Facile Synthesis of Folic Acid-Modified Iron Oxide Nanoparticles for Targeted MR Imaging in Pulmonary Tumor Xenografts

Purpose

The purpose of this study was to develop folic acid (FA)-modified iron oxide (Fe₃O₄) nanoparticles (NPs) for targeted magnetic resonance imaging (MRI) of H460 lung carcinoma cells.

Procedures

Water-dispersible Fe₃O₄ NPs synthesized via a mild reduction method were conjugated with FA to generate FA-targeted Fe₃O₄ NPs. The specificity of FA-targeted Fe₃O₄ NPs to bind FA receptor was investigated in vitro by cellular uptake and cell MRI and in vivo by MRI of H460 tumors.

Results

The formed NPs displayed good biocompatibility and ultrahigh r ₂ relaxivity (440.01/mM/s). The targeting effect of the NPs to H460 cells was confirmed by in vitro cellular uptake and cell MRI. H460 tumors showed a significant reduction in T₂ signal intensity at 0.85 h, which then recovered and returned to control at 2.35 h.

Conclusions

The results indicate that the prepared FA-targeted Fe₃O₄ NPs have potential to be used as T₂ negative contrast agents in targeted MRI.

     

Novel one pot synthesis and spectroscopic characterization of a folate-Mn3O4 nanohybrid for potential photodynamic therapeutic application

Treatment of cancer using nanoparticles made of inorganic and metallic compounds has been increasingly used, owing to their novel intrinsic physical properties and their potential to interact with specific cellular sites, thereby significantly reducing severe secondary effects. In this study, we report a facile strategy for synthesis of folate capped Mn₃O₄ nanoparticles (FA-Mn₃O₄ NPs) with high colloidal stability in aqueous media using a hydrothermal method for potential application in photodynamic therapy (PDT) of cancer. The capping of FA to Mn₃O₄ NPs was confirmed using various spectroscopic techniques. In adenocarcinomic human alveolar basal epithelial cells (A549), the nanohybrid synthesised with a combination of FA and Mn₃O₄ shows remarkable PDT activity via intracellular ROS generation (singlet oxygen). As established by a DNA fragmentation assay and fluorescence studies, the nanohybrid can cause significant nuclear DNA damage by light induced enhanced ROS generation. In the assessment of Bax, Bcl2 provides strong evidence of apoptotic cellular death. Cumulatively, the outcomes of this study suggest that these newly synthesized FA-Mn₃O₄ NPs can specifically destroy cells with overexpressed folate receptors, thereby providing a solution in the journey of cancer eradication.

Folate capped Mn₃O₄ nanoparticles can be used in PDT for specifically destroying folate receptor-overexpressing cancer cells through photo induced free radical damage.     

Gadolinium-labelled iron/iron oxide core/shell nanoparticles as T1–T2 contrast agent for magnetic resonance imaging

Magnetic resonance imaging (MRI) is indispensable and powerful in modern clinical diagnosis and has some advantages such as non-invasiveness and high penetration depth. Furthermore, dual T₁–T₂ MR imaging has attracted crucial interest as it can decrease the risk of pseudo-positive signals in diagnosing lesions. And it''s worth nothing that the dual-mode MR imaging displays a vital platform to provide relatively comprehensive diagnosis information and receive accurate results. Herein, we report a dual T₁–T₂ MR imaging contrast agent (CA) grounded on the iron/iron oxide core/shell nanomaterials conjugated with gadolinium chelate. The Gd-labeled Fe@Fe₃O₄ NPs reveal the feasibility to utilize them to serve as a dual T₁–T₂ MR imaging CA, and the relaxivity results in a 0.5 T MR system showed a longitudinal relaxivity value (r₁) and transverse relaxivity value (r₂) of 7.2 mM⁻¹ s⁻¹ and 109.4 mM⁻¹ s⁻¹, respectively. The MTT results demonstrate the Gd-labeled Fe@Fe₃O₄ NPs have no obvious cytotoxicity and a good compatibility. The in vitro and in vivo MRI generated a brighter effect and darkening in T₁-weighted MR imaging and T₂-weighted images, respectively. The results clearly indicate that Gd-labeled Fe@Fe₃O₄ NPs have potential as a magnetic resonance imaging contrast reagent.

Magnetic resonance imaging (MRI) is indispensable and powerful in modern clinical diagnosis and has some advantages such as non-invasiveness and high penetration depth.     

