Scaling the effect of hydrophobic chain length on gene transfer properties of di-alkyl, di-hydroxy ethylammonium chloride based cationic amphiphiles

Hiwale, Ankita A.; Voshavar, Chandrashekhar; Dharmalingam, Priya; Dhayani, Ashish; Mukthavaram, Rajesh; Nadella, Rasajna; Sunnapu, Omprakash; Naidu, V.G.M.; Chaudhuri, Arabinda; Marepally, Srujan; Vemula, Praveen Kumar

doi:10.1039/c7ra02271a

Cited by 14 publications

(13 citation statements)

References 29 publications

(41 reference statements)

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“…Liposomes are composed of DODEAC (N,N-di-n-octadecyl-N,N-dihydroxyethylammonium chloride), a well-known cationic lipid, and prepared by the injection method. 20,21 MVs were collected from the MCF-7 cell media using differential centrifugation. The fusion process was validated via a FRET-based lipid-mixing assay (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

“…There are similar reports available in the literature on hybrid-vesicle preparation by fusing EVs with synthetic liposomes with PEG. , Importantly, in this work, the mechanical aspects of these hybrid vesicles in various PEG% are determined by a FRET-based lipid-mixing assay, which is a completely new feature and has an impact on the hybrid vesicle’s delivery efficacy. Earlier we showed that asymmetric lipid-based vesicles are promising carriers, and their delivery efficiency depends on the structural flexibility/rigidity balance. − Taking note of these factors, to improve the delivery efficacy of a synthetic liposome further, in this work we fused asymmetric liposomes with MVs (derived from breast cancer MCF-7 cells) with polyethylene glycol (PEG) as a fusogenic agent and developed a hybrid vesicle system. We validated hybrid-vesicle formation with FRET and flow cytometry-based analysis and used them for model siRNA (Alexa647 tagged) delivery into MCF-7 cells to check the performances of these newly developed carriers.…”

Section: Introductionmentioning

confidence: 99%

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Polyethylene Glycol-Mediated Fusion of Extracellular Vesicles with Cationic Liposomes for the Design of Hybrid Delivery Systems

Mukherjee

Paul

Sarker

et al. 2021

ACS Appl. Bio Mater.

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To realize a customizable biogenic delivery platform, herein we propose combining cell-derived extracellular vesicles (EVs) derived from breast cancer cell line MCF-7 with synthetic cationic liposomes using a fusogenic agent, polyethylene glycol (PEG). We performed a fluorescence resonance energy transfer (FRET)-based lipid-mixing assay with varying PEG 1000 concentrations (0%, 15%, and 30%) correlated with flow cytometry-based analysis and supported by dimensional analysis by dynamic light scattering (DLS), transmission electron microscopy (TEM), and atomic force microscopy (AFM) to validate our fusion strategy. Our data revealed that these hybrid vesicles at a particular concentration of PEG (∼15%) improved the cellular delivery efficiency of a model siRNA molecule to the EV parental breast cancer cells, MCF-7, by factors of 2 and 4 compared to the loaded liposome and EV precursors, respectively. The critical rigidity/pliability balance of the hybrid systems fused by PEG seems to be playing a pivotal role in improving their delivery capability. This approach can provide clinically viable delivery solutions using EVs.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polyethylene Glycol-Mediated Fusion of Extracellular Vesicles with Cationic Liposomes for the Design of Hybrid Delivery Systems

Mukherjee

Paul

Sarker

et al. 2021

ACS Appl. Bio Mater.

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“…Moreover, it has been shown that the symmetry of the two alkyl chains bound to the headgroup plays some role in the behavior of two-tailed cationic lipids (Chandrashekhar et al, 2011;Hiwale et al, 2017;Le Corre et al, 2014;Wang and Macdonald, 2004). SAR studies revealed that the degree of asymmetry between the two tails strongly impacts the phase behavior of the resulting lipid as a consequence of the differences in the overall tail free volume (Zhang et al, 2011).…”

Section: Aliphatic Chainsmentioning

confidence: 99%

Cationic lipids for gene delivery: many players, one goal

Ponti

Campolungo

Melchiori

et al. 2021

Chemistry and Physics of Lipids

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Lipid-based carriers represent the most widely used alternative to viral vectors for gene expression and gene silencing purposes. This class of non-viral vectors is particularly attractive for their ease of synthesis and chemical modifications to endow them with desirable properties. Despite combinatorial approaches have led to the generation of a large number of cationic lipids displaying different supramolecular structures and improved behavior, additional efforts are needed towards the development of more and more effective cationic lipids for transfection purposes. With this review, we seek to highlight the great progress made in the design of each and every constituent domain of cationic lipids, that is, the chemical structure of the headgroup, linker and hydrophobic moieties, and on the specific effect on the assembly with nucleic acids. Since the complexity of such systems is known to affect their performances, the role of formulation, stability and phase behavior on the transfection efficiency of such assemblies will be thoroughly discussed. Our objective is to provide a conceptual framework for the development of ever more performing lipid gene delivery vectors. Highlights: Progress in the rational design of cationic lipids  Outlook on the influence of cationic lipid domains on nucleic acids complexation and delivery  Outlook on the influence of cationic lipid composition on its ultimate geometry and supramolecular structures of lipoplexes Abbreviations:

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“…The CA structure significantly affects the efficiency of NA delivery to eukaryotic cells. In recent years, many monocationic amphiphiles have been obtained [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ] that form liposomes for NA delivery. In this review, we will consider polycationic amphiphiles, which, compared to monocationic analogs, enable the more efficient transport of NAs into cells due to the formation of a system of distributed charges in the polyamine matrix and their ability to facilitate NA release from endosomes.…”

Section: Introductionmentioning

confidence: 99%

Lipophilic Polyamines as Promising Components of Liposomal Gene Delivery Systems

Puchkov

Маслов

2021

Pharmaceutics

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Gene therapy requires an effective and safe delivery vehicle for nucleic acids. In the case of non-viral vehicles, including cationic liposomes, the structure of compounds composing them determines the efficiency a lot. Currently, cationic amphiphiles are the most frequently used compounds in liposomal formulations. In their structure, which is a combination of hydrophobic and cationic domains and includes spacer groups, each component contributes to the resulting delivery efficiency. This review focuses on polycationic and disulfide amphiphiles as prospective cationic amphiphiles for gene therapy and includes a discussion of the mutual influence of structural components.

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Scaling the effect of hydrophobic chain length on gene transfer properties of di-alkyl, di-hydroxy ethylammonium chloride based cationic amphiphiles

Abstract: Asymmetric hydrocarbon chains influence the efficiency of cationic lipids based liposomes in nucleic acid delivery. A systematic investigation of role of asymmetry in transfection efficiency.

Cited by 14 publications

References 29 publications

Polyethylene Glycol-Mediated Fusion of Extracellular Vesicles with Cationic Liposomes for the Design of Hybrid Delivery Systems

Polyethylene Glycol-Mediated Fusion of Extracellular Vesicles with Cationic Liposomes for the Design of Hybrid Delivery Systems

Cationic lipids for gene delivery: many players, one goal

Lipophilic Polyamines as Promising Components of Liposomal Gene Delivery Systems

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