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.

Electrochemistry-Induced Improvements of Mechanical Strength, Self-Healing, and Interfacial Adhesion of Hydrogels.

Hydrogels have demonstrated great potential in biomedical and engineering areas. To improve the physical performance, development of efficient physical/chemical protocols is essential. Herein, an electrochemistry functionalization strategy that is capable of enabling the functional improvements of hydrogel is reported. The electrochemistry functionalization is demonstrated on a hydrogel model of polyacrylamide (PAAm)@κ-carrageenan. The electrochemistry reaction generates metal ions (Fe3+ ) that migrate and coordinate with the sulfate groups of κ-carrageenan resulting in the prominent function improvements. In comparison with untreated PAAm@κ-carrageenan hydrogel, it can improve the mechanical strength by 7.37 times, and can increase the interfacial adhesion energy of the hydrogel on a glass surface from 0 to 1400 J m-2 , stronger than the bonding strength of tendons (adhesion energy: ≈800 J m-2 ). Two pieces of hydrogel strips integrate into an intact structure by the electrochemistry functionalization, where the healing efficiency reaches 100% in comparison to the untreated hydrogel. The most significant development is that it enables functional patterning on the hydrogel by the electrode assembly, which provides the hydrogel with modular sensitivity to external pressure. Therefore, it can be a general protocol for rapid generation of multifunctional hydrogels for biomedical and engineering developments.