Thi Tuong Vy Phan

Synthesis of amine-polyglycidol functionalised Fe3O4@SiO2 nanocomposites for magnetic hyperthermia, pH-responsive drug delivery, and bioimaging applications

The combined chemotherapy and thermal therapy is mainly considered in clinical applications in cancer therapy. However, the preparation of multifunctional nanomaterials is an attractive approach for cancer treatment. In this report, we present the synthesis of amine-polyglycidol functional shell modified-silica coated-magnetic iron oxide nanocomposites (Fe3O4@SiO2@APG-F) for a FITC conjugated drug carrier system and/or hyperthermia agent in cancer therapy. The Fe3O4@SiO2@APG-F nanocomposite exhibits superparamagnetic properties with a magnetic saturation value of approximately 17.2 emu g−1. The magnetic hyperthermia experiment shows a very fast temperature increase within a short time (45 °C in 4.5 min) when applying an alternating magnetic field (AMF), which is considered to be an appropriate temperature for the localized hyperthermia treatment in cancer therapy. Further, the fluorescein isothiocyanate (FITC), a model fluoropore, was conjugated with the terminal amine groups of the Fe3O4@SiO2@APG to endow the green fluorescent behavior that may be desirable for biological imaging applications. The Fe3O4@SiO2@APG-F material shows high drug loading efficiency and the MTT assay results evidenced that the synthesised Fe3O4@SiO2@APG-F nanocomposites are biocompatible. The fluorescence microscopic images show the particles can be effectively taken up by cancer cells. Therefore, the FITC conjugated Fe3O4@SiO2@APG-F nanocomposites that possess a magnetic core covered by silica coating, organic APG functional shell, and FITC fluorophore together in a single entity could serve as a good hyperthermia agent, drug delivery carrier, and fluorescent contrast agent for bioimaging. Thus, the Fe3O4@SiO2@APG-F nanocomposite could be considered as a promising material to be used in multimodal cancer therapy.

Multimodal tumor-homing chitosan oligosaccharide-coated biocompatible palladium nanoparticles for photo-based imaging and therapy

Palladium, a near-infrared plasmonic material has been recognized for its use in photothermal therapy as an alternative to gold nanomaterials. However, its potential application has not been explored well in biomedical applications. In the present study, palladium nanoparticles were synthesized and the surface of the particles was successfully modified with chitosan oligosaccharide (COS), which improved the biocompatibility of the particles. More importantly, the particles were functionalized with RGD peptide, which improves particle accumulation in MDA-MB-231 breast cancer cells and results in enhanced photothermal therapeutic effects under an 808-nm laser. The RGD peptide-linked, COS-coated palladium nanoparticles (Pd@COS-RGD) have good biocompatibility, water dispersity, and colloidal and physiological stability. They destroy the tumor effectively under 808-nm laser illumination at 2 W cm−2 power density. Further, Pd@COS-RGD gives good amplitude of photoacoustic signals, which facilitates the imaging of tumor tissues using a non-invasive photoacoustic tomography system. Finally, the fabricated Pd@COS-RGD acts as an ideal nanotheranostic agent for enhanced imaging and therapy of tumors using a non-invasive near-infrared laser.

Synthesis of urea-pyridyl ligand functionalized mesoporous silica hybrid material for hydrophobic and hydrophilic drug delivery application

In this work, we propose the synthesis of urea-pyridyl (UPy) ligand functionalized mesoporous silica hybrid material as novel and effective drug delivery system for loading/release of both hydrophobic and hydrophilic drugs. For the synthesis of UPy ligand functionalized mesoporous silica hybrid material, the combination of sol–gel co-condensation technique and post silica surface modification method were adapted. The prepared UPy ligand functionalized mesoporous silica hybrid (UPy-MSH) material was characterized by X-ray diffraction, Fourier-transform infrared, N2 adsorption–desorption analysis. The material morphology and mesopore channels were observed by scanning and transmission electron microscopic analyses. The content of modified organic ligand functionalities present in the UPy-MSH material surface was determined by thermogravimetric analysis. The hydrophilic anticancer drug, 5-Fluorouracil and the hydrophobic anti-inflammatory drug, Ibuprofen was used as a model drugs to determine the loading and pH-responsive release efficiency of the synthesized UPy-MSH material under different pH (pH 7.4 and 5.0) conditions, respectively. In addition, the biocompatibility of the UPy-MSH material was evaluated on MDA-MB-231 cells. The experimental results depicted that the synthesized UPy-MSH material is biocompatible and has high drug loading capacity, selective and controlled release of specific drug with respect to the pH condition.

