Dual temperature- and magnetic-responsive PNIPAAm-based nanogels for tunable and drug release.

Magnetothermally Responsive Mesoporous Silica Nanocarriers: Materials Design, Thermoresponsive Gates and Controlled Drug Release

Magnetothermally responsive nanocarriers represent a promising platform for spatio-temporally controlled drug delivery by combining alternating magnetic field (AMF)-induced heating with thermally triggered cargo release. Among the available architectures, magnetite-core/mesoporous-silica-shell (Fe3O4@mSiO2) nanoparticles functionalized with thermoresponsive polymer gatekeepers are particularly attractive. These systems integrate a magnetic heat source, a mesoporous drug reservoir, and temperature-dependent control of pore accessibility. This review examines the fundamental principles of magnetic hyperthermia, including heat-generation mechanisms, specific absorption rate (SAR), intrinsic loss power (ILP), AMF parameters and safety, and the interplay between Néel and Brownian relaxation. It also critically discusses core–shell synthesis and architecture, drug-loading strategies, PNIPAM-, PNVCL-, and other LCST-type gatekeepers, and the physicochemical characterization required to validate the complete nanocarrier. Evidence for combined magnetic hyperthermia and chemotherapy is assessed together with hemocompatibility, immunogenicity, oxidative stress, biodistribution, degradation, long-term retention, and clearance. Although promising magnetothermal release and therapeutic effects have been reported, evidence remains dominated by in vitro studies, with limited in vivo validation. Current clinical experience concerns locally administered iron-oxide hyperthermia rather than complete thermoresponsive Fe3O4@mSiO2 drug-delivery systems. Translation will require standardized magnetothermal and release testing, reproducible scale-up, validated sterilization and endotoxin control, component-resolved pharmacokinetics, and integrated development of the nanocarrier and AMF applicator.

Engineering Chitosan-Functionalized Magnetopolymeric Nanoparticles as a Theranostic Platform for MRI-Guided Magnetic Hyperthermia

Magnetopolymeric nanocomposites represent promising platforms for advanced nanomedicine due to their ability to combine magnetic responsiveness with polymer-mediated biological functionality. In this study, a hybrid nanocomposite system based on maghemite (Mh), poly(ethyl cyanoacrylate) (PECA), and chitosan (Cs) was developed and systematically characterized for biomedical applications. Mh nanoparticles (NPs) were incorporated as magnetic cores, while PECA acted as a biodegradable polymeric matrix, and chitosan provided surface functionalization and enhanced biocompatibility. The nanocomposites were prepared following anionic polymerization and coacervation methods and characterized in terms of structure particle size, electrokinetics and magnetic responsiveness. The results demonstrated the formation of a nanoscale (core/shell)/shell system with superparamagnetic properties. Importantly, the nanocomposites were evaluated as magnetic resonance imaging (MRI) contrast agents, exhibiting significant transverse relaxivity. In vitro cytotoxicity assays demonstrated the absence of significant toxic effects, while ex vivo hemocompatibility studies confirmed their compatibility with blood components. Furthermore, their potential as hyperthermia agents was demonstrated in vitro under the influence of an alternating magnetic field (AMF). Overall, the (core@shell)@shell nanocomposites combined superparamagnetic functionalities with favorable biological properties, supporting their potential use as multifunctional platforms for theranostic applications, including MRI contrast enhancement and magnetically induced hyperthermia.

pH-responsive microneedle patches based on poly(dextran-co-methacrylic acid) hydrogels for controlled drug release.

This study reports the synthesis, characterization, and biological evaluation of pH-responsive dextran-based hydrogel microneedles (MNs) for controlled drug delivery. Dextran (Dex) was chemically modified with glycidyl methacrylate (GMA) to obtain dextran methacrylate (DexMA), which was copolymerized with methacrylic acid (MAA) via free-radical polymerization to produce poly(DexMA-co-MAA) hydrogels with different compositions. The successful modification of Dex and copolymer formation were confirmed by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (1H NMR), thermogravimetric analyses (TGA), and scanning electron microscopy (SEM). The hydrogels exhibited pH-responsive swelling behavior, influenced by the DexMA:MAA ratio. Hydrogel-based MNs patches were fabricated using micromolding, producing well-defined pyramidal structures (450 μm × 200 μm). Doxorubicin (DOX) was incorporated as a model anticancer drug, and its release profile was evaluated at pH 5.5, 6.8, and 7.4. Release kinetics were analyzed using multiple mathematical models, with Korsmeyer-Peppas model providing the best fit, suggesting anomalous transport governed by diffusion and polymer relaxation mechanisms. Cytocompatibility of MNs formulations was assessed through indirect contact MTT assays using human fibroblast 1132SK cells. Cell viability remained above the threshold established by ISO 10993-5 standard, indicating low cytotoxicity and biocompatibility. Overall, these results demonstrate that poly(DexMA-co-MAA) hydrogel MNs represent a promising platform for controlled drug delivery.

