Combined Use of Photobiomodulation and Curcumin-Loaded Iron Oxide Nanoparticles Significantly Improved Wound Healing in Diabetic Rats Compared to Either Treatment Alone.

Introduction: Here, we assess the therapeutic effects of photobiomodulation (PBM) and curcumin (CUR)-loaded superparamagnetic iron oxide nanoparticles (SPIONs), alone or together, on the maturation step of a type 1 diabetes (DM1) rat wound model. Methods: Full-thickness wounds were inflicted in 36 rats with diabetes mellitus (DM) induced by the administration of streptozotocin (STZ). The rats were randomly allocated to four groups. Group one was untreated (control); group two received CUR; group 3 received PBM (890 nm, 80 Hz, 0.2 J/cm2); group 4 received a combination of PBM plus CUR. On days 0, 4, 7, and 15, we measured microbial flora, wound closure fraction, tensile strength, and stereological analysis. Results: All treatment groups showed a substantial escalation in the wound closure rate, a substantial reduction in the count of methicillin-resistant Staphylococcus aureus (MRSA), a substantial improvement in wound strength, a substantially improvement in stereological parameters compared to the control group, however, the PBM+CUR group was superior to the other treatment groups (all, P≤0.05). Conclusion: All treatment groups showed significantly improved wound healing in the DM1 rat model. However, the PBM+CUR group was superior to the other treatment groups and the control group in terms of wound strength and stereological parameters.

Synthesis and Characterization of SPIONs Encapsulating Polydopamine Nanoparticles and Their Test for Aqueous Cu2+ Ion Removal.

The removal of pollutants, such as heavy metals, aromatic compounds, dyes, pesticides and pharmaceuticals, from water is still an open challenge. Many methods have been developed and exploited for the purification of water from contaminants, including photocatalytic degradation, biological treatment, adsorption and chemical precipitation. Absorption-based techniques are still considered among the most efficient and commonly used approaches thanks to their operational simplicity. In recent years, polydopamine-coated magnetic nanoparticles have emerged for the uptake of heavy metals in water treatment, since they combine specific affinity towards pollutants and magnetic separation capacity. In this context, this work focuses on the synthesis of polydopamine (PDA)-coated Super Paramagnetic Iron Oxide Nanoparticles (PDA@SPIONs) as adsorbents for Cu2+ ions, designed to serve as functional nanostructures for the removal of Cu2+ from water by applying a magnetic field. The synthetic parameters, including the amount of SPIONs and PDA, were thoroughly investigated to define their effects on the nanostructure features and properties. Subsequently, the ability of the magnetic nanostructures to bind metal ions was assessed on Cu2+-containing solutions. A systematic investigation of the prepared functional nanostructures was carried out by means of complementary spectroscopic, morphological and magnetic techniques. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) measurements were performed in order to estimate the Cu2+ binding ability. The overall results indicate that these nanostructures hold great promise for future bioremediation applications.

The Surface Amine Group of Ultrasmall Magnetic Iron Oxide Nanoparticles Produce Analgesia in the Spinal Cord and Decrease Long-Term Potentiation.

Our previous studies have revealed the ultrasmall superparamagnetic iron oxide in the amine group USPIO-101 has an analgesic effect on inflammatory pain. Here, we further investigated its effect on the spinal cord and brain via electrophysiological and molecular methods. We used a mouse inflammatory pain model, induced by complete Freund's adjuvant (CFA), and measured pain thresholds via von Frey methods. We also investigated the effects of USPIO-101 via an extracellular electrophysiological recording at the spinal dorsal horn synapses and hippocampal Schaffer collateral-CA1 synapses, respectively. The mRNA expression of pro-inflammatory cytokines was detected by quantitative real-time polymerase chain reaction (RT-qPCR). Our results showed intrathecal USPIO-101 produces similar analgesic behavior in mice with chronic inflammatory pain via intrathecal or intraplantar administration. The potentiated low-frequency stimulation-induced spinal cord long-term potentiation (LTP) at the spinal cord superficial dorsal horn synapses could decrease via USPIO-101 in mice with chronic inflammatory pain. However, the mRNA expression of cyclooxygenase-2 was enhanced with lipopolysaccharide (LPS) stimulation in microglial cells, and we also found USPIO-101 at 30 µg/mL could decrease the magnitude of hippocampal LTP. These findings revealed that intrathecal USPIO-101 presented an analgesia effect at the spinal cord level, but had neurotoxicity risk at higher doses.