Polypyrrole–methylene blue nanoparticles as a single multifunctional nanoplatform for near-infrared photo-induced therapy and photoacoustic imaging

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has recently gained much attention due to its selective and localized therapeutic effects by light irradiation. The reagents for phototherapy should have a large absorption coefficient in the near infrared region (NIR) (700 to 2500 nm) to maximize the depth of light penetration in tissues. In this study, we designed multifunctional nanoparticles that can provide strong NIR absorbing capability for the combined treatment of PTT and PDT. For the first time, FDA-approved photosensitizer methylene blue (MB) was conjugated with photothermal material polypyrrole (PPy) to form a novel NIR photo-absorber. The obtained PPy–MB NPs with an average size of 48.5 nm showed excellent biocompatibility, photothermal stability, and high NIR absorbance for the combined PTT and PDT. Under a NIR laser (e.g., 808 nm laser) at 0.5 W cm−2, the temperature of the aqueous solution containing 50 μg ml−1 PPy–MB NPs reached up to 50 °C within a very short time and reactive oxygen species (ROS) were also generated. In vitro investigation confirmed the effectiveness of the PPy–MB NPs in killing the cancer cells under the NIR laser. Further, the phantom test of photoacoustic microscopy (PAM) used in conjunction with PPy–MB NPs showed a strong photoacoustic signal. Therefore, the novel PPy–MB NPs could be considered as promising single multifunctional nanoplatforms for further applications of photo-induced therapy and biomedical imaging.

Biocompatible Chitosan Oligosaccharide Modified Gold Nanorods as Highly Effective Photothermal Agents for Ablation of Breast Cancer Cells

Photothermal therapy (PTT) using biocompatible nanomaterials have recently attracted much attention as a novel candidate technique for cancer therapy. In this work we report the performance of newly synthesized multidentate chitosan oligosaccharide modified gold nanorods (AuNRs-LA-COS) as novel agents for PTT of cancer cells due to their excellent biocompatibility, photothermal stability, and high absorption in the near-infrared (NIR) region. The AuNRs-LA-COS exhibit a strong NIR absorption peak at 838 nm with a mean length of 26 ± 3.1 nm and diameter of 6.8 ± 1.7 nm, respectively. The temperature of AuNRs-LA-COS rapidly reached 52.6 °C for 5 min of NIR laser irradiation at 2 W/cm2. The AuNRs-LA-COS had very low cytotoxicity and exhibited high efficiency for the ablation of breast cancer cells in vitro. The tumor-bearing mice were completely ablated without tumor recurrence after photothermal treatment with AuNRs-LA-COS (25 µg/mL) under laser irradiation. In summary, this study demonstrated that AuNRs-LA-COS with laser irradiation as novel agents pave an alternative way for breast cancer therapy and hold great promise for clinical trials in the near future.

Synthesis and In Vitro Performance of Polypyrrole-Coated Iron–Platinum Nanoparticles for Photothermal Therapy and Photoacoustic Imaging

Multifunctional nano-platform for the combination of photo-based therapy and photoacoustic imaging (PAI) for cancer treatment has recently attracted much attention to nanotechnology development. In this study, we developed iron–platinum nanoparticles (FePt NPs) with the polypyrrole (PPy) coating as novel agents for combined photothermal therapy (PTT) and PAI. The obtained PPy-coated FePt NPs (FePt@PPy NPs) showed excellent biocompatibility, photothermal stability, and high near-infrared (NIR) absorbance for the combination of PTT and PAI. In vitro investigation experimentally demonstrated the effectiveness of FePt@PPy NPs in killing cancer cells with NIR laser irradiation. Moreover, the phantom test of PAI used in conjunction with FePt@PPy NPs showed a strong photoacoustic signal. Thus, the novel FePt@PPy NPs could be considered as promising multifunctional nanoparticles for further applications of photo-based diagnosis and treatment.