Dual-response CuS@MnO2 nanoparticles with activatable CT/MR-enhanced in vivo imaging guided photothermal therapy

Although photothermal therapy (PTT) has been extensively applied in the treatment of cancer using various types of nanomaterials, low penetration of excitation light, low nanoparticle concentration enrichment and abominable nanoparticle permeation still remain huge obstacles in cancer therapy. Herein, we synthesized stable cupric sulfide nanoparticles (CuS NPs) with small size, which after functionalization with a MnO₂ coating, were employed for diagnosing and treating tumors. After reacting with an RGD peptide, the nanoparticles were able to target and focus on tumor sites. Once the nanoparticles were enriched in tumors by RGD targeting, the MnO₂ coating decomposed to Mn²⁺ ions in the tumor microenvironment. Meanwhile, the decomposition of MnO₂ allowed the dispersion of aggregated CuS NPs to enter deep tumors, and a 1064 nm laser with powerful penetration was utilized to activate CuS NPs in deep tumors for PTT. More importantly, the generated Mn²⁺ ions were used for stimuli-enhanced T₁-weighted magnetic resonance imaging (T₁-MRI) and agminated CuS NPs in tumors were accepted for computed tomography (CT) imaging. It was found that these nanocomposites can accurately indicate tumor sites after being intravenously injected, and in vitro and in vivo experiments illustrated the tremendous potential of these nanoplatforms for use in imaging-guided PTT against HepG2 tumors.

A stable multifunctional nanoplatform with superior biocompatibility and excellent targeting function was synthesized for MR/CT image guided PTT treatment, for potential application in clinical cancer treatment.     

Hyaluronic acid-mediated multifunctional iron oxide-based MRI nanoprobes for dynamic monitoring of pancreatic cancer

Regarded as the most promising technology for an early and precise detection of pancreatic cancer, a sensitive nanoprobe has been developed to enhance the accumulation of contrast agent at the tumor site. Hyaluronic acid (HA)-mediated multifunctional Fe₃O₄ nanoparticles (NPs) were used to target pancreatic cancer cells because on their cytomembrane they overexpress CD44, a receptor protein that has a high affinity to HA. The formation of HA-mediated multifunctional Fe₃O₄ nanoparticles began with the synthesis of polyethyleneimine (PEI·NH₂) stabled Fe₃O₄ NPs by slight reduction. Subsequently, the formed Fe₃O₄@PEI·NH₂ NPs were modified with fluorescein isothiocyanate (FITC), polyethylene glycol (mPEG-COOH) and HA in succession to form the multifunctional Fe₃O₄ NPs denoted as HA-Fe₃O₄ NPs. HA served as a targeting molecule to identify the surface antibody of CD44. As nanoparticles with a diameter of ca. 11.9 nm, the HA-Fe₃O₄ NPs exhibited very high r₂ relaxivity of 321.4 mM⁻¹ s⁻¹ and this has proved that HA-Fe₃O₄ NPs could be efficient T₂-weighted magnetic resonance imaging (MRI) contrast agents. In a CCK8 cell proliferation assay of HA-Fe₃O₄ NPs, there was no toxic response for Fe concentrations up to 100 μg mL⁻¹. Flow cytometry, confocal microscopy observation, and cell MRI results show that the HA-targeted groups had significantly higher cellular uptake than the nontargeted groups. This demonstrates that the HA-Fe₃O₄ NPs are uptaken by pancreatic cells via an HA-mediated targeting pathway. The HA-mediated active targeting strategy could be applied to other biomedical projects.

HA-Fe₃O₄ NPs hold enormous promise for highly efficient pancreatic tumor diagnosis as well as being CD44-mediated MR imaging contrast agents.     

Synthesis of gallotannin capped iron oxide nanoparticles and their broad spectrum biological applications

Green synthesized nanoparticles (NPs) have attracted enormous attention for their clinical and non-clinical applications. A natural polyphenol, gallo-tannin (GT) was used to reduce and cap the Fe₂O₃-NPs. GT-Fe₂O₃-NPs were synthesized following co-precipitation of FeCl₃ and FeSO₄·7H₂O with GT. Fe₂O₃-NPs absorbed light at 380 nm. Physicochemically, Fe₂O₃-NPs were spherical with slight aggregation and average diameter of 12.85 nm. X-ray diffraction confirmed crystallinity and EDX revealed the elemental percentage of iron and oxygen as 21.7% and 42.11%, respectively. FT-IR data confirmed the adsorption of gallo-tannin functional groups. Multiple drug-resistant (MDR) Escherichia coli (ESβL), Pseudomonas aeruginosa (ESβL), and Staphylococcus aureus were found susceptible to 500–1000 μg GT-Fe₂O₃-NPs per ml. In synergy, Fe₂O₃-NPs enhanced the efficiency of some antibiotics. GT-Fe₂O₃ NPs showed significant (P ≤ 0.05) inhibition of growth and biofilm against MDR E. coli, P. aeruginosa, and S. aureus causing morphological and biofilm destruction. Violacein production (quorum sensing mediated) by C. violaceum was inhibited by GT-Fe₂O₃-NPs in a concentration-dependent manner with a maximum decrease of 3.1-fold. A decrease of 11-fold and 2.32-fold in fungal mycelial growth and human breast cancer (MCF-7) cell viability, respectively was evident. This study suggests a plausible role of gallo-tannin capped Fe₂O₃-NPs as an alternative antibacterial, antiquorum sensing, antibiofilm, antifungal, and anti-proliferative agent.

