Self-assembling dual component nanoparticles with endosomal escape capability

Abstract

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.

Ligand-decorated click polypeptide derived nanoparticles for targeted drug delivery applications

“…The result of sufficient amounts of endosomal escape leads to the random aggregation of the block copolymer particles outside the lysosomal vesicles (Figure 6A, Panel A, right most image and its corresponding magnification in panel B). The observed reduced accumulation and release of nanoparticles from the lysosomal vesicles is due to endosomal escape 52 , a mechanism which allows entrapped endocytic carriers within the lysosomes to be released into the cytoplasm 53 . In this case, the endosomes may have undergone buffering and osmotically induced release, or endosomal membrane leakage, due to interactions of the charged amines of the free polymer segments with the membrane.…”

Probing Endosomal Escape Using pHlexi Nanoparticles

“…The molecular weight of PDEAEMA‐ b ‐PEG was determined by NMR analysis to be ≈16 kDa. Specific synthesis details are given in Wong et al To purify the PDEAEMA polymers, the polymerization mixtures were dialyzed in PBS at pH 6 with at least six buffer exchanges. A separate portion of the crude polymer PDEAEMA was precipitated into water for 24 h in a closed system.…”

“…Materials that exhibit pH sensitivity are characterized by their ability to change their physical properties such as size, shape, hydrophobicity, and/or degradation rate upon a shift in their environment . Poly[2‐(diethylamino)ethyl methacrylate) (PDEAEMA) is a well‐known pH‐responsive polymer and has a pK a value of ≈7; this value is consistent with the pH transition from the extracellular environment to intracellular compartments, e.g., endosomes . This pK a can be tuned by using monomers with different substituents on the tertiary amine .…”

“…Recently, we reported a novel nanoparticle system based on PDEAEMA using a simple and modular one‐step assembly . Nanoprecipitation was employed to form polymeric nanoparticles composed of PDEAEMA and poly(2‐diethylamino)ethyl methacrylate)‐ b ‐poly(ethylene glycol) (PDEAEMA‐ b ‐PEG).…”

Parallel comparative studies on toxicity of quantum dots synthesized and surface engineered with different methods in vitro and in vivo

“…44,45 In this study, a large number of lysosomes is observed in the liver after being treated with the three types of QDs at the beginning. However, it was found that the lysosome production in the QDs-1-treated cell group decreases with time ( Figures 5B and S2).…”