A heptameric peptide purified from Spirulina sp. gastrointestinal hydrolysate inhibits angiotensin I-converting enzyme- and angiotensin II-induced vascular dysfunction in human endothelial cells

In this study, a marine microalga Spirulina sp.-derived protein was hydrolyzed using gastrointestinal enzymes to produce an angiotensin I (Ang I)-converting enzyme (ACE) inhibitory peptide. Following consecutive purification, the potent ACE inhibitory peptide was composed of 7 amino acids, Thr-Met-Glu-Pro-Gly-Lys-Pro (molecular weight, 759 Da). Analysis using the Lineweaver-Burk plot and molecular modeling suggested that the purified peptide acted as a mixed non-competitive inhibitor of ACE. The inhibitory effects of the peptide against the cellular production of vascular dysfunction-related factors induced by Ang II were also investigated. In human endothelial cells, the Ang II-induced production of nitric oxide and reactive oxygen species was inhibited, and the expression of inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1) was downregulated when the cells were cultured with the purified peptide. Moreover, the peptide blocked the activation of p38 mitogen-activated protein kinase. These results indicated that this Spirulina sp.-derived peptide warrants further investigation as a potential pharmacological inhibitor of ACE and vascular dysfunction.

Photoacoustic Imaging-Guided Photothermal Therapy with Tumor-Targeting HA-FeOOH@PPy Nanorods

Cancer theragnosis agents with both cancer diagnosis and therapy abilities would be the next generation of cancer treatment. Recently, nanomaterials with strong absorption in near-infrared (NIR) region have been explored as promising cancer theragnosis agents for bio-imaging and photothermal therapy (PTT). Herein, we reported the synthesis and application of a novel multifunctional theranostic nanoagent based on hyaluronan (HA)-coated FeOOH@polypyrrole (FeOOH@PPy) nanorods (HA-FeOOH@PPy NRs) for photoacoustic imaging (PAI)-guided PTT. The nanoparticles were intentionally designed with rod-like shape and conjugated with tumor-targeting ligands to enhance the accumulation and achieve the entire tumor distribution of nanoparticles. The prepared HA-FeOOH@PPy NRs showed excellent biocompatible and physiological stabilities in different media. Importantly, HA-FeOOH@PPy NRs exhibited strong NIR absorbance, remarkable photothermal conversion capability, and conversion stability. Furthermore, HA-FeOOH@PPy NRs could act as strong contrast agents to enhance PAI, conducting accurate locating of cancerous tissue, as well as precise guidance for PTT. The in vitro and in vivo photothermal anticancer activity results of the designed nanoparticles evidenced their promising potential in cancer treatment. The tumor-bearing mice completely recovered after 17 days of PTT treatment without obvious side effects. Thus, our work highlights the great potential of using HA-FeOOH@PPy NRs as a theranostic nanoplatform for cancer imaging-guided therapy.

Chitosan oligosaccharide coated mesoporous silica nanoparticles for pH-stimuli responsive drug delivery applications

Biopolymer-coated drug delivery system with high drug-loading efficiency and pH-stimuli responsive drug release to the target site receives much research interest in cancer therapy. In this study, we have synthesized a marine biopolymer, namely chitosan oligosaccharide (COS) coated mesoporous silica nanoparticle (MSNs@COS NPs) system for pH-responsive drug delivery applications. The COS coating onto the silica nanoparticles was performed through metal–ligand complex coordination approaches. The prepared MSNs@COS NPs system were characterized by low-angle X-ray diffraction (XRD), Fourier-transform infrared (FTIR), N2 adsorption–desorption and transmission electron microscopic (TEM), and thermogravimetric analyses. The COS-coated MSNs@COS NPs system shows high drug-loading capacity, good drug retention efficiency under physiological pH (pH 7.4) conditions, and an intracellular pH-responsive drug release behavior under acidic pH (pH 6.5, 5.0, and 4.0) environments. Furthermore, the biocompatibility and the intracellular uptake behavior of the MSNs@COS NPs system were evaluated by using MDA-MB-231 cells. The in vitro cytotoxicity and fluorescence microscopic analysis results evidenced that the synthesized MSNs@COS NPs system is biocompatible and could be readily taken up by MDA-MB-231 cells. Therefore, we believe that the proposed system could be applicable for pH-stimuli responsive controlled drug delivery applications in cancer therapy.

Chitosan as a stabilizer and size-control agent for synthesis of porous flower-shaped palladium nanoparticles and their applications on photo-based therapies

This study reported a newly developed green synthesis method using chitosan and vitamin C to prepare porous flower-shaped palladium nanoparticles. We found that chitosan not only worked as a stabilizer but also as a size-control agent for the synthesis of these nanoparticles. The growth model of flower-shaped palladium nanoparticles was proposed to interpret mechanistic understanding. The obtained nanoparticles showed good biocompatibility and strong near-infrared absorption. The nanoparticles were successfully demonstrated to be highly efficient for both in vitro photothermal therapy and in vitro photoacoustic imaging.