Effects of lipid nanoparticles on physicochemical properties, cellular uptake, and lymphatic uptake of 6-methoxflavone

COVID-19 vaccines have been developed with unprecedented speed which would not have been possible without decades of fundamental research on delivery nanotechnology. Lipid-based nanoparticles have played a pivotal role in the successes of COVID-19 vaccines and many other nanomedicines, such as Doxil® and Onpattro®, and have therefore been considered as the frontrunner in nanoscale drug delivery systems. In this review, we aim to highlight the progress in the development of these lipid nanoparticles for various applications, ranging from cancer nanomedicines to COVID-19 vaccines. The lipid-based nanoparticles discussed in this review are liposomes, niosomes, transfersomes, solid lipid nanoparticles, and nanostructured lipid carriers. We particularly focus on the innovations that have obtained regulatory approval or that are in clinical trials. We also discuss the physicochemical properties required for specific applications, highlight the differences in requirements for the delivery of different cargos, and introduce current challenges that need further development. This review serves as a useful guideline for designing new lipid nanoparticles for both preventative and therapeutic vaccines including immunotherapies.

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Engineered ionizable lipid nanoparticles for targeted delivery of RNA therapeutics into different types of cells in the liver

Science Advances ◽

10.1126/sciadv.abf4398 ◽

2021 ◽

Vol 7 (9) ◽

pp. eabf4398

Author(s):

M. Kim ◽

M. Jeong ◽

S. Hur ◽

Y. Cho ◽

J. Park ◽

...

Keyword(s):

Cellular Uptake ◽

Targeted Delivery ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipid Nanoparticles ◽

Liver Sinusoidal Endothelial Cells ◽

Main Challenge ◽

Cell Type Specific ◽

Selective Delivery

Ionizable lipid nanoparticles (LNPs) have been widely used for in vivo delivery of RNA therapeutics into the liver. However, a main challenge remains to develop LNP formulations for selective delivery of RNA into certain types of liver cells, such as hepatocytes and liver sinusoidal endothelial cells (LSECs). Here, we report the engineered LNPs for the targeted delivery of RNA into hepatocytes and LSECs. The effects of particle size and polyethylene glycol–lipid content in the LNPs were evaluated for the hepatocyte-specific delivery of mRNA by ApoE-mediated cellular uptake through low-density lipoprotein receptors. Targeted delivery of RNA to LSECs was further investigated using active ligands. Incorporation of mannose allowed the selective delivery of RNA to LSECs, while minimizing the unwanted cellular uptake by hepatocytes. These results demonstrate that engineered LNPs have great potential for the cell type–specific delivery of RNA into the liver and other tissues.

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Peptide-nucleic acid nanostructures for transfection

BioMolecular Concepts ◽

10.1515/bmc-2011-0067 ◽

2012 ◽

Vol 3 (3) ◽

pp. 283-293 ◽

Cited By ~ 1

Author(s):

Burkhard Bechinger

Keyword(s):

Nucleic Acid ◽

Physicochemical Properties ◽

Cellular Uptake ◽

Peptide Nucleic Acid ◽

Endosomal Escape ◽

Medical Applications ◽

Specific Cell ◽

Charge Composition ◽

Cell Surfaces ◽

Intracellular Targeting

AbstractTo use nucleic acids in biomedical research and medical applications, these highly hydrophilic macromolecules have to be transported through the organism, targeted to specific cell surfaces, and have to cross cellular barriers. To this end, nanosized transfection complexes have been designed and several of them have been successfully tested. Here, the different steps of the transfection process and the particular optimization protocols are reviewed, including the physicochemical properties of such vectors (size, charge, composition), protection in serum, cellular uptake, endosomal escape, and intracellular targeting. The transfection process has been subdivided into separate steps and here special emphasis is given to peptides that have been designed to optimize these steps individually. Finally, complex devices encompassing a multitude of beneficial functionalities for transfection have been developed.

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