Tailored design of NHS-SS-NHS cross-linked chitosan nano-hydrogels for enhanced anti-tumor efficacy by GSH-responsive drug release.

The traditional chemotherapeutic agents' disadvantages such as high toxicity, untargeting and poor water solubility lead to disappointing chemotherapy effects, which restricts its clinical application. In this work, novel size-appropriate and glutathione (GSH)-responsive nano-hydrogels were successfully prepared via the active ester method between chitosan (containing -NH2) and cross-linker (containing NHS). Especially, the cross-linker was elaborately designed to possess a disulfide linkage (SS) as well as two terminal NHS groups, namely NHS-SS-NHS. These functionalities endowed chitosan-based cross-linked scaffolds with capabilities for drug loading and delivery, as well as a GSH-responsive mechanism for drug release. The prepared nano-hydrogels demonstrated excellent performance applicable morphology, excellent drug loading efficiency (∼22.5%), suitable size (∼100 nm) and long-term stability. The prepared nano-hydrogels released over 80% doxorubicin (DOX) after incubation in 10 mM GSH while a minimal DOX release less than 25% was tested in normal physiological buffer (pH = 7.4). The unloaded nano-hydrogels did not show any apparent cytotoxicity to A 549 cells. In contrast, DOX-loaded nano-hydrogels exhibited marked anti-tumor activity against A 549 cells, especially in high GSH environment. Finally, through fluorescent imaging and flow cytometry analysis, fluorescein isothiocyanate-labeled nano-hydrogels show obvious specific binding to the GSH high-expressing A549 cells and nonspecific binding to the GSH low-expressing A549 cells. Therefore, with this cross-linking approach, our present finding suggests that cross-linked chitosan nano-hydrogel drug carrier improves the anti-tumor effect of the A 549 cells and may serve as a potential injectable delivery carrier.

Controlled growth of titanium dioxide nanotubes for doxorubicin loading and studies of in vitro antitumor activity.

Titanium dioxide (TiO2) materials are suitable for use as drug carriers due to their natural biocompatibility and nontoxicity. The aim of the study presented in this paper was to investigate the controlled growth of TiO2 nanotubes (TiO2 NTs) of different sizes via an anodization method, in order to delineate whether the size of NTs governs their drug loading and release profile as well as their antitumor efficiency. TiO2 NTs were tailored to sizes ranging from 25 nm to 200 nm according to the anodization voltage employed. The TiO2 NTs obtained by this process were characterized using scanning electron microscopy, transmission electron microscopy, and dynamic light scattering The larger TiO2 NTs exhibited greatly improved doxorubicin (DOX)-loading capacity (up to 37.5 wt%), which contributed to their outstanding cell-killing ability, as evidenced by their lower half-maximal inhibitory concentration (IC50). Comparisons were carried out of cellular uptake and intracellular release rates of DOX for large and small TiO2 NTs loaded with DOX. The results showed that the larger TiO2 NTs represent a promising therapeutic carrier for drug loading and controlled release, which could improve cancer treatment outcomes. Therefore, TiO2 NTs of larger size are useful substances with drug-loading potency that may be used in a wide range of medical applications.