The use of block copolymers to systematically modify photochromic behavior

Reversible addition fragmentation chain transfer (RAFT) living radical polymerization has been utilized successfully to allow the systematic tuning of photochromic switching rates in a rigid, ophthalmic quality, polymer matrix. Block copolymers of poly(styrene) and poly(n-butyl acrylate) were synthesized using a RAFT functionalized photochromic (spirooxazine) dye. Thus the photochromic dye initiated the polymerizations and allowed the known and precise placement of the dye at the start of the block copolymer chains. The photophysical investigation of these more complex architectures demonstrated that systematic tuning of photochromic rates could be achieved by changing the length and choice of either block. The photochromic rates were significantly more sensitive to the presence of low glass-transition temperature poly(n-butyl acrylate) than high glass-transition temperature poly(styrene), even if the poly(n-butyl acrylate) was the more distant second block from the spirooxazine

Controlling endosomal escape using nanoparticle composition:Current progress and future perspectives

Polymer nanoparticles offer significant benefits for improving delivery of biological therapeutics such as DNA and proteins, as they allow the cargo to be protected until it is delivered to a target cell. However, there are still challenges with achieving efficient delivery to the optimal cellular region. One significant roadblock is escape of nanoparticles from within the endosomal/lysosomal compartments into the cytosol. Here, we review the recent advances in understanding endosomal escape of polymer nanoparticles. We also discuss the current progress on investigating how nanoparticle structure can control endosomal escape. It is important to understand the fundamental biological processes that govern endosomal escape in order to design more effective therapeutic delivery systems.</p

pH-Responsive Polymer Nanoparticles for Drug Delivery

Stimuli-responsive nanoparticles have the potential to improve the delivery of therapeutics to a specific cell or region within the body. There are many stimuli that have shown potential for specific release of cargo, including variation of pH, redox potential, or the presence of enzymes. pH variation has generated significant interest for the synthesis of stimuli-responsive nanoparticles because nanoparticles are internalized into cells via vesicles that are acidified. Additionally, the tumor microenvironment is known to have a lower pH than the surrounding tissue. In this review, different strategies to design pH-responsive nanoparticles are discussed, focusing on the use of charge-shifting polymers, acid labile linkages, and crosslinking

Controlling Endosomal Escape Using pH-Responsive Nanoparticles with Tunable Disassembly

© 2018 American Chemical Society. Endosomal escape is a bottleneck in the efficient delivery of therapeutics using nanoparticles; therefore understanding how this property can be optimized is important for achieving better therapeutic outcomes. It has been demonstrated that pH-responsive nanoparticles (pHlexi nanoparticles) have potential to achieve effective escape from the endosomal compartments of the cell. In this paper a library of five pHlexi particles with tunable disassembly pH were synthesized by combining poly(ethylene glycol)-b-poly(2-(diethylamino)ethyl methacrylate) (PEG-b-PDEAEMA) with random copolymers of 2-(diethylamino)ethyl methacrylate and 2-(diisopropylamino)ethyl methacrylate. A series of cellular studies were conducted to investigate the effect of particle composition on in vitro behavior. Endosomal escape was probed using a calcein escape assay in NIH/3T3 fibroblast cells, demonstrating endosomal escape increased with increasing particle concentration. Interestingly, it was shown that endosomal escape was most efficient with particles that disassemble at high (pH 7.2) or low (pH 4.9) pH, with particles that disassemble between pH 5.8 and 6.6 inducing decreased levels of endosomal escape. This change in endosomal escape behavior suggests particles can induce escape by different pathways. The results show that tuning the core component of pHlexi particles can improve the effectiveness of endosomal escape capabilities and thus their ability to act as effective delivery systems