Enhancement of CD8+ T-Cell-Mediated Tumor Immunotherapy via Magnetic Hyperthermia.

Magnetic hyperthermia (MHT) uses magnetic iron oxide nanoparticles (MIONs) to irradiate heat when subjected to an alternating magnetic field (AMF), which then trigger a series of biological effects to realize rapid tumor-killing effects. With the deepening in research, MHT has also shown significant potential in achieving antitumor immunity. On the other hand, immunotherapy in cancer treatment has gained increasing attention over recent years and excellent results have generally been reported. Using MHT to activate antitumor immunity and clarifying its synergistic mechanism, i. e., immunogenic cell death (ICD) and immunosuppressive tumor microenvironment (TME) reversal, can achieve a synergistically enhanced therapeutic effect on primary tumors and metastatic lesions, and this can prevent cancer recurrence and metastasis, which thus prolong survival. In this review, we discussed the role of MHT when utilized alone and combining MHT with other treatments (such as radiotherapy, photodynamic therapy, and immune checkpoint blockers) in the process of tumor immunotherapy, including antigen release, dendritic cells (DCs) maturation, and activation of CD8+ cytotoxic T lymphocytes. Finally, the challenges and future development of current MHT and immunotherapy are discussed.

Efeitos antibiofilme e citotóxico de um novo nanosistema carreador de clorexidina e fluconazol / Antibiofilm and cytotoxic effects of a new nanocarrier of chlorhexidine and fluconazole

Os objetivos do presente estudo foram montar e caracterizar um novo nanocarreador dual de clorexidina (CLX) e fluconazol (FLZ), bem como avaliar seu efeito sobre biofilmes microcosmos e sua citotoxicidade sobre queratinócitos orais. Para montar o nanocarreador dual, CLX e FLZ foram adicionados a nanopartículas de óxido de ferro (NPsOF) previamente revestidas por quitosana (QTS), seguido de um processo de solubilização sob agitação magnética. O nanocarreador foi, então, caracterizado por microscopia eletrônica de transmissão, difração de raios X, espectroscopia no infravermelho por transformada de Fourier e análise termogravimétrica. A suscetibilidade de Candida albicans e Candida glabrata no estado planctônico ao nanocarreador dual foi determinada pelos valores de concentração inibitória mínima, utilizando o método da microdiluição em caldo. Um pool de saliva de 2 doadores saudáveis suplementado com espécies de Candida foi usado como inóculo para a formação de biofilmes microcosmos. Os biofilmes foram cultivados (72 h) sobre discos de vidro posicionados no Amsterdam Active Attachment model e tratados (24 h) com NPsOF-QTS carreando 39 µg/mL de CLX + 156 µg/mL de FLZ (NPsOF-QTS-CLX39-FLZ156), 78 µg/mL de CLX + 312 µg/mL de FLZ (NPsOF-QTS-CLX78-FLZ312) e 156 µg/mL de CLX + 624 µg/mL de FLZ (NPsOF-QTS-CLX156-FLZ624). NPsOF (218,5 µg/mL), QTS (218,5 µg/mL) e 156 µg/mL de CLX + 624 µg/mL de FLZ (CLX156-FLZ624) foram testados como controles. Posteriormente, foram realizadas as análises de quantificação das unidades formadoras de colônias (UFCs), produção de ácido lático (LA), composição da matriz extracelular (ME) e viabilidade celular por microscopia confocal de varredura a laser (MCVL). Para o ensaio de citotoxicidade, queratinócitos orais humanos (linhagem NOKsi) foram expostos a diferentes concentrações do nanocarreador dual, por 24 ou 48 h, e a viabilidade celular foi determinada pelo ensaio de redução de MTT. Os dados foram analisados por ANOVA ou teste de Kruskal-Wallis, seguidos dos testes de Fisher LSD ou Tukey (α = 0,05). Os testes de caracterização físico-química mostraram que um nanocarreador dual com dimensões em torno de 6 nm foi obtido, sem comprometer a propriedade cristalina e a estabilidade de NPsOF. Os compostos que formam o nanocarreador estabeleceram uma interação sinérgica em relação ao efeito sobre células planctônicas de Candida. Para os ensaios de biofilme, NPsOF-QTS-CLX156-FLZ624 foi o composto mais eficaz na redução de UFCs de Streptococcus mutans, Lactobacillus spp., C. albicans e C. glabrata, diferindo significativamente dos outros grupos, e esses achados foram confirmados por MCVL. NPsOF-QTS-CLX39-FLZ156, NPsOF-QTS-CLX78-FLZ312 e CLX156- FLZ624 mostraram efeitos antibiofilme similares. O nanocarreador dual também reduziu significativamente a produção de AL e a quantidade de carboidratos e ácidos nucleicos da ME. Um efeito citotóxico dose-dependente sobre queratinócitos orais foi observado para o nanocarreador dual, independentemente do período de exposição testado (24 ou 48 h). NPsOF-QTS-CLX-FLZ e CLX-FLZ reduziram significativamente a viabilidade dos queratinócitos em concentrações de CLX e FLZ iguais ou superiores a 7,8 e 31,25 µg/mL, respectivamente. Por fim, a nanoterapia testada no presente estudo é promissora e constitui um grande avanço dentro dos métodos alternativos aos antimicrobianos tradicionais para o controle da candidíase oral(AU)

