Biocompatible crosslinked β-cyclodextrin nanoparticles as multifunctional carriers for cellular delivery

Abstract

Nanoparticle-based biomedicine has received enormous attention for theranostic applications, as these systems are expected to overcome several drawbacks of conventional therapy. Herein, effective and controlled drug delivery systems with on-demand release abilities and biocompatible properties are used as a versatile and powerful class of nanocarriers. We report the synthesis of a novel biocompatible and multifunctional material, entirely consisting of covalently crosslinked organic molecules. Specifically, β-cyclodextrin (CD) precursors were crosslinked with rigid organic linker molecules to obtain small (∼150 nm), thermally stable and highly water-dispersible nanoparticles with an accessible pore system containing β-CD rings. The nanoparticles can be covalently labeled with dye molecules to allow effective tracking in in vitro cell experiments. Rapid sugar-mediated cell-uptake kinetics were observed with HeLa cells, revealing exceptional particle uptake within only 30 minutes. Additionally, the particles could be loaded with different cargo molecules showing pH-responsive release behavior. Successful nuclei staining with Hoechst 33342 dye and effective cell killing with doxorubicin cargo molecules were demonstrated in live-cell experiments, respectively. This novel nanocarrier concept provides a promising platform for the development of controllable and highly biocompatible theranostic systems.

Cyclodextrin Based Nanoparticles for Drug Delivery and Theranostics

“…[143][144][145] Table 4. [149][150][151][152][153][154][155][156][157][158][159][160][161][162][163]…”

<p>Manganese dioxide nanosheets: from preparation to biomedical applications</p>

“…The controlled drug delivery systems (c-DDSs) for current medications have received increasing interest from numerous chemists and clinical physicians owing to their low toxicities, broad therapeutic windows and ideal administrational efficacies compared with conventional DDSs 117–121. On-demand DDSs triggered by intrinsic physiological microenvironment changes (eg, pH,122 redox agents,123,124 enzymes,125 and heat126,127) and/or external artificially introduced stimuli128,129 (eg, light,130 laser pulses,131 magnetic/electronic fields,132 and ultrasonication133) can simultaneously diminish the side-effects of anticancer agents toward normal tissue to improve the therapeutic effects. Previous reports on DDSs have mainly focused on nanocomposites, such as magnetic composites and upconversion nanoparticles, and most of them have been magnetically functionalized mesoporous materials or hollow spherical particles with the drugs being released via changes in the pH or temperature 121,134–137.…”

Efficient Grafting of Cyclodextrin to Alginate and Performance of the Hydrogel for Release of Model Drug

“…Furthermore, by forming inclusion complexes, CyDs protect drugs from being prematurely degraded and metabolized 17 . CyDs are in general considered as biocompatible in relation to their participation as functional elements in materials and devices intended for medical uses as exemplified by recent publications 18–20 . Cyclodextrins have even shown to improve the biocompatibility of e.g.…”