Self-assembling dual component nanoparticles with endosomal escape capability.
This study reports a novel nanoparticle system with simple and modular one-step assembly, which can respond intelligently to biologically relevant variations in pH. Importantly, these particles also show the ability to induce escape from the endosomal/lysosomal compartments of the cell, which is integral to the design of efficient polymeric delivery systems. The nanoparticles were formed by the nanoprecipitation of pH-responsive poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) and poly(2-(diethylamino)ethyl methacrylate)-b-poly(ethylene glycol) (PDEAEMA-b-PEG). Rhodamine B octadecyl ester perchlorate was successfully encapsulated within the hydrophobic core of the nanoparticle upon nanoprecipitation into PBS at pH 8. These particles disassembled when the pH was reduced below 6.8 at 37 °C. Cellular experiments showed the successful uptake of the nanoparticles into the endosomal/lysosomal compartments of 3T3 fibroblast cells. The ability to induce escape from the endosomes was demonstrated by the use of calcein, a membrane-impermeable fluorophore. The modular nature of these particles combined with promising endosomal escape capabilities make these dual component PDEAEMA nanoparticles useful for drug and gene delivery applications.
Department of Chemistry, The University of Melbourne, Parkville, Victoria 3010, Australia. gsuch@unimelb.edu.au.
Adelene S M
AS
Wong
Sarah K
SK
Mann
Ewa
E
Czuba
Audrey
A
Sahut
Haiyin
H
Liu
Tiffany C
TC
Suekama
Tayla
T
Bickerton
Angus P R
AP
Johnston
Georgina K
GK
Such
D016475:3T3 Cells; D000818:Animals; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D011992:Endosomes / Q000378:metabolism; D004952:Esters; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008689:Methacrylates / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009757:Nylons / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D012235:Rhodamines / Q000008:administration & dosage / Q000737:chemistry
D004337:Drug Carriers; D004952:Esters; D005456:Fluorescent Dyes; D008689:Methacrylates; D009757:Nylons; D012235:Rhodamines; C425723:octadecylrhodamine B; C109846:poly(2-(diethylamino)ethyl methacrylate); D011092:Polyethylene Glycols