Cover Picture: Switchable Lipids: Conformational Change for Fast pH‐Triggered Cytoplasmic Delivery (Angew. Chem. Int. Ed. 43/2015)

Viricel, Warren; Mbarek, Amira; Leblond, Jeanne

doi:10.1002/anie.201507428

Cited by 3 publications

(11 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another class of pH‐sensitive siRNA lipid carriers are cationic switchable lipids (CSL), whereby protonation induces a conformational change that allows endosomal escape and siRNA release. [ 121,122 ] These CSLs contain a tricyclic pH‐sensitive head group which can be modified with various ionizable amino groups at the 4′‐position of the central pyridine ring ( Figure A). These lipids are able to change their conformation upon protonation at endosomal pH values (Figure 8B).…”

Section: Environment‐sensitive Lipids For Efficient Sirna Deliverymentioning

confidence: 99%

“…CSLs with two lipid chains of 10–13 carbons, especially alkyl chains of 12 carbons, have demonstrated the best efficacy for in vivo siRNA delivery. [ 121,122 ] Different headgroups of double‐dimethylamine (CSL1), mono primary amine (CSL2) and mono dimethylamine (CSL3) have also been tested. Mono‐substituted CSL2 and CSL3 lipids and their siRNA nanoparticles showed dose‐dependent knockdown whereas CSL1 was ineffective.…”

Section: Environment‐sensitive Lipids For Efficient Sirna Deliverymentioning

confidence: 99%

“…Additionally, CSLs did not cause any notable cytotoxicity and hemolytic activity under the evaluated conditions. [ 121 ]…”

Section: Environment‐sensitive Lipids For Efficient Sirna Deliverymentioning

confidence: 99%

“…The lipid CSL3 demonstrated potent silencing ability at low siRNA doses with efficient endosomal escape, whereas its nonswitchable analog molecule, CSL4, remained in endosomes due to its inability to undergo a pH‐sensitive conformational change ( Figure A). [ 121 ] Nanoparticles were shown to be stable in PBS solution for more than one week, a critical property for clinical translation. [ 121 ] In mouse models of liver carcinoma, the CSL3 formulation containing siRNA to PCSK9 exhibited near‐complete knockdown of tumoral PCSK9 and pro‐PCSK9 proteins, demonstrating efficient in vivo siRNA delivery (Figure 9B).…”

Section: Environment‐sensitive Lipids For Efficient Sirna Deliverymentioning

confidence: 99%

“…[ 121 ] Nanoparticles were shown to be stable in PBS solution for more than one week, a critical property for clinical translation. [ 121 ] In mouse models of liver carcinoma, the CSL3 formulation containing siRNA to PCSK9 exhibited near‐complete knockdown of tumoral PCSK9 and pro‐PCSK9 proteins, demonstrating efficient in vivo siRNA delivery (Figure 9B). [ 121 ] In addition, an ex vivo biodistribution study was performed using CSL3‐delivered fluorescently labeled siRNA, displaying substantial uptake of CSL3 nanoparticles in the liver, with additional strong uptake in the kidneys (Figure 9C).…”

Section: Environment‐sensitive Lipids For Efficient Sirna Deliverymentioning

confidence: 99%

See 4 more Smart Citations

Environment‐Responsive Lipid/siRNA Nanoparticles for Cancer Therapy

Lü

Laney

Hall

et al. 2020

Adv Healthcare Materials

View full text Add to dashboard Cite

RNA interference (RNAi) is a promising technology to regulate oncogenes for treating cancer. The primary limitation of siRNA for clinical application is the safe and efficacious delivery of therapeutic siRNA into target cells. Lipid‐based delivery systems are developed to protect siRNA during the delivery process and to facilitate intracellular uptake. There is a significant progress in lipid nanoparticle systems that utilize cationic and protonatable amino lipid systems to deliver siRNA to tumors. Among these lipids, environment‐responsive lipids are a class of novel lipid delivery systems that are capable of responding to the environment changes during the delivery process and demonstrate great promise for clinical translation for siRNA therapeutics. Protonatable or ionizable amino lipids and switchable lipids as well as pH‐sensitive multifunctional amino lipids are the presentative environment‐responsive lipids for siRNA delivery. These lipids are able to respond to environmental changes during the delivery process to facilitate efficient cytosolic siRNA delivery. Environment‐responsive lipid/siRNA nanoparticles (ERLNP) are developed with the lipids and are tested for efficient delivery of therapeutic siRNA into the cytoplasm of cancer cells to silence target genes for cancer treatment in preclinical development. This review summarizes the recent developments in environment‐response lipids and nanoparticles for siRNA delivery in cancer therapy.

