Ion conduction in the comb-branched polyether electrolytes with controlled network structures.

Solid polymer electrolytes (SPEs) based on centipede-like polyethers composed of short ethylene oxide (EO) brushes and allyl functional groups were generated and followed by in situ crosslinking via thiol-ene "click" chemistry. The delicate control of the mesh sizes of the networks was achieved by tuning the composition of the backbone and the length of the bi-functional EO crosslinkers, which was further evaluated by the equilibrium swelling experiments and the Flory-Rehner theory. This type of SPE demonstrates good compatibility with lithium anodes and a high ionic conductivity up to 1.6 × 10-4 S cm-1 at room temperature, 2 orders of magnitude higher than that of the typical linear PEO. The temperature dependence of the ionic conductivity can be described by the Vogel-Tammann-Fulcher (VTF) equation, which shows a systematic variation of the ion conduction behaviors with the network structures. Particularly, the increase of mesh size results in the increase of the conductivity and the decrease in the content of ion pairs, which is verified in the networks based on end-functionalized systems as well. The higher free ion content in the loose network has been attributed to its larger conformational freedom and optimized complexation of the lithium ions. This type of comb-branched polyether with solvent-like oligomer EO brushes also shows the potential to alleviate the compensation effect between the apparent activation energy and the ion carrier contents, which may provide a promising platform to fabricate high performance electrolytes with optimized ionic conductivity.

Rod-Shaped Micelles Based on PHF- g-(PCL-PEG) with pH-Triggered Doxorubicin Release and Enhanced Cellular Uptake.

A biodegradable brush-type copolymer PHF- g-(PCL-PEG) based on a cleavable polyacetal backbone and biodegradable side chain modified with polyethylene glycol (PEG) was synthesized in this paper. This particular structure was directional to facilitate the formation of spherical or rod-shaped micelles. Flow cytometry showed that rod-shaped micelles displayed enhanced cellular uptake compared to spherical micelles. Rod-shaped micelles were selected to investigate their drug delivery abilities in detail. In vitro experiments verified the pH-triggered drug release of DOX-loaded micelles, and the release rate of doxorubicin (DOX) was 77% at pH 5.0 and 26% at pH 7.4. In drug-release kinetic analysis, a double-exponential model achieved the best fit. The copolymer appeared to be almost nontoxic, while the DOX-loaded micelles showed equivalent cytotoxicity compared to DOX at high concentration. The endocytosis of DOX-loaded micelles was two times that of DOX. Our findings suggest that the pH-sensitive brush type copolymer could be a possible carrier in drug delivery.

Fabrication of Cellulose-Nanocrystal-Based Folate Targeted Nanomedicine via Layer-by-Layer Assembly with Lysosomal pH-Controlled Drug Release into the Nucleus.

To increase the cellular uptake and drug loading of cellulose nanocrystal (CNC)-based nanomedicines, folate/ cis-aconityl-doxorubicin@polyethylenimine@CNC (FA/CAD@PEI@CNC) nanomedicines were built up by the building blocks of folate (FA), cis-aconityl-doxorubicin (CAD), polyethylenimine (PEI), and CNCs via the robust layer-by-layer (LbL) assembly technique. The drug loading content (DLC) of FA/CAD@PEI@CNC hybrids was 11.3 wt %, which was almost 20-fold higher than that of the CNC-based nano-prodrug we reported previously. FA/CAD@PEI@CNC nanomedicines showed lysosomal pH-controlled drug release profiles over 24 h. In detail, the cumulative drug release was over 95% at pH 5.5, while the cumulative drug release was only 17% at pH 7.4. In vitro, FA/CAD@PEI@CNC hybrid nanomedicines had a higher (9.7-fold) mean fluorescent intensity (MFI) than that of DOX·HCl, with enhanced cytotoxicity and decreased IC50 against MCF-7. Thus, FA/CAD@PEI@CNC hybrid nanomedicines displayed efficient targetability and enhanced cellular uptake. In addition, FA/CAD@PEI@CNC nanomedicine could deliver more DOX to the nucleus than the control group, due to the ß-carboxylic acid catalyzed breakage of the pH-labile cis-aconityl amide linkages in CAD. These results indicated that FA/CAD@PEI@CNC nanomedicines achieved lysosomal pH-controlled drug release into the nucleus and showed great potential to be high-performance nanomedicines to improve the delivery efficiency and therapy efficacy. This study for CNC-based nanomedicines provided important insights into the bioapplication of CNCs modified by LbL assembly.