Fabrication of Cellulose-Nanocrystal-Based Folate Targeted Nanomedicine via Layer-by-Layer Assembly with Lysosomal pH-Controlled Drug Release into the Nucleus
- 8 January 2019
- journal article
- research article
- Published by American Chemical Society (ACS) in Biomacromolecules
- Vol. 20 (2), 937-948
- https://doi.org/10.1021/acs.biomac.8b01556
Abstract
To increase the cellular uptake and drug loading of cellulose nanocrystal (CNC)-based nanomedicines, folate/cis[email protected]@CNC (FA/[email protected]@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/[email protected]@CNC hybrids was 11.3 wt %, which was almost 20-fold higher than that of the CNC-based nano-prodrug we reported previously. FA/[email protected]@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/[email protected]@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/[email protected]@CNC hybrid nanomedicines displayed efficient targetability and enhanced cellular uptake. In addition, FA/[email protected]@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/[email protected]@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.Keywords
Funding Information
- National Natural Science Foundation of China (81871405, 51573050)
This publication has 53 references indexed in Scilit:
- Fluorescent Labeling and Characterization of Cellulose Nanocrystals with Varying Charge ContentsBiomacromolecules, 2013
- Nanocellulose: a new ageless bionanomaterialMaterials Today, 2013
- Responsive layer-by-layer materials for drug deliveryJournal of Controlled Release, 2012
- Fluorescent Nanorods and Nanospheres for Real‐Time In Vivo Probing of Nanoparticle Shape‐Dependent Tumor PenetrationAngewandte Chemie, 2011
- Immunotoxins and Anticancer Drug Conjugate Assemblies: The Role of the Linkage between ComponentsToxins, 2011
- Polymer Nanoneedle‐Mediated Intracellular Drug DeliverySmall, 2011
- Effect of Surface Charge on the Cellular Uptake and Cytotoxicity of Fluorescent Labeled Cellulose NanocrystalsACS Applied Materials & Interfaces, 2010
- Flexible Filaments for in Vivo Imaging and Delivery: Persistent Circulation of Filomicelles Opens the Dosage Window for Sustained Tumor ShrinkageMolecular Pharmaceutics, 2009
- The effect of particle design on cellular internalization pathwaysProceedings of the National Academy of Sciences of the United States of America, 2008
- Magnetic Iron Oxide Nanoworms for Tumor Targeting and ImagingAdvanced Materials, 2008