Broad-spectrum biological effects of gallo-tannin capped Fe₂O₃ nanoparticles against planktonic bacteria, biofilm, fungi, and cancer cell line.     

Fe3O4@SiO2@Au nanoparticles for MRI-guided chemo/NIR photothermal therapy of cancer cells

Novel functionalized (biofunctionalization followed by cisplatin immobilization) Fe₃O₄@SiO₂@Au nanoparticles (NPs) were designed. The encapsulation of Fe₃O₄ cores inside continuous SiO₂ shells preserves their initial structure and strong magnetic properties, while the shell surface can be decorated by small Au NPs, and then cisplatin (cPt) can be successfully immobilized on their surface. The fabricated NPs exhibit very strong T₂ contrasting properties for magnetic resonance imaging (MRI). The functionalized Fe₃O₄@SiO₂@Au NPs are tested for a potential application in photothermal cancer therapy, which is simulated by irradiation of two colon cancer cell lines (SW480 and SW620) with a laser (λ = 808 nm, W = 100 mW cm⁻²). It is found that the functionalized NPs possess low toxicity towards cancer cells (∼10–15%), which however could be drastically increased by laser irradiation, leading to a mortality of the cells of ∼43–50%. This increase of the cytotoxic properties of the Fe₃O₄@SiO₂@Au NPs, due to the synergic effect between the presence of cPt plus Au NPs and laser irradiation, makes these NPs perspective agents for potential (MRI)-guided stimulated chemo-photothermal treatment of cancer.

Novel functionalized nanoparticles, with toxicity controlled by laser irradiation, are perspective agents for potential (MRI)-guided stimulated chemo-photothermal treatment of cancer.     

LyP-1 Conjugated Nanoparticles for Magnetic Resonance Imaging of Triple Negative Breast Cancer

Purpose

Triple-negative breast cancer (TNBC) does not express estrogen receptor, progesterone receptor, or Her2/neu. Both diagnosis and treatment of TNBC remain a clinical challenge. LyP-1 is a cyclic 9 amino acid peptide that can bind to breast cancer cells. The goal of this study was to design and characterize LyP-1 conjugated to fluorescent iron oxide nanoparticles (LyP-1-Fe₃O₄-Cy5.5) as a contrast agent for improved and specific magnetic resonance imaging (MRI) in a preclinical model of TNBC.

Procedures

The binding of LyP-1-Fe₃O₄-Cy5.5 to MDA-MB-231 TNBC cells was evaluated and compared to scrambled peptide bio-conjugated to iron oxide nanoparticles (Ctlpep-Fe₃O₄-Cy5.5) as a negative control. Following the in vitro study, the MDA-MB-231 cells were injected into mammary glands of nude mice. Mice were divided into two groups: control group received Ctlpep- Fe₃O₄-Cy5.5 and LyP-1 group received LyP-1-Fe₃O₄-Cy5.5 (tail vein injection at 2 mg/kg of Fe₃O₄). Mice were imaged with an in vivo fluorescence imager and a 9.4 T MRI system at various time points after contrast agent injection. The T2 relaxation time was measured to observe accumulation of the contrast agent in breast tumor and muscle for both targeted and non-targeted contrast agents.

Results

Immunofluorescence revealed dense binding of the LyP-1-Fe₃O₄-Cy5.5 contrast agent to MDA-MB-231 cells; while little appreciable binding was observed to the scrambled negative control (Ctlpep-Fe₃O₄-Cy5.5). Optical imaging performed in tumor-bearing mice showed increased fluorescent signal in mammary gland of animals injected by LyP-1-Fe₃O₄-Cy5.5 but not Ctlpep- Fe₃O₄-Cy5.5. The results were confirmed ex vivo by the 2.6-fold increase of fluorescent signal from LyP-1-Fe₃O₄-Cy5.5 in extracted tumors when compared to the negative control. In MR imaging studies, there was a statistically significant (P < 0.01) difference in normalized T2 between healthy breast and tumor tissue at 1, 2, and 24 h post injection of the LyP-1-Fe₃O₄-Cy5.5. In animals injected with LyP-1-Fe₃O₄, distinct ring-like structures were observed with clear contrast between the tumor core and rim.

Conclusion

The results demonstrate that LyP-1-Fe₃O₄ significantly improves MRI contrast of TNBC, hence has the potential to be exploited for the specific delivery of cancer therapeutics.

