Passive, active and endogenous organ-targeted lipid and polymer nanoparticles for delivery of genetic drugs

Abstract

Genetic drugs based on nucleic acid biomolecules are a rapidly emerging class of medicines that directly reprogramme the central dogma of biology to prevent and treat disease. However, multiple biological barriers normally impede the intracellular delivery of nucleic acids, necessitating the use of a delivery system. Lipid and polymer nanoparticles represent leading approaches for the clinical translation of genetic drugs. These systems circumnavigate biological barriers and facilitate the intracellular delivery of nucleic acids in the correct cells of the target organ using passive, active and endogenous targeting mechanisms. In this Review, we highlight the constituent materials of these advanced nanoparticles, their nucleic acid cargoes and how they journey through the body. We discuss targeting principles for liver delivery, as it is the organ most successfully targeted by intravenously administered nanoparticles to date, followed by the expansion of these concepts to extrahepatic (non-liver) delivery. Ultimately, this Review connects emerging materials and biological insights playing key roles in targeting specific organs and cells in vivo.

Engineering tumor-specific gene nanomedicine to recruit and activate T cells for enhanced immunotherapy

“…However, nanoparticles are unable to selectively deliver drugs into one specific type of organ or cell, and preferentially accumulate in liver, which hinders drug delivery to treat diseases outside the liver 52,53 . Regulating the properties of nanoparticles by passive, active and endogenous targeting mechanisms has been reported to improve the organ selectivity of drug delivery 54,55 . In addition, cell type-specific promoter-induced gene expression has been reported 56 , for example, our group used nanoparticles to deliver CD68 or HSP70 promoter-modified Cas9 plasmid to achieve macrophage-specific or light-responsive gene editing 57,58 .…”

Polymeric Micellar Systems—A Special Emphasis on “Smart” Drug Delivery

“…The body’s clearance processes pose a further obstacle to the micelle’s delivery and retention. Rapid clearance lessens the nanostructures buildup and activity at the target site, even though clearance is a crucial component of delivery for clinical usage [ 90 ]. The main organs for micelles elimination are the liver, spleen, and kidney [ 57 ].…”

Nucleus-Targeting Nanoplatform Based on Dendritic Peptide for Precise Photothermal Therapy

“…However, in order to achieve precise nuclear photothermal therapy, it is necessary to overcome the obstacles in the delivery process and successfully anchor the photothermal agent to the nucleus. Therefore, nanoplatforms must have good stability, excellent cell uptake ability, precise nucleus-targeting function, and superb photothermal conversion performance [ 12 , 13 ]. Near-infrared (NIR) indocyanine dyes show excellent performance in fluorescence imaging diagnosis and optical therapy.…”