The objectives of the present study were to assemble and characterize a new dual nanocarrier of chlorhexidine (CHX) and fluconazole (FLZ), and evaluate its effect on microcosm biofilms and its cytotoxicity against oral keratinocytes. To assemble the dual nanocarrier, CHX and FLZ were added to iron oxide nanoparticles (IONPs) previously coated by chitosan (CS), followed by a solubilization process under magnetic stirring. The nanocarrier was then characterized by transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The susceptibility of Candida albicans and Candida glabrata in the planktonic state to the dual nanocarrier was determined by the minimum inhibitory concentration values, using the broth microdilution method. A saliva pool from 2 healthy donors supplemented with Candida species was used as an inoculum for microcosm biofilm formation. Biofilms were grown (72 h) on glass discs positioned in the Amsterdam Active Attachment model and treated (24 h) with IONPs-CS carrying 39 µg/mL CHX + 156 µg/mL FLZ (IONPsCS-CHX39-FLZ156), 78 µg/mL CHX + 312 µg/mL FLZ (IONPs-CS-CHX78-FLZ312), and 156 µg/mL CHX + 624 µg/mL FLZ (IONPs-CS-CHX156-FLZ624). IONPs at 218.5 µg/mL, 218.5 µg/mL CS, and 156 µg/mL CHX + 624 µg/mL FLZ (CHX156-FLZ624) were tested as controls. Next, analyses of the quantification of colony-forming units (CFUs), lactic acid production (LA), composition of the extracellular matrix (EM), and viability by confocal laser scanning microscopy (CLSM) were performed. For the cytotoxicity assay, human oral keratinocytes (NOKsi lineage) were exposed to different concentrations of the dual nanocarrier, for 24 or 48 h, and cell viability was determined by the MTT reduction assay. Data were analyzed by ANOVA or Kruskal-Wallis test, followed by Fisher LSD or Tukey tests (α = 0.05). The physico-chemical characterization tests showed that a dual nanocarrier with dimensions around 6 nm was assembled, without compromising the crystalline property and stability of IONPs. The compounds that form the nanocarrier established a synergistic interaction in relation to the effect on Candida planktonic cells. Regarding biofilm assays, IONPs-CS-CHX156-FLZ624 was the most effective compound in reducing CFUs from Streptococcus mutans, Lactobacillus spp., C. albicans, and C. glabrata, differing significantly from the other groups, and these findings were confirmed by CLSM. IONPs-CS-CHX39-FLZ156, IONPs-CS-CHX78-FLZ312, and CHX156-FLZ624 showed similar antibiofilm effects. The dual nanocarrier also significantly reduced LA production and the amount of carbohydrates and nucleic acids from the EM. A dose-dependent cytotoxic effect against oral keratinocytes was observed for the dual nanocarrier, regardless of the exposure period tested (24 or 48 h). IONPs-CSCHX-FLZ and CHX-FLZ significantly reduced keratinocyte viability at CHX and FLZ concentrations equal to or greater than 7.8 and 31.25 µg/mL, respectively. In conclusion, the nanotherapy tested in the current study is promising and constitutes a major advance in alternative methods to traditional antimicrobials for oral candidiasis control(AU)

Improved Stability and Photothermal Performance of Polydopamine-Modified Fe3 O4 Nanocomposites for Highly Efficient Magnetic Resonance Imaging-Guided Photothermal Therapy.