     

Chemiluminescent organic nanophotosensitizer for a penetration depth independent photodynamic therapy

Photodynamic therapy initiated by external photoexcitation is a clinically-approved therapeutic paradigm, but its practical application has been severely hindered by the shallow penetration of light. Here, we describe a penetration-independent PDT modality using a chemiluminescent organic nanophotosensitizer, which is activated by hydrogen peroxide instead of external photoexcitation.

A chemiluminescent organic nanophotosensitizer activated by hydrogen peroxide was fabricated for a potential penetration depth-independent photodynamic therapy.

Photodynamic therapy (PDT) performed with the cooperation of a photosensitizer, molecular oxygen and light has become a minimally non-invasive therapeutic paradigm in clinics for the treatment of various diseases such as psoriasis, vitiligo and cancer.^1–4 In general, exposing photosensitizers to suitable light, generates very toxic reactive oxygen species (mainly, single oxygen, ¹O₂) that kill tumour cells. Near-infrared light is preferred as external light to activate PDT owing to its considerably deeper penetration into tissue as compared to ultraviolet or visible light.^5,6 However, advances in PDT have been severely confined to superficial lesions for decades as all these external light-based phototherapies, including PDT, suffer from rapid attenuation of external light in tissue.⁷ Recently, Cerenkov radiation has been used as external light to break the depth dependency of PDT.^7–9 Although conceptually impressive, the expensive radiation source and inevitable DNA damage induced by ionizing radiation remain major limitations for practical applications. Therefore, it is highly desirable to develop novel better PDT with the penetration depth-independent feature.Unlike external light sources, internal light sources, such as fibre-optic light sources, could address the penetration issue and have thus been proposed as an alternative solution to activate PS, but it brings invasive problems.¹⁰ In this case, another intriguing internal light arising from chemiluminescence has been proposed for penetration depth independent PDT. In this paradigm, chemiluminescence, which occurs when a specific chemical (such as luminol) is mixed with an appropriate oxidizing agent (such as hydrogen peroxide, H₂O₂), could activate the adjacent photosensitizer to proceed to PDT. Moreover, elevated H₂O₂ levels have been found in several types of cancer cells compared to that in normal cells, potentially affording H₂O₂-activatable PDT with good selectivity. However, only few chemiluminescent PDT systems have been reported.^11–14 Moreover, these chemiluminescent PDT systems usually require coupling with additional PS to activate PDT by energy transfer, complicating the system with reduced reproducibility. In addition, to match the absorption of near-infrared absorptive PS (such as chlorin e6) for efficient energy transfer, quantum dots were usually employed to red-shift bioluminescence,^10,15 which not only complicates the system but also raises the potential of metal-induced toxicity issues.Herein, we fabricated a novel chemiluminescent NPs (C NPs) as a nanophotosensitizer for penetration depth independent PDT in tumour cells and bacteria (Scheme 1). This concise chemiluminescent NPs consisted of luminol and horseradish peroxidase (HRP), which is activated by hydrogen peroxide instead by external photoexcitation. In H₂O₂-rich conditions, C NPs exhibited remarkably enhanced ¹O₂ production compared to the luminol/HRP mixture. Finally, C NPs was demonstrated as a powerful nanophotosensitizer for efficient PDT in tumour cells and bacteria without external photoexcitation, becoming a promising platform for the future design of efficient PDT at high tissue depth.Open in a separate windowScheme 1Schematic illustration of the NPs structure and penetration depth-independent PDT.C NPs were prepared by the self-assembly of PLGA, luminol, HRP, and DSPE-mPEG2000 via a nanoprecipitation method (Scheme 1).¹⁶ The detailed preparation process is presented in the ESI.^† Briefly, the PLGA was dissolved in acetonitrile. Luminol and HRP were dissolved in an aqueous solution, which was then added into the previous PLGA acetonitrile solution. This mixed solution was added dropwise to an aqueous solution of DSPE-PEG2000. After gently stirring for 4 h at room temperature, the remaining organic solvent and free molecules were removed by ultrafiltration. The designed C NPs could be stored in an aqueous solution up to 2 months without any eye-observed precipitation (Fig. 1a), indicating their excellent stability. Transmission electron microscopy (TEM) results reveal the spherical morphology of the C NPs with high monodispersity (Fig. 1b), while dynamic light scattering (DLS) indicated their average hydrodynamic diameter with a value of about 70 nm (Fig. 1c).Open in a separate windowFig. 