Dual-Layered, pH-Responsive PLGA-Based Nanocarriers for Enhanced Niclosamide Delivery and Anticancer Activity.

The clinical translation of niclosamide as an anticancer drug remains as a significant challenge mainly due to its poor aqueous solubility. To address this, a dual layered nanocarrier system, PLGA@Na-CMC-CaCO3 was developed in which the presence of PLGA enhanced the encapsulation of niclosamide, Na-CMC improved the bioavailability, and CaCO3 nanoparticles helped in pH-responsive drug release. The fabricated nanocarrier exhibited a uniform size with low polydispersity index when analyzed using DLS. The stepwise incorporation of all the elements along with the drug was confirmed using FTIR and XRD, and the thermal stability of the nanocarrier was assessed using TGA. The PLGA@Na-CMC-CaCO3 nanocarrier system demonstrated a high niclosamide encapsulation efficiency of ∼95.67%. Further a pH-dependent drug release profile was observed, with increased drug release under acidic pH mimicking the tumor microenvironment. The release kinetics followed the first-order and Higuchi models, confirming diffusion-dependent drug release. In vitro biological studies on MDA-MB-231 cells using the alamar blue assay demonstrated negligible cytotoxicity of PLGA@Na-CMC-CaCO3 nanocarriers alone, indicating their biocompatibility. In contrast, niclosamide-loaded PLGA@Na-CMC-CaCO3 nanocarriers showed enhanced dose-dependent cytotoxicity compared to niclosamide alone. The presence of apoptosis in niclosamide-loaded PLGA@Na-CMC-CaCO3 nanocarriers was confirmed by the JC-1 assay, which clearly demonstrated a dose-dependent decrease in mitochondrial membrane potential in the drug encapsulated nanocarrier system. Overall, this PLGA@Na-CMC-CaCO3 nanocarrier system has the potential to effectively address the key limitations of niclosamide delivery for improved cancer therapy.

Multifunctional Magnetothermo-Responsive Smart Hydrogel for On-Demand Controlled Drug Release in Cancer Therapy.

Targeted and on-demand drug delivery technologies have attracted considerable interest for personalized cancer therapies. In this study, we developed a UV-crosslinkable and thermo-responsive gelatin methacrylate (GelMa)-poly(N-isopropylacrylamide) (PNIPAM) (G/P) hybrid hydrogel, integrated with folic acid-functionalized superparamagnetic iron oxide nanoparticles (SPIONs). Differential scanning calorimetry (DSC) and alternating magnetic field (AMF) evaluations confirmed that introducing GelMa modulated the lower critical solution temperature (LCST) to approximately 32 °C while enabling efficient magnetothermal response. Cyclic compression tests demonstrated superior mechanical properties. The 2.5G/P hydrogel achieved a compressive strength of 0.06 MPa at 78% strain, outperforming pure GelMa (0.023 MPa) and PNIPAM (0.012 MPa), with the highest modulus of elasticity at both 25 and 37 °C. In vitro biocompatibility assays using L929 fibroblasts indicated excellent cytocompatibility with >70% viability over 7 days. Furthermore, the hydrogel demonstrated excellent blood compatibility with a hemolysis ratio below 2%, complying with ISO 10993-4 standards. Synergistic reduction in cell viability was observed in human lung adenocarcinoma (NCI-H1975) and fibroblast-like osteosarcoma (MG-63) cell lines when combining drug loading and simulated AMF thermal stimulation. Triggered by hyperthermia at 41 °C, the hydrogel demonstrated a highly controlled, pulsatile 'ON/OFF' drug release profile of 5-fluorouracil (5-FU) driven by network shrinkage, achieving a maximum cumulative release of 72.6% over 28 days with a well-defined biphasic kinetic pattern. These results show that this dual-stimuli responsive hydrogel is a mechanically robust, highly efficient platform for controlled cancer therapy.

Size-Dependent Thermoresponsive Magnetic Core/Shell Nanoparticles for Controlled Doxorubicin Release and Hyperthermia-Assisted Cancer Therapy