Fabrication of Cellulose-Nanocrystal-Based Folate Targeted Nanomedicine via Layer-by-Layer Assembly with Lysosomal pH-Controlled Drug Release into the Nucleus
| Autor: | Zhang Han, Yi Xiao, Yushu Huang, Donglei You, Jiahui Yu, Mengda Xu, Wei Lu, Na Li |
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| Rok vydání: | 2019 |
| Předmět: |
Drug
Drug Liberation Polymers and Plastics media_common.quotation_subject Bioengineering macromolecular substances 02 engineering and technology 010402 general chemistry 01 natural sciences Biomaterials chemistry.chemical_compound Drug Delivery Systems Folic Acid Cell Line Tumor Materials Chemistry Humans Polyethyleneimine Prodrugs Cellulose Cytotoxicity IC50 media_common Cell Nucleus Polyethylenimine technology industry and agriculture Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology In vitro 0104 chemical sciences Nanomedicine chemistry Doxorubicin Delayed-Action Preparations MCF-7 Cells Biophysics Nanoparticles Lysosomes 0210 nano-technology |
| Zdroj: | Biomacromolecules. 20:937-948 |
| ISSN: | 1526-4602 1525-7797 |
| Popis: | 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 β-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. |
| Databáze: | OpenAIRE |
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