Magnetic nanomaterials are a promising class of contrast agents for magnetic resonance imaging (MRI). However, their poor stability and low relaxivity are major challenges hindering their clinical applications. In this study, magnetic theranostic nanoagents based on polydopamine-modified Fe3 O4 (Fe3 O4 @PDA) nanocomposites are fabricated for MRI-guided photothermal therapy (PTT) cancer treatments. Their high transverse relaxivity of 337.8 mM-1 s-1 makes these Fe3 O4 @PDA nanocomposites a promising T2 -weighted MRI contrast agent for cancer diagnosis and image-guided cancer therapy. Due to the good photothermal effect of polydopamine (PDA), the tumors of 4T1 tumor-bearing mice are completely excised by PTT. Most importantly, the PDA shell also improves the stability of the Fe3 O4 @PDA nanocomposites, which contributes to their excellent, long-term performance in MRI and PTT applications. Their good stability, high T2 relaxivity, robust biocompatibility, and satisfactory treatment effect give these Fe3 O4 @PDA nanocomposites great potential for use in cancer theranostics.

Multifunctional magnetic iron oxide nanoparticles: an advanced platform for cancer theranostics.

Multifunctional magnetic nanoparticles and derivative nanocomposites have aroused great concern for multimode imaging and cancer synergistic therapies in recent years. Among the rest, functional magnetic iron oxide nanoparticles (Fe3O4 NPs) have shown great potential as an advanced platform because of their inherent magnetic resonance imaging (MRI), biocatalytic activity (nanozyme), magnetic hyperthermia treatment (MHT), photo-responsive therapy and drug delivery for chemotherapy and gene therapy. Magnetic Fe3O4 NPs can be synthesized through several methods and easily surface modified with biocompatible materials or active targeting moieties. The MRI capacity could be appropriately modulated to induce response between T1 and T2 modes by controlling the size distribution of Fe3O4 NPs. Besides, small-size nanoparticles are also desired due to the enhanced permeation and retention (EPR) effect, thus the imaging and therapeutic efficiency of Fe3O4 NP-based platforms can be further improved. Here, we firstly retrospect the typical synthesis and surface modification methods of magnetic Fe3O4 NPs. Then, the latest biomedical application including responsive MRI, multimodal imaging, nanozyme, MHT, photo-responsive therapy and drug delivery, the mechanism of corresponding treatments and cooperation therapeutics of multifunctional Fe3O4 NPs are also be explained. Finally, we also outline a brief discussion and perspective on the possibility of further clinical translations of these multifunctional nanomaterials. This review would provide a comprehensive reference for readers to understand the multifunctional Fe3O4 NPs in cancer diagnosis and treatment.

Antibody-modified magnetic nanoparticles as specific high-efficient cell-separation agents.

Separation of tumor cells is a promising approach that helps not only in early detection of cancer but also as an efficient tool that holds great importance in prohibiting cancer cell mutation, drug resistance to treatments, and in granting successful adjuvant therapies. As one of the highly efficient processes for the separation of single cells, tumor cells, and specific proteins from fresh whole blood, a magnetic iron oxide nanoparticle (IONP)-based immunomagnetic separation technique has been developed in this article. The synthesized IONPs were modified with antibodies (Abs) against human epithelial growth factor receptor 2 (HER2), which is overexpressed and/or amplified in about 15% of breast cancer patients with several types of human cancer cells. The prepared Ab-conjugated IONPs (Ab-IONPs) attach HER2-positive cancer cells exclusively and can serve as specific high-efficient single-cell separation agents. The results showed that the magnetic IONPs have been successfully attached to the Abs via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide linkers. Maximum targeting efficiency of the Ab-IONP complex, which was 94.5 ± 0.8% for BT474 and 70.6 ± 0.4% for mixture of cells (BT474 and MCF7), was achieved with a minimum amount of Abs, to provide an economically efficient single-cell detection device.

Iron oxide nanoparticles - In vivo/in vitro biomedical applications and in silico studies.

The review presents a broad overview of the biomedical applications of surface functionalized iron oxide nanoparticles (IONPs) as magnetic resonance imaging (MRI) agents for sensitive and precise diagnosis tool and synergistic combination with other imaging modalities. Then, the recent progress in therapeutic applications, such as hyperthermia is discussed and the available toxicity data of magnetic nanoparticles concerning in vitro and in vivo biomedical applications are addressed. This review also presents the available computer models using molecular dynamics (MD), Monte Carlo (MC) and density functional theory (DFT), as a basis for a complete understanding of the behaviour and morphology of functionalized IONPs, for improving NPs surface design and expanding the potential applications in nanomedicine.