1(a) Photograph of C NPs in an aqueous solution. (b) TEM image of C NPs. Scale bar: 500 nm. (c) Representative DLS of C NPs.The production of reactive oxygen species (ROS, e.g., ¹O₂) in NPs or luminol (L) + HRP was experimentally confirmed by the photodegradation of anthracene-9,10-diyl-bis-methylmalonate (ADMA) in the presence of H₂O₂ and molecular oxygen.^17,18 After the addition of H₂O₂, the characteristic absorbances (260, 358, 378 and 399 nm) of ADMA dispersed in L + HRP solutions gradually decreased with prolonged time (Fig. 2a), indicating the inefficient production of ¹O₂. In sharp contrast, the absorbance of ADMA decreased remarkably in a mixture of ADMA and NPs after the addition of H₂O₂ (Fig. 2b). This is a solid evidence to illustrate that C NPs can be activated by H₂O₂ rather than external photoexcitation to perform PDT. Notably, within 2 min, the NPs almost totally consumed the AMDA, while the L + HRP only showed negligible consumption (Fig. 2c), which unambiguously demonstrated much more efficient production of ¹O₂ by C NPs. This is reasonable because L and HRP within NPs are close together, which is favourable for chemiluminescence. Despite the origin of ¹O₂ production during the C NP-induced chemiluminescence, the above-mentioned results clearly indicate that C NPs can efficiently produce ¹O₂ under H₂O₂ activation, which shows tremendous potential in vivo PDT in high tissue depth.Open in a separate windowFig. 2The absorption spectra of a C NPs (a) or L + HRP (b) and ADMA mixture before and after addition of H₂O₂. The spectra were obtained every 2 min after addition of H₂O₂. Rapidly decreased characteristic absorbance at 260 nm of ADMA within 2 min confirms the efficient ¹O₂ production of C NPs in the presence of H₂O₂. (c) Kinetic curves of the ADMA consumption of L + HRP and C NPs.To verify the PDT effects, we utilized calcein-AM (living cell) and propidium iodide (PI, dead cell) cell viability kits to distinguish the dead cells from living ones (Fig. 3).^19,20 After incubation with H₂O₂, H₂O₂ + HRP, and H₂O₂ + HRP alone, HeLa cells showed comparable cellular viability to the blank group (control) without any treatments, which demonstrate the resistance of HeLa cells toward H₂O₂, H₂O₂ + HRP, and H₂O₂ + HRP. Without the addition of H₂O₂, both L + HRP and C NP-incubated HeLa cells exhibited negligible cytotoxicity, suggesting low dark-cytotoxicity of L + HRP and C NPs. After the addition of H₂O₂, C NP-incubated HeLa cells exhibited strong cytotoxicity relative to the mixed solution of L + HRP.Open in a separate windowFig. 3Live/dead assay of HeLa cells. Green colour represents live cells, and red colour represents dead cells.Furthermore, we evaluated the antibacterial ability of NPs using Gram-negative bacteria, namely E. coli. As shown in Fig. 4a, all groups treated with C NPs, L + HRP, and H₂O₂ alone showed a tiny difference as compared to the blank group (control) without any treatment, which means that C NPs, L + HRP, and H₂O₂ have no obvious influence on E. coli. After the addition of H₂O₂, a huge decrease in C NPs + H₂O₂ was observed, while only a small decrease in L + HRP + H₂O₂, indicating a stronger antibacterial ability of C NPs. The antibacterial efficiency of NPs + H₂O₂ was determined to be 70% (Fig. 4b), which is approximately 10-fold stronger than L + HRP + H₂O₂ (7%). These results clearly demonstrated the strong antibacterial ability of C NPs.Open in a separate windowFig. 4(a) Colony-forming units (CFU) for E. coli treated with NPs before and after addition of H₂O₂ on LB agar plate. The treated E. coli diluted 10⁰ to 10⁻³, 6 microliters of each dilution were inoculated to solid LB media, the E. coli were grown at 37 °C for 12 h. (b) Antibacterial activity of NPs before and after addition of H₂O₂.In summary, we have fabricated a chemiluminescent organic nanophotosensitizer, namely C NPs, which could be activated by H₂O₂ instead by external photoexcitation. The C NPs show a very strong ¹O₂ generation ability in the presence of H₂O₂. The tumour cells and bacteria explanation clearly demonstrate that C NPs could be used as a powerful nanophotosensitizer for potential penetration depth-independent PDT. Our results provide an attractive platform for the future design of a powerful photosensitizer, which can expand the application scope of PDT.     

