title: Polymer-coated echogenic lipid nanoparticles with dual release triggers.
abstract: Although lipid nanoparticles are promising drug delivery vehicles, passive release of encapsulated contents at the target site is often slow. Herein, we report contents release from targeted, polymer-coated, echogenic lipid nanoparticles in the cell cytoplasm by redox trigger and simultaneously enhanced by diagnostic frequency ultrasound. The lipid nanoparticles were polymerized on the external leaflet using a disulfide cross-linker. In the presence of cytosolic concentrations of glutathione, the lipid nanoparticles released 76% of encapsulated contents. Plasma concentrations of glutathione failed to release the encapsulated contents. Application of 3 MHz ultrasound for 2 min simultaneously with the reducing agent enhanced the release to 96%. Folic acid conjugated, doxorubicin-loaded nanoparticles showed enhanced uptake and higher cytotoxicity in cancer cells overexpressing the folate receptor (compared to the control). With further developments, these lipid nanoparticles have the potential to be used as multimodal nanocarriers for simultaneous targeted drug delivery and ultrasound imaging.
authors: Departments of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, USA.
authors: Rahul
authors: R
authors: Nahire
authors: Manas K
authors: MK
authors: Haldar
authors: Shirshendu
authors: S
authors: Paul
authors: Anaas
authors: A
authors: Mergoum
authors: Avinash H
authors: AH
authors: Ambre
authors: Kalpana S
authors: KS
authors: Katti
authors: Kara N
authors: KN
authors: Gange
authors: D K
authors: DK
authors: Srivastava
authors: Kausik
authors: K
authors: Sarkar
authors: Sanku
authors: S
authors: Mallik
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry* / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005492:Folic Acid / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D061986:MCF-7 Cells; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry
chemical_list: D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D008055:Lipids; D011108:Polymers; D004317:Doxorubicin; D005492:Folic Acid
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