show abstract

Section: Environment‐sensitive Lipids For Efficient Sirna Deliverymentioning

confidence: 99%

Section: Environment‐sensitive Lipids For Efficient Sirna Deliverymentioning

confidence: 99%

“…Additionally, CSLs did not cause any notable cytotoxicity and hemolytic activity under the evaluated conditions. [ 121 ]…”

Section: Environment‐sensitive Lipids For Efficient Sirna Deliverymentioning

confidence: 99%

Section: Environment‐sensitive Lipids For Efficient Sirna Deliverymentioning

confidence: 99%

Section: Environment‐sensitive Lipids For Efficient Sirna Deliverymentioning

confidence: 99%

See 3 more Smart Citations

Environment‐Responsive Lipid/siRNA Nanoparticles for Cancer Therapy

Lü

Laney

Hall

et al. 2020

Adv Healthcare Materials

View full text Add to dashboard Cite

show abstract

pH‐Cleavable Nucleoside Lipids: A New Paradigm for Controlling the Stability of Lipid‐Based Delivery Systems

et al. 2015

View full text Add to dashboard Cite

Lipid-based delivery systems are an established technology with considerable clinical acceptance and several applications in human. Herein, we report the design, synthesis and evaluation of novel orthoester nucleoside lipids (ONLs) for the modulation of liposome stability. The ONLs contain head groups with 3'-orthoester nucleoside derivatives featuring positive or negative charges. The insertion of the orthoester function in the NL structures allows the formation of pH-sensitive liposomes. ONL-based liposomes can be hydrolyzed to provide nontoxic products, including nucleoside derivatives and hexadecanol. To allow the release to be tunable at different hydrolysis rates, the charge of the polar head structure is modulated, and the head group can be released at a biologically relevant pH. Crucially, when ONLs are mixed with natural phosphocholine lipids (PC), the resultant liposome evolves toward the formation of a hexadecanol/PC lamellar system. Biological evaluation shows that stable nucleic acid lipid particles (SNALPs) formulated with ONLs and siRNAs can effectively enter into tumor cells and release their nucleic acid payload in response to an intracellular acidic environment. This results in a much higher antitumor activity than conventional SNALPs. The ability to use pH-cleavable nucleolipids to control the stability of lipid-based delivery systems represents a promising approach for the intracellular delivery of drug cargos.

show abstract

Tracking the Endosomal Escape: A Closer Look at Calcein and Related Reporters

Hausig‐Punke

Richter

Hoernke

et al. 2022

Macromolecular Bioscience

View full text Add to dashboard Cite

Crossing the cellular membrane and delivering active pharmaceuticals or biologicals into the cytosol of cells is an essential step in the development of nanomedicines. One of the most important intracellular processes regarding the cellular uptake of biologicals is the endolysosomal pathway. Sophisticated nanocarriers are developed to overcome a major hurdle, the endosomal entrapment, and delivering their cargo to the required site of action. In parallel, in vitro assays are established analyzing the performance of these nanocarriers. Among them, the release of the membrane‐impermeable dye calcein has become a popular and straightforward method. It is accessible for most researchers worldwide, allows for rapid conclusions about the release potential, and enables the study of release mechanisms. This review is intended to provide an overview and guidance for scientists applying the calcein release assay. It comprises a survey of several applications in the study of endosomal escape, considerations of potential pitfalls, challenges, and limitations of the assay, and a brief summary of complementary methods. Based on this review, it is hoped to encourage further research groups to take advantage of the calcein release assay for their own purposes and help to create a database for more efficient cross‐correlations between nanocarriers.

show abstract

Cover Picture: Switchable Lipids: Conformational Change for Fast pH‐Triggered Cytoplasmic Delivery (Angew. Chem. Int. Ed. 43/2015)

Cited by 3 publications

References 0 publications

Environment‐Responsive Lipid/siRNA Nanoparticles for Cancer Therapy

Environment‐Responsive Lipid/siRNA Nanoparticles for Cancer Therapy

pH‐Cleavable Nucleoside Lipids: A New Paradigm for Controlling the Stability of Lipid‐Based Delivery Systems

Tracking the Endosomal Escape: A Closer Look at Calcein and Related Reporters

Contact Info

Product

Resources

About