Magnetic mesoporous bioactive glass for synergetic use in bone regeneration,hyperthermia treatment,and controlled drug delivery

A combination of chemotherapy with hyperthermia can produce remarkable success in treating advanced cancers. For this purpose, magnetite (Fe₃O₄)-doped mesoporous bioactive glass nanoparticles (Fe₃O₄-MBG NPs) were synthesized by the sol–gel method. Fe₃O₄-MBG NPs were found to possess spherical morphology with a size of approximately 50 ± 10 nm and a uniform pore size of 9 nm. The surface area (309 m² g⁻¹) was sufficient for high drug loading capacity and mitomycin C (Mc), an anticancer drug, was entrapped in the Fe₃O₄-MBG NPs. A variable rate of drug release was observed at different pH values (6.4, 7.4 & 8.4) of the release media. No significant death of normal human fibroblast (NHFB) cells was observed during in vitro analysis and for Mc-Fe₃O₄-MBG NPs considerable inhibitory effects on the viability of cancer cells (MG-63) were observed. When Fe₃O₄-MBG NPs were immersed in simulated body fluid (SBF), hydroxycarbonate apatite (HCA) was formed, as confirmed by XRD and FTIR spectra. A negligible value of coercivity and zero remanence confirms that Fe₃O₄-MBG NPs are superparamagnetic. Fe₃O₄-MBG NPs showed a hyperthermia effect in an alternating magnetic field (AMF), and a rise of 11.5 °C in temperature during the first 6 min, making it suitable for hyperthermia applications. Fe₃O₄-MBG NPs expressed excellent biocompatibility and low cytotoxicity, therefore, they are a safe biomaterial for bone tissue regeneration, drug delivery, and hyperthermia treatment.

A combination of chemotherapy with hyperthermia can produce remarkable success in treating advanced cancers.     

Reduced graphene oxide-mediated synthesis of Mn3O4 nanomaterials for an asymmetric supercapacitor cell

Herein, Mn₃O₄/reduced graphene oxide composites are prepared via a facile solution-phase method for supercapacitor application. Transmission electron microscopy results reveal the uniform distribution of Mn₃O₄ nanoparticles on graphene layers. The morphology of the Mn₃O₄ nanomaterial is changed by introducing the reduced graphene oxide during the preparation process. An asymmetric supercapacitor cell based on the Mn₃O₄/reduced graphene oxide composite with the weight ratio of 1 : 1 exhibits relatively superior charge storage properties with higher specific capacitance and larger energy density compared with those of pure reduced graphene oxide or Mn₃O₄. More importantly, the long-term stability of the composite with more than 90.3% capacitance retention after 10 000 cycles can ensure that the product is widely applied in energy storage devices.

The existence presence of rGO can affect the morphology of an Mn₃O₄/rGO composite, and the asymmetric supercapacitor cell created with this composite exhibits good capacitive performance.     

3D printed interdigitated supercapacitor using reduced graphene oxide-MnOx/Mn3O4 based electrodes

In this study hybrid nanocomposites (HNCs) based on manganese oxides (MnO_x/Mn₃O₄) and reduced graphene oxide (rGO) are synthesized as active electrodes for energy storage devices. Comprehensive structural characterizations demonstrate that the active material is composed of MnO_x/Mn₃O₄ nanorods and nanoparticles embedded in rGO nanosheets. The development of such novel structures is facilitated by the extreme synthesis conditions (high temperatures and pressures) of the liquid-confined plasma plume present in the Laser Ablation Synthesis in Solution (LASiS) technique. Specifically, functional characterizations demonstrate that the performance of the active layer is highly correlated with the MnO_x/Mn₃O₄ to rGO ratio and the morphology of MnO_x/Mn₃O₄ nanostructures in HNCs. To that end, active layer inks comprising HNC samples prepared under optimal laser ablation time windows, when interfaced with a percolated conductive network of electronic grade graphene and carbon nanofibers (CNFs) mixture, indicate superior supercapacitance for functional electrodes fabricated via sequential inkjet printing of the substrate, current collector layer, active material layer, and gel polymer electrolyte layer. Electrochemical characterizations unequivocally reveal that the electrode with the LASiS synthesized MnO_x/Mn₃O₄–rGO composite exhibits significantly higher specific capacitance compared to the ones produced with commercially available Mn₃O₄–graphene NCs. Moreover, the galvanostatic charge–discharge (GCD) experiments with the LASiS synthesized HNCs show a significantly larger charge storage capacity (325 F g⁻¹) in comparison to NCs synthesized with commercially available Mn₃O₄–graphene (189 F g⁻¹). Overall, this study has paved the way for use of LASiS-based synthesized functional material in combination with additive manufacturing techniques for all-printed electronics with superior performance.

LASiS-based HNCs of nanostructured MnO_x/Mn₃O₄.     

