Glioblastoma is the most aggressive primary brain cancer, which has no cure yet. Emerging nanotheranostic alternatives such as magnetic iron oxide nanoparticles (MIONs) have great potential as multimodal cancer therapy mediators. They can act as nanocarriers of anticancer drugs and generate localized heat when exposed to an alternating magnetic field (AMF), resulting in combined effects of chemotherapy and magnetic hyperthermia therapy. Thus, we designed and synthesized novel MIONs directly through a co-precipitation method by a single step one-pot aqueous green process using carboxymethylcellulose (CMC) as a multifunctional, biocompatible and water-soluble biopolymer ligand (iron oxide nanoparticle–CMC, MION@CMC). They were bioconjugated via amide bonds with doxorubicin (DOX, an anticancer drug) forming nanohybrids (MION@CMC–DOX). The CMC, MION@CMC and MION@CMC–DOX nanoconjugates were comprehensively characterized by 1HNMR, FTIR, TEM/SAED/EDX, UV-visible, XRD, zeta potential (ZP) and DLS analyses. Moreover, cytotoxicity and cell killing activities of these nanoconjugates were assessed by in vitro biological assays. The nanoconjugates were incubated with glioma cells (U87), a magnetic hyperthermia (MHT) assay was performed for evaluating the activity against brain cancer cells and confocal laser scanning laser microscopy was used for bioimaging their cellular uptake pathways. The results showed that fairly monodisperse and water-soluble ultra-small iron oxide nanoparticles (Fe3O4) were synthesized (core size = 7 ± 2 nm) and stabilized by CMC producing negatively charged nanocolloids (−38 ± 3 mV, MION@CMC; hydrodynamic radius, HD = 38 ± 2 nm). The results confirmed the conjugation of MION@CMC with DOX by amide bonds, leading to the development of magnetopolymersome nanostructures (MION@CMC–DOX). The cell viability bioassays evidenced low toxicity of MION@CMC compared to the severe cytotoxicity of MION@CMC–DOX nanosystems mainly caused by the release of DOX. Under an alternating magnetic field, MION@CMC and MION@CMC–DOX systems demonstrated activity for killing U87 cancer cells due to the heat generated by hyperthermia. In addition, the MION@CMC–DOX bioconjugates showed significantly higher cell killing response when exposed to an AMF due to the combined chemotherapy effect of DOX release inside the cancer cells triggering apoptotic pathways.
The burden of chronic wounds is growing due to the increasing incidence of trauma, aging, and diabetes, resulting in therapeutic problems and increased medical costs. Thus, this study reports the synthesis and comprehensive characterization of water-responsive hybrid hydrogels based on carboxymethyl cellulose (CMC) and poly(vinyl alcohol) (PVA) using citric acid (CA) as the chemical crosslinking agent, with tunable physicochemical properties suitable to be applied as a wound dressing for soft tissue engineering applications. They were produced through an eco-friendly process under mild conditions. The hydrogels were designed and produced with flexible swelling degree properties through the selection of CMC molecular mass (Mw = 250 and 700 kDa) and degree of functionalization (DS = 0.81), degree of hydrolysis of PVA (DH > 99%, Mw = 84–150 kDa) associated with synthesis parameters, CMC/PVA ratio and extension of chemical crosslinking (CA/CMC:PVA ratio), for building engineered hybrid networks. The results demonstrated that highly absorbent hydrogels were produced with swelling degrees ranging from 100% to 5000%, and gel fraction from 40% to 80%, which significantly depended on the concentration of CA crosslinker and the presence of PVA as the CMC-based network modifier. The characterizations indicated that the crosslinking mechanism was mostly associated with the chemical reaction of CA carboxylic groups with hydroxyl groups of CMC and PVA polymers forming ester bonds, rendering a hybrid polymeric network. These hybrid hydrogels also presented hydrophilicity, permeability, and structural features dependent on the degree of crosslinking and composition. The hydrogels were cytocompatible with in vitro cell viability responses of over 90% towards model cell lines. Hence, it is envisioned that this research provides a simple strategy for producing biocompatible hydrogels with tailored properties as wound dressings for assisting chronic wound healing and skin tissue engineering applications.