Recent advances in magnetic electrospun nanofibers for cancer theranostics application

Funding Information: This article is a result of the project PTDC/CTM-CTM/30623/2017 supported by the Lisbon Regional Operational Program (Lisboa 2020) and Alentejo Regional Operational Program (Alentejo 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund ( ERDF ). This work is funded by National Funds through FCT - Portuguese Foundation for Science and Technology, Reference UID/CTM/50025/2019 and FCT / MCTES . P.S. also acknowledges the individual contract CEECIND.03189.2020.Cancer theranostics is a recent concept that aims to combine in the same device diagnostic and therapeutic features. Magnetic nanoparticles (mNPs) are commonly used as a critical part of these systems due to their ability to respond to an external magnetic field. Consequently, mNPs can generate heat when an alternating magnetic field is applied and enhance image contrast in magnetic resonance. However, direct administration of mNPs intravenously or directly in the tumor can lead to undesired side effects because of mNP elimination by macrophages or leakage to healthy tissues. Therefore, mNPs can be retained in a polymeric nanofibrous mesh, thus preventing misplacing or loss of mNPs. Furthermore, these magnetic nanofibers can be directly implanted in the tumor site, thus ensuring high mNPs loading and higher magnetic response. In addition, polymeric nanofibers produced by electrospinning are frequently used to maintain a sustained drug release in the tumor site. Therefore, a magnetic polymeric nanofiber produced by electrospinning is an ideal nanosystem for cancer theranostics application. This review summarizes the most recent developments of magnetic nanofibers produced by electrospinning for cancer theranostics applications.proofinpres

Application of hyperthermia for cancer treatment: Synthesis and characterization of magnetic nanoparticles and their internalization on tumor cell lines

FEDER funds through the COMPETE 2020 Program under the project number POCI-01-0145-FEDER-007688. This work was also funded by the Scientific merit prize Santander-Totta - Lisbon New University - "Antibody engineering for breast cancer therapy" 2013. Catarina I. P. Chaparro also acknowledges the financial support from Liga Portuguesa Contra o Cancro (LPCC)/Pfizer 2017.Truncated sialylated O-glycans, such as cell-surface carbohydrate antigen sialyl-Tn (STn) are overexpressed by several cancer types, but not by the respective normal tissues. STn expression is associated with oncogenesis and metastatic ability of cancer cells, with reduced overall survival and lack of response to chemotherapy. Advances in nanomedicine have resulted in rapid development of biocompatible superparamagnetic iron oxide nanoparticles (SPIONs) with considerable potential in cancer treatment. Therefore, in this study SPIONs coated with oleic acid (OA) or dimercaptosuccinic acid (DMSA) were developed and characterized for internalization in two breast cancer cell lines: cell line expressing the STn antigen and the corresponding control. SPIONs with an average diameter of 8 nm showed superparamagnetic behavior and high potential to be used as magnetic hyperthermia agents. OA and DMSA coating provided high stability of SPIONs in physiological conditions while not changing their main properties. NPs internalization studies showed a higher accumulation of DMSA coated NPs in the breast cancer MDA-MB-231 WT cell line. In MDA-MB-231 cell line expressing STn both coated NPs showed a similar accumulation. Therefore, STn antigen can act as a receptor capable of detecting and covalently bind to the molecules present on NPs surface and induce their cellular uptake by endocytosis.publishersversionpublishe

Incorporation of dual-stimuli responsive microgels in nanofibrous membranes for cancer treatment by magnetic hyperthermia

Funding Information: This work is funded by FEDER funds through the COMPETE 2020 Program and National Funds through FCT?Portuguese Foundation for Science and Technology under the project POCI?01-0145-FEDER-007688 (Reference UID/CTM/50025) and PTDC/CTMCTM/30623/2017 (DREaMM).The delivery of multiple anti-cancer agents holds great promise for better treatments. The present work focuses on developing multifunctional materials for simultaneous and local combi-natory treatment: Chemotherapy and hyperthermia. We first produced hybrid microgels (MG), synthesized by surfactant-free emulsion polymerization, consisting of Poly (N-isopropyl acrylamide) (PNIPAAm), chitosan (40 wt.%), and iron oxide nanoparticles (NPs) (5 wt.%) as the inorganic compo-nent. PNIPAAm MGs with a hydrodynamic diameter of about 1 µm (in their swollen state) were successfully synthesized. With the incorporation of chitosan and NPs in PNIPAAm MG, a decrease in MG diameter and swelling capacity was observed, without affecting their thermosensitivity. We then sought to produce biocompatible and mechanically robust membranes containing these dual-responsive MG. To achieve this, MG were incorporated in poly (vinyl pyrrolidone) (PVP) fibers through colloidal electrospinning. The presence of NPs in MG decreases the membrane swelling ratio from 10 to values between 6 and 7, and increases the material stiffness, raising its Young modulus from 20 to 35 MPa. Furthermore, magnetic hyperthermia assay shows that PVP-MG-NP composites perform better than any other formulation, with a temperature variation of about 1◦C. The present work demonstrates the potential of using multifunctional colloidal membranes for magnetic hyperthermia and may in the future be used as an alternative treatment for cancer.publishersversionpublishe