Folic acid-conjugated gold nanorod@polypyrrole@Fe3O4 nanocomposites for targeted MR/CT/PA multimodal imaging and chemo-photothermal therapy

Integrating multimodal bioimaging and different therapies into one nanoplatform is a promising strategy for biomedical applications, but remains a great challenge. Herein, we have synthesized a biocompatible folic acid (FA) functionalized gold nanorod@polypyrrole@Fe₃O₄ (GNR@PPy@Fe₃O₄-FA) nanocomposite through a facile method. The conjugated FA has endowed the nanocomposite with the ability to recognize targeted cancer cells. Importantly, the nanocomposite has been successfully utilized for magnetic resonance (MR), computed tomography (CT) and photoacoustic (PA) multimodal imaging. Moreover, the GNR@PPy@Fe₃O₄-DOX nanocomposite shows pH-responsive chemotherapy and enables the integration of photothermal therapy and chemotherapy to achieve superior antitumor efficacy. The GNR@PPy@Fe₃O₄-DOX nanocomposites have a drug release of 23.64%, and the photothermal efficiency of the GNR@PPy@Fe₃O₄ nanocomposites reaches 51.46%. Cell viability decreases to 15.83% and 16.47% because of the combination of chemo-photothermal therapy effects. Moreover, the GNR@PPy@Fe₃O₄-DOX-FA nanocomposite could target cancer cells via folic acid and under a magnetic field. The in vivo multimodal imaging and chemo-photothermal therapy effects showed that the GNR@PPy@Fe₃O₄-DOX-FA nanocomposites are a good contrast and theranostic agent. Thus, this multifunctional nanocomposite could be a promising theranostic platform for cancer diagnosis and therapy.

Folic acid-conjugated gold nanorod@polypyrrole@Fe₃O₄ nanocomposites can be used for targeted MR/CT/PA multimodal imaging and chemo-photothermal therapy.     

In vivo neutron capture therapy of cancer using ultrasmall gadolinium oxide nanoparticles with cancer-targeting ability

Gadolinium neutron capture therapy (GdNCT) is considered as a new promising cancer therapeutic technique. Nevertheless, limited GdNCT applications have been reported so far. In this study, surface-modified ultrasmall gadolinium oxide nanoparticles (UGNPs) with cancer-targeting ability (d_avg = 1.8 nm) were for the first time applied to the in vivo GdNCT of cancer using nude model mice with cancer, primarily because each nanoparticle can deliver hundreds of Gd to the cancer site. For applications, the UGNPs were grafted with polyacrylic acid (PAA) for biocompatibility and colloidal stability, which was then conjugated with cancer-targeting arginylglycylaspartic acid (RGD) (shortly, RGD-PAA-UGNPs). The solution sample was intravenously administered into the tails of nude model mice with cancer. At the time of the maximum accumulation of the RGD-PAA-UGNPs at the cancer site, which was monitored using magnetic resonance imaging, the thermal neutron beam was locally irradiated onto the cancer site and the cancer growth was monitored for 25 days. The cancer growth suppression was observed due to the GdNCT effects of the RGD-PAA-UGNPs, indicating that the surface-modified UGNPs with cancer-targeting ability are potential materials applicable to the in vivo GdNCT of cancer.

A cancer growth suppression was observed due to the GdNCT effects of the RGD-PAA-UGNPs.     

Top-down synthesis of sponge-like Mn3O4 at low temperature

A top-down synthetic method was developed for the fabrication of sponge-like Mn₃O₄ composed of Mn₃O₄ nanocrystals by decomposition of manganese formate at 200 °C. The samples were characterized in terms of their structural and morphological properties by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Brunauer–Emmett–Teller (BET) studies. TEM and SEM images showed that the morphology of sponge-like Mn₃O₄ structures was mostly retained from the morphology of the manganese formate precursor, which was controlled by the solvothermal process. Large sponge-like Mn₃O₄ structures exhibiting crystallographic symmetry were prepared under solvothermal treatment for a long time. The XRD pattern showed that the Mn₃O₄ exhibit a tetragonal hausmannite structure. The results of N₂ adsorption analysis indicated that the sponge-like Mn₃O₄ nanostructures possess high surface area. The possible formation mechanism of Mn₃O₄ nanostructures has been discussed.

Sponge-like Mn₃O₄ structures were prepared at low temperature via a facile top-down method and the formation mechanism has been proposed.     

Novel vinyl-modified RGD conjugated silica nanoparticles based on photo click chemistry for in vivo prostate cancer targeted fluorescence imaging

Molecular imaging is a powerful tool for non-invasive visualization of tumors that plays an important role in their diagnosis and treatment. The specificity of molecular imaging probes for cancer cells is important for accurate tumor visualization, with antibody and polypeptide nanoprobe conjugates having often been used as targeting agents for tumor detection. However, many traditional chemical conjugation methods employ complex conjugation reactions that result in poor efficiency and poor bioactivity. Herein, we describe the use of photo click methodology for the rapid synthesis of nanoprobes comprised of silica nanoparticles functionalized with RGD targeting units (SiO₂@T1-RGDk NPs) (∼80 nm) for in vivo prostate cancer fluorescent imaging applications. These SiO₂@T1-RGDk NPs exhibit a maximum absorption wavelength of 380 nm in their UV absorption spectra with a maximum fluorescence emission wavelength of 550 nm. Confocal immunofluorescent imaging reveal that SiO₂@T1-RGDk NPs exhibit excellent targeting ability for visualizing cancer cells, with in vivo fluorescence imaging intensity in a subcutaneous tumor model of prostate cancer reaching a maxima after 4 h. Biosafety assessments showed that SiO₂@T1-RGDk NPs demonstrate no obvious toxicity in mice, thus demonstrated that these novel NPs may prove to be promising fluorescent imaging agents for the accurate detection and treatment of tumors.

