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Although doxorubicin (Dox) has been widely used in the treatment of different types of cancer, its insufficient cellular uptake and intracellular release is still a limitation. Herein, we report an easy process for the preparation of redox-sensitive nanogels that were shown to be highly efficient in the intracellular delivery of Dox. The nanogels (AG/Cys) were obtained through in situ cross-linking of alginate (AG) using cystamine (Cys) as a cross-linker via a miniemulsion method. Dox was loaded into the AG/Cys nanogels by simply mixing it in aqueous solution with the nanogels, that is, by the establishment of electrostatic interactions between the anionic AG and the cationic Dox. The results demonstrated that the AG/Cys nanogels are cytocompatible, have a high drug encapsulation efficiency (95.2 ± 4.7%), show an in vitro accelerated release of Dox in conditions that mimic the intracellular reductive conditions, and can quickly be taken up by CAL-72 cells (an osteosarcoma cell line), resulting in higher Dox intracellular accumulation and a remarkable cell death extension when compared with free Dox. The developed nanogels can be used as a tool to overcome the problem of Dox resistance in anticancer treatments and possibly be used for the delivery of other cationic drugs in applications beyond cancer.

We present a facile approach to immobilizing zerovalent iron nanoparticles (ZVI NPs) into electrospun polymer nanofibrous mats. Electrospun poly(acrylic acid) (PAA)/poly(vinyl alcohol) (PVA) nanofibrous mats were treated at an elevated temperature to render them water stable. The water-insoluble nanofibrous mats were then used as nanoreactors to complex ferric iron for subsequent formation and immobilization of ZVI NPs. Scanning electron microscopy (SEM) studies show that the smooth, uniform morphology of the electrospun nanofibrous mats does not significantly change after immobilization with ZVI NPs. Energy-dispersive spectroscopy (EDS), Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), selected area electron diffraction (SAED), and thermogravimetric analysis (TGA) were used to characterize the polymer nanofibers before and after the immobilization of ZVI NPs. We show that the formed ZVI NPs are uniformly distributed into the electrospun nanofibers with a mean particle size of 1.6 nm. The produced ZVI NP-containing polymer nanofibrous mats exhibit a superior capability to decolorize acid fuchsine solution, a model dye in wastewater of printing and dyeing industry. Findings from this study suggest a significant potential of using the electrospun nanofibers as nanoreactors to synthesize reactive iron NPs for a broad range of environmental remediation applications providing a foundation for further rational design of various composite nanofibrous materials for various applications.

We report the complexation of a potential anticancer agent 2-methoxyestradiol (2-ME) with generation 5 (G5) poly(amidoamine) dendrimers having different surface functional groups for therapeutic applications. The complexation experiment shows that approximately 6–8 drug molecules can be complexed with one dendrimer molecule regardless the type of the dendrimer terminal groups. The bioactivity of 2-ME complexed with dendrimers was found to be significantly dependent on the surface charge of G5 dendrimers. In vitro cell biological assays show that amine, hydroxyl, and acetamide-terminated G5 dendrimers with positive, slightly positive, and close to neutral surface charges, respectively are able to deliver 2-ME to inhibit cancer cell growth. In contrast, 2-ME complexed with carboxyl-terminated G5 dendrimers with negative surface charges does not show its inherent bioactivity. Further molecular dynamics simulation studies show that the compact structure of carboxylated G5 dendrimers complexed with 2-ME does not allow the release of the drug molecules even at a pH of 5.0, which is the typical pH value in lysosome. Our findings indicate that the surface modification of dendrimers with different charges is crucial for the development of formulations of various anticancer drugs for therapeutic applications.

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