Injectable composite systems based on microparticles in hydrogels for bioactive cargo controlled delivery

Funding Information: Funding: This work is funded by FEDER funds through the COMPETE 2020 Program and National Funds through FCT—Portuguese Foundation for Science and Technology under the project POCI— 01-0145-FEDER-007688 (Reference UID/CTM/50025) and PTDC/CTMCTM/30623/2017 (DREaMM). H.C. also acknowledges FCT for the PhD grant with reference SFRH/BD/144986/2019. P.S. also acknowledges the individual contract CEECIND.03189.2020. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Engineering drug delivery systems (DDS) aim to release bioactive cargo to a specific site within the human body safely and efficiently. Hydrogels have been used as delivery matrices in different studies due to their biocompatibility, biodegradability, and versatility in biomedical purposes. Microparticles have also been used as drug delivery systems for similar reasons. The combination of microparticles and hydrogels in a composite system has been the topic of many research works. These composite systems can be injected in loco as DDS. The hydrogel will serve as a barrier to protect the particles and retard the release of any bioactive cargo within the particles. Additionally, these systems allow different release profiles, where different loads can be released sequentially, thus allowing a synergistic treatment. The reported advantages from several studies of these systems can be of great use in biomedicine for the development of more effective DDS. This review will focus on in situ injectable microparticles in hydrogel composite DDS for biomedical purposes, where a compilation of different studies will be analysed and reported herein.publishersversionpublishe

Optimization of Hydrogel Composition based on Rheological Behavior

Funding Information: This work was financed by national funds from FCT-Fundação para a Ciência e a Tecnologia, I.P., in the scope of the projects LA/P/0037/2020, UIDP/50025/2020 and UIDB/50025/2020 of the Associate Laboratory Institute of Nanostructures, Nanomodelling and Nanofabrication–i3N. H.C. acknowledges FCT for the PhD grant with reference SFRH/BD/144986/2019 and P.S. acknowledges the individual contract CEECIND. 03189.2020. Publisher Copyright: © 2022 by the authors.Due to the high complexity of some treatments, there is a need to develop drug-delivery systems that can release multiple drugs/bioactive agents at different stages of treatment. In this study, a thermoresponsive injectable dual-release system was developed with gellan gum/alginate microparticles (GG:Alg) within a thermoresponsive Pluronic hydrogel composed of a mixture of Pluronic F127 and F68. The increase in F68 ratio and decrease in F127 lead to higher transition temperatures. The addition of the GG:Alg microparticles decreased the transition temperatures with a linear tendency. In Pluronic aqueous solutions (20 wt.%), the F127:F68 ratios of 16:4 and 17:3 (wt.%:wt.%) and the addition of microparticles (up to 15 wt.%) maintained the sol–gel transition temperatures within a suitable range (between 25 °C and 37 °C). Microparticles did not hinder the injectability of the system in the sol phase. Methylene blue was used as a model drug to evaluate the release mechanisms from microparticles, hydrogel, and composite system. The hydrogel delayed the release of methylene blue from the microparticles. The hydrogel loaded with methylene blue released at a faster rate than the microparticles within the hydrogel, thus demonstrating a dual-release profile.publishersversionpublishe

Polyvinylpyrrolidone Nanofibers Incorporating Mesoporous Bioactive Glass for Bone Tissue Engineering

Publisher Copyright: © 2023 by the authors.Composite biomaterials that combine osteoconductive and osteoinductive properties are a promising approach for bone tissue engineering (BTE) since they stimulate osteogenesis while mimicking extracellular matrix (ECM) morphology. In this context, the aim of the present research was to produce polyvinylpyrrolidone (PVP) nanofibers containing mesoporous bioactive glass (MBG) 80S15 nanoparticles. These composite materials were produced by the electrospinning technique. Design of experiments (DOE) was used to estimate the optimal electrospinning parameters to reduce average fiber diameter. The polymeric matrices were thermally crosslinked under different conditions, and the fibers’ morphology was studied using scanning electron microscopy (SEM). Evaluation of the mechanical properties of nanofibrous mats revealed a dependence on thermal crosslinking parameters and on the presence of MBG 80S15 particles inside the polymeric fibers. Degradation tests indicated that the presence of MBG led to a faster degradation of nanofibrous mats and to a higher swelling capacity. The assessment of in vitro bioactivity in simulated body fluid (SBF) was performed using MBG pellets and PVP/MBG (1:1) composites to assess if the bioactive properties of MBG 80S15 were kept when it was incorporated into PVP nanofibers. FTIR and XRD analysis along with SEM–EDS results indicated that a hydroxy-carbonate apatite (HCA) layer formed on the surface of MBG pellets and nanofibrous webs after soaking in SBF over different time periods. In general, the materials revealed no cytotoxic effects on the Saos-2 cell line. The overall results for the materials produced show the potential of the composites to be used in BTE.publishersversionpublishe