Photo click chemistry has been used to prepare RGD conjugated silica nanoprobe (SiO₂@T1-RGDk NPs) that exhibits excellent tumor targeting ability and negligible toxicity which enables them to be used for the diagnosis and treatment of cancer.     

Magnetically targeted nanoparticles for imaging-guided photothermal therapy of cancer

Over the past several decades, nanocarriers have constituted a vital research area for accurate tumor therapy. Herein, magnetically targeted nanoparticles (IRFes) for photothermal therapy were generated by integrating IR780, a molecule with strong emission and absorption in the NIR spectrum and the ability to produce heat after laser irradiation, with Fe₃O₄ nanoparticles (NPs). These IRFes were guided to the tumor site by the application of an external magnetic field. In particular, the strong NIR absorption of IR780 was used for NIRF imaging, and we also demonstrated effective magnetic targeting for the photothermal ablation of tumors. In vitro cell viability and in vivo antitumor experiments showed that these IRFes can ablate 4T1 cells or transplanted 4T1 cell tumors when exposed to 808 nm laser irradiation and a magnetic field. In vivo experiments showed that IRFes only act on tumors, do not damage other organs and can be used to image tumors. These results demonstrate the enormous potential of local photothermal therapy for cancer under the guidance of external magnetic fields and reveal the prospect for the use of multifunctional nanoparticles in tumor therapy.

Magnetically targeted nanoparticles (IRFes) for photothermal therapy were generated by integrating IR780, a molecule with strong emission and absorption in the NIR spectrum and the ability to produce heat after laser irradiation, with Fe₃O₄ nanoparticles.     

Formation of Mn–Cr mixed oxide nanosheets with enhanced lithium storage properties

Novel carbon-free Mn₂O₃/MnCr₂O₄ hybrid nanosheets are synthesized through thermal decomposition of the facilely co-precipitated Mn–Cr binary hydroxide and a carbonate hybrid precursor. As an anode for lithium-ion batteries, the Mn₂O₃/MnCr₂O₄ electrode delivers a wonderful electrochemical performance, i.e., an enhanced stability of 913 mA h g⁻¹ at a current density of 1 A g⁻¹ after 300 cycles, and an excellent rate performance. The excellent electrochemical performance of the Mn₂O₃/MnCr₂O₄ electrode can be ascribed to the interconnected nanosheets and porous structure, as well as the possible synergistic effects between Mn and Cr mixed oxides.

Novel carbon-free Mn₂O₃/MnCr₂O₄ hybrid nanosheets are synthesized. As an anode for lithium-ion batteries, they deliver a wonderful electrochemical performance.     

H2O2-independent chemodynamic therapy initiated from magnetic iron carbide nanoparticle-assisted artemisinin synergy

Chemodynamic therapy (CDT) is a booming technology that utilizes Fenton reagents to kill tumor cells by transforming intracellular H₂O₂ into reactive oxygen species (ROS), but insufficient endogenous H₂O₂ makes it difficult to attain satisfactory antitumor results. In this article, a H₂O₂-free CDT technique with tumor-specificity is developed by using pH-sensitive magnetic iron carbide nanoparticles (PEG/Fe₂C@Fe₃O₄ NPs) to trigger artemisinin (ART) to in situ form ROS. ART-loaded PEG/Fe₂C@Fe₃O₄ NPs are fabricated for the enormous release of Fe²⁺ ions induced by the acidic conditions of the tumor microenvironment after magnetic-assisted tumor enrichment, which results in the rapid degradation of the PEG/Fe₂C@Fe₃O₄ NPs and release of ART once endocytosed into tumor cells. In situ catalysis reaction between the co-released Fe²⁺ ions and ART generates toxic ROS and then induces apoptosis of tumor cells. Both in vitro and in vivo experiments demonstrate that the efficient Fe-enhanced and tumor-specific CDT efficacy for effective tumor inhibition based on ROS generation. This work provides a new direction to improve CDT efficacy based on H₂O₂-independent ROS generation.

Chemodynamic therapy (CDT) is a booming technology that utilizes Fenton reagents to kill tumor cells by transforming intracellular H₂O₂ into reactive oxygen species (ROS), but insufficient endogenous H₂O₂ makes it difficult to attain satisfactory antitumor results.