pH, redox potential, or unique enzymatic activity) or the locus of an applied external stimulus (heat or light) to trigger the controlled release of API. Triggered release is generally based on the principle of membrane destabilization from local defects within bilayer membranes to effect release of liposome-entrapped drugs. This review focuses on the literature appearing between November 2008–February 2016 that reports new developments in stimuli-sensitive liposomal drug delivery strategies using pH change, enzyme transformation, redox reactions, and photochemical mechanisms of activation.

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Section: Ph‐responsive Liposomesmentioning

confidence: 99%

Stimuli‐responsive liposomes for drug delivery

Lee

Thompson

2017

WIREs Nanomed Nanobiotechnol

347

190

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“…They play a central role in a design of controllable compounds, molecular machinery, and intelligent materials with a variety of possible applications including drug release, new sensor techniques, or information storage and transmission . The cyclohexane‐based molecular systems have been designed as an efficient type of such switches . In particular, we used the trans ‐2‐aminocyclohexanol moiety 1 (Scheme ) to construct the conformationally controlled crown ethers and podands and the pH sensitive “flipids” for “fliposomes.” An interaction of acid with these compounds leads to protonation of the amino group and generates a strong intramolecular hydrogen bond of O⋅⋅⋅H‐N + type (in 1B ·H + on Scheme ), which stabilizes the originally unstable conformer B , thus moving the ester groups COOR at the other end of the molecule away from each other (peacock effect).…”

Section: Introductionmentioning

confidence: 99%

“…The cyclohexane‐based molecular systems have been designed as an efficient type of such switches . In particular, we used the trans ‐2‐aminocyclohexanol moiety 1 (Scheme ) to construct the conformationally controlled crown ethers and podands and the pH sensitive “flipids” for “fliposomes.” An interaction of acid with these compounds leads to protonation of the amino group and generates a strong intramolecular hydrogen bond of O⋅⋅⋅H‐N + type (in 1B ·H + on Scheme ), which stabilizes the originally unstable conformer B , thus moving the ester groups COOR at the other end of the molecule away from each other (peacock effect). This move changes dramatically their ability to interact with another molecule or ion, or to pack into lipid bilayers (depending on the nature of R).…”

Section: Introductionmentioning

confidence: 99%

Trans‐2‐Aminocyclohexanol derivatives as pH‐triggered conformational switches

Samoshin

Zheng

Liu

2017

J of Physical Organic Chem

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A series of trans-2-aminocyclohexanol derivatives have been explored as powerful conformational pH triggers. On protonation of the amino group, a conformer with equatorial position of ammonio and hydroxy groups becomes predominant because of an intramolecular hydrogen bond and electrostatic interactions. The energy of these interactions was estimated to be above 10 kJ/mol and in some models exceeded 20 kJ/mol (strong enough to twist a ring in tert-butyl derivatives). As a result of this conformational flip, all other substituents are forced to change their orientation. If the substituents are designed to perform certain geometry-dependent functions, for example, as cation chelators or as lipid tails, such acid-induced transition may be used to control the corresponding molecular properties. The pH sensitivity of conformational equilibria was explored by 1 H nuclear magnetic resonance spectroscopy (NMR), and the titration curves were used for estimation of the pK a values of protonated compounds that varied from 2.6 to 8.5 (in d 4 -methanol) depending on the structure of amino group. Thus, trans-2-aminocyclohexanols can be also used as conformational pH indicators in organic solvents.

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“…The as-synthesized cationic lipid Diosarg and helper lipid DOPE [ 27 ] were dissolved into a mixture solution of CHCl 3 /CH 3 OH ( v / v = 98/2) at predetermined amounts (molar ratios of 2:1, 1:1 and 1:2), followed by evaporation under reduced pressure to remove the organic solvents and to form a thin lipid film; then, the resulting lipid film was hydrated with distilled water in a supersonic water bath for 30 min at room temperature. Finally, the cationic Diosarg-DOPE NPs stock solutions were further diluted in pure water to prepare the solution with the final Diosarg concentration of 1.7 × 10 −3 M (for all of the Diosarg and Diosarg-DOPE NPs).…”

Section: Methodsmentioning

confidence: 99%

Cationic Nanoparticles Assembled from Natural-Based Steroid Lipid for Improved Intracellular Transport of siRNA and pDNA

et al. 2016

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Developing new functional biomaterials from biocompatible natural-based resources for gene/drug delivery has attracted increasing attention in recent years. In this work, we prepared a series of cationic nanoparticles (Diosarg-DOPE NPs) by assembly of a natural steroid diosgenin-based cationic lipid (Diosarg) with commercially-available helper lipid 1,2-dioleoyl-sn-glycero-3-phosphorethanolamine (DOPE). These cationic Diosarg-DOPE NPs were able to efficiently bind siRNA and plasmid DNA (pDNA) via electrostatic interactions to form stable, nano-sized cationic lipid nanoparticles instead of lamellar vesicles in aqueous solution. The average particle size, zeta potentials and morphologies of the siRNA and pDNA complexes of the Diosarg-DOPE NPs were examined. The in vitro cytotoxicity of NPs depends on the dose and assembly ratio of the Diosarg and DOPE. Notably, the intracellular transportation efficacy of the exogenesis siRNA and pDNA could be greatly improved by using the Diosarg-DOPE NPs as the cargoes in H1299 cell line. The results demonstrated that the self-assembled Diosarg-DOPE NPs could achieve much higher intracellular transport efficiency for siRNA or pDNA than the cationic lipid Diosarg, indicating that the synergetic effect of different functional lipid components may benefit the development of high efficiency nano-scaled gene carriers. Moreover, it could be noted that the traditional “lysosome localization” involved in the intracellular trafficking of the Diosarg and Diosarg-DOPE NPs, indicating the co-assembly of helper lipid DOPE, might not significantly affect the intracellular localization features of the cationic lipids.

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trans-2-Aminocyclohexanol-based amphiphiles as highly efficient helper lipids for gene delivery by lipoplexes

Cited by 16 publications

References 60 publications

Stimuli‐responsive liposomes for drug delivery

Stimuli‐responsive liposomes for drug delivery

Trans‐2‐Aminocyclohexanol derivatives as pH‐triggered conformational switches

Cationic Nanoparticles Assembled from Natural-Based Steroid Lipid for Improved Intracellular Transport of siRNA and pDNA

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