A Review

This work is co-financed by FEDER, European Funds, through the COMPETE 2020 POCI and PORL, National Funds through FCT—Portuguese Foundation for Science and Technology, and POR Lisboa2020, under the projects PIDDAC (POCI-01-0145-FEDER-007688, Reference UIDB/50025/2020-2023) and PTDC/CTMCTM/30623/2017 (DREaMM). P.S. also acknowledges the individual contract CEECIND.03189.2020. C.T. acknowledges i3N for the Ph.D. grant with reference UI/BD/151541/2021. Publisher Copyright: © 2022 by the authors.In recent decades, new and improved materials have been developed with a significant interest in three-dimensional (3D) scaffolds that can cope with the diverse needs of the expanding biomedical field and promote the required biological response in multiple applications. Due to their biocompatibility, ability to encapsulate and deliver drugs, and capacity to mimic the extracellular matrix (ECM), typical hydrogels have been extensively investigated in the biomedical and biotechnological fields. The major limitations of hydrogels include poor mechanical integrity and limited cell interaction, restricting their broad applicability. To overcome these limitations, an emerging approach, aimed at the generation of hybrid materials with synergistic effects, is focused on incorporating nanoparticles (NPs) within polymeric gels to achieve nanocomposites with tailored functionality and improved properties. This review focuses on the unique contributions of clay nanoparticles, regarding the recent developments of clay-based nanocomposite hydrogels, with an emphasis on biomedical applications.publishersversionpublishe

Electrospun composite cellulose acetate/iron oxide nanoparticles non-woven membranes for magnetic hyperthermia applications

In the present work composite membranes were produced by combining magnetic nanoparticles (NPs) with cellulose acetate (CA) membranes for magnetic hyperthermia applications. The non-woven CA membranes were produced by electrospinning technique, and magnetic NPs were incorporated by adsorption at fibers surface or by addition to the electrospinning solution. Therefore, different designs of composite membranes were obtained. Superparamagnetic NPs synthesized by chemical precipitation were stabilized either with oleic acid (OA) or dimercaptosuccinic acid (DMSA) to obtain stable suspensions at physiological pH. The incorporation of magnetic NP into CA matrix was confirmed by scanning and transmission electron microscopy. The results showed that adsorption of magnetic NPs at fibers' surface originates composite membranes with higher heating ability than those produced by incorporation of magnetic NPs inside the fibers. However, adsorption of magnetic NPs at fibers' surface can cause cytotoxicity depending on the NPs concentration. Tensile tests demonstrated a reinforcement effect caused by the incorporation of magnetic NPs in the non-woven membrane.publishe

A new long-term composite drug delivery system based on thermo-responsive hydrogel and nanoclay

Several problems and limitations faced in the treatment of many diseases can be overcome by using controlled drug delivery systems (DDS), where the active compound is transported to the target site, minimizing undesirable side effects. In situ-forming hydrogels that can be injected as viscous liquids and jellify under physiological conditions and biocompatible clay nanoparticles have been used in DDS development. In this work, polymer–clay composites based on Pluronics (F127 and F68) and nanoclays were developed, aiming at a biocompatible and injectable system for long-term controlled delivery of methylene blue (MB) as a model drug. MB release from the systems produced was carried out at 37◦C in a pH 7.4 medium. The Pluronic formulation selected (F127/F68 18/2 wt.%) displayed a sol/gel transition at approx. 30◦C, needing a 2.5 N force to be injected at 25◦C. The addition of 2 wt.% of Na116 clay decreased the sol/gel transition to 28◦C and significantly enhanced its viscoelastic modulus. The most suitable DDS for long-term application was the Na116-MB hybrid from which, after 15 days, only 3% of the encapsulated MB was released. The system developed in this work proved to be injectable, with a long-term drug delivery profile up to 45 days.publishersversionpublishe

Potassium Ferrite for Biomedical Applications

LA/P/0037/2020. LA/P/0006/2020. Publisher Copyright: © 2023 by the authors.Ferrites have been widely studied for their use in the biomedical area, mostly due to their magnetic properties, which gives them the potential to be used in diagnostics, drug delivery, and in treatment with magnetic hyperthermia, for example. In this work, KFeO2 particles were synthesized with a proteic sol-gel method using powdered coconut water as a precursor; this method is based on the principles of green chemistry. To improve its properties, the base powder obtained was subjected to multiple heat treatments at temperatures between 350 and 1300 °C. The samples obtained underwent structural, morphological, biocompatibility, and magnetic characterization. The results show that upon raising the heat treatment temperature, not only is the wanted phase detected, but also the secondary phases. To overcome these secondary phases, several different heat treatments were carried out. Using scanning electron microscopy, grains in the micrometric range were observed. Saturation magnetizations between 15.5 and 24.1 emu/g were observed for the samples containing KFeO2 with an applied field of 50 kOe at 300 K. From cellular compatibility (cytotoxicity) assays, for concentrations up to 5 mg/mL, only the samples treated at 350 °C were cytotoxic. However, the samples containing KFeO2, while being biocompatible, had low specific absorption rates (1.55–5.76 W/g).publishersversionpublishe