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

Polyglyoxylamides with a pH-mediated solubility and depolymerization switch

Self-immolative polymers (SIPs) are characterized by their ability to depolymerize in response to the cleavage of a single end-cap or backbone moiety, making them attractive for numerous applications including sensors, transient plastics, and delivery vehicles. For many applications, it would be desirable to have an SIP capable of depolymerizing selectively under mildly acidic aqueous conditions. However, the poor solubility of most SIPs in water, accompanied by the competing effects of end-cap cleavage and depolymerization mechanisms, has made this a challenge. Here, we describe the development of polyglyoxylamides (PGAms) with pendent amino groups to achieve solubility switching at mildly acidic pH, which allows access of water to the end-cap and consequently depolymerization. PGAms with varying amino groups were synthesized from trityl end-capped poly(ethyl glyoxylate) (PEtG). While water-insoluble PEtG underwent no detectable depolymerization between pH 5 and 7.4 and water-soluble PGAms underwent rapid depolymerization regardless of pH in this range, a PGAm with N,N-diisopropylaminoethyl (DPAE) pendent groups underwent more rapid depolymerization at pH 5–6 compared to pH 7.4. PGAms were also incorporated into block copolymers with poly(ethylene glycol) (PEG). Nanoassemblies formed from PEG-PGAm(DPAE), swelled, disassembled, and depolymerized as the pH was lowered from 8 to 5. Copolymers lacking a solubility switch did not undergo pH-dependent disassembly or depolymerization. Overall, this work provides a new platform approach for the development of pH-sensitive SIP materials for a wide range of applications

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