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, H_D = 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.

Magnetite nanoparticles are one of the most promising ferrofluids for hyperthermia applications due to the combination of unique physicochemical and magnetic properties. In this study, we designed and produced superparamagnetic ferrofluids composed of magnetite (Fe₃O₄, MION) and cobalt-doped magnetite (Co_x-MION, x = 3, 5, and 10% mol of cobalt) nanoconjugates through an eco-friendly aqueous method using carboxymethylcellulose (CMC) as the biocompatible macromolecular ligand. The effect of the gradual increase of cobalt content in Fe₃O₄ nanocolloids was investigated in-depth using XRD, XRF, XPS, FTIR, DLS, zeta potential, EMR, and VSM analyses. Additionally, the cytotoxicity of these nanoconjugates and their ability to cause cancer cell death through heat induction were evaluated by MTT assays in vitro. The results demonstrated that the progressive substitution of Co in the magnetite host material significantly affected the magnetic anisotropy properties of the ferrofluids. Therefore, Co-doped ferrite (Co_xFe_(3−x)O₄) nanoconjugates enhanced the cell-killing activities in magnetic hyperthermia experiments under alternating magnetic field performed with human brain cancer cells (U87). On the other hand, the Co-doping process retained the pristine inverse spinel crystalline structure of MIONs, and it has not significantly altered the average nanoparticle size (ca.∼7.1 ± 1.6 nm). Thus, the incorporation of cobalt into magnetite-polymer nanostructures may constitute a smart strategy for tuning their magnetothermal capability towards cancer therapy by heat generation.

Doping calcium phosphates with ionic species can play an important role in biological responses promoting alkaline phosphatase activity, and, therefore inducing the generation of new bone. Thus, in this study, the synthesis of niobium-doped hydroxyapatite (Nb-HA) nanosize particles obtained by the precipitation process in aqueous media followed by thermal treatment is presented. The bioceramics were extensively characterized by X-ray diffraction, wavelength dispersive X-ray fluorescence spectrometry, Fourier transform infrared spectroscopy, scanning electron microscopy/energy dispersive X-ray spectroscopy analysis, transmission electron microscopy, atomic force microscopy and thermal analysis regarding their chemical composition, structure and morphology. The results showed that the precipitate dried at 110 °C was composed of amorphous calcium phosphate and HA, with polidisperse particles ranging from micro to nano dimensions. After the thermal treatment at 900 °C, the bioceramic system evolved predominantly to HA crystalline phase, with evident features of particle sintering and reduction of surface area. Moreover, the addition of 10 mol% of niobium salt precursor during the synthesis indicated the complete incorporation of the Nb(V) species in the HA crystals with detectable changes in the original lattice parameters. Furthermore, the incorporation of Nb ions caused a significant refinement on the average particle size of HA. Finally, the preliminary cytocompatibility response of the biomaterials was accessed by human osteoblast cell culture using MTT and resazurin assays, which demonstrated no cytotoxicity of the Nb-alloyed hydroxyapatite. Thus, these findings seem promising for developing innovative Nb-doped calcium phosphates as artificial biomaterials for potential use in bone replacements and repair.

Glioblastoma remains the most lethal form of brain cancer, where hybrid nanomaterials biofunctionalized with polysaccharide peptides offer disruptive strategies relying on passive/active targeting and multimodal therapy for killing cancer cells. Thus, in this research, we report for the first time the rational design and synthesis of novel hybrid colloidal nanostructures composed of gold nanoparticles stabilized by trisodium citrate (AuNP@TSC) as the oxidase-like nanozyme, coupled with cobalt-doped superparamagnetic iron oxide nanoparticles stabilized by carboxymethylcellulose ligands (Co-MION@CMC) as the peroxidase-like nanozyme. They formed inorganic–inorganic dual-nanozyme systems functionalized by a carboxymethylcellulose biopolymer organic shell, which can trigger a biocatalytic cascade reaction in the cancer tumor microenvironment for the combination of magnetothermal–chemodynamic therapy. These nanoassemblies were produced through a green aqueous process under mild conditions and chemically biofunctionalized with integrin-targeting peptide (iRDG), creating bioengineered nanocarriers. The results demonstrated that the oxidase-like nanozyme (AuNP) was produced with a crystalline face-centered cubic nanostructure, spherical morphology (diameter = 16 ± 3 nm), zeta potential (ZP) of −50 ± 5 mV, and hydrodynamic diameter (D_H) of 15 ± 1 nm. The peroxide-like nanostructure (POD, Co-MION@CMC) contained an inorganic crystalline core of magnetite and had a uniform spherical shape (2R = 7 ± 1 nm) which, summed to the contribution of the CMC shell, rendered a hydrodynamic diameter of 45 ± 4 nm and a negative surface charge (ZP = −41 ± 5 mV). Upon coupling both nanozymes, water-dispersible colloidal supramolecular vesicle-like organic–inorganic nanostructures were produced (AuNP//Co-MION@CMC, ZP = −45 ± 4 mV and D_H = 28 ± 3 nm). They confirmed dual-nanozyme cascade biocatalytic activity targeted by polymer–peptide conjugates (AuNP//Co-MION@CMC_iRGD, ZP = −29 ± 3 mV and D_H = 60 ± 4 nm) to kill brain cancer cells (i.e., bioenergy “starvation” by glucose deprivation and oxidative stress through reactive oxygen species generation), which was boosted by the magneto-hyperthermotherapy effect when submitted to the alternating magnetic field (i.e., induced local thermal stress by “nanoheaters”). This groundwork offers a wide avenue of opportunities to develop innovative theranostic nanoplatforms with multiple integrated functionalities for fighting cancer and reducing the harsh side effects of conventional chemotherapy.