k-Carrageenan based magnetic@polyelectrolyte complex composite hydrogel for pH and temperature-responsive curcumin delivery.

The dual stimuli-responsive drug delivery system has attracted a lot of interest in controlled drug delivery to specific sites. The magnetic iron oxide nanoparticles integrated polyelectrolyte complex-based hydrogel (MPEC HG) system was developed in this work. First, magnetic nanoparticles were produced in situ in the synthetic polymer polyhexamethylene guanidine (PHMG). Furthermore, the natural biopolymer k-carrageenan (kCG) was employed to form the polyelectrolyte complex (PEC) through charge-balancing interaction between positively charged guanidine units and negatively charged sulfonate groups. Various characterization approaches were used to characterize the developed magnetic polyelectrolyte complex hydrogel (MPEC HG) system. Curcumin (Cur) was employed as a model bioactive agent to examine the drug loading and stimuli-responsive drug release efficiency of the MPEC HG system. Under the combined pH and temperature stimuli conditions (pH 5.0/42 °C), the developed hydrogel system demonstrated great drug loading efficiency (∼ 68 %) and enhanced drug release. Furthermore, the MPEC HG system's in vitro cytotoxicity behavior was investigated on a human liver cancer (HepG2) cell line, and the results revealed that the MPEC HG system is biocompatible. As a result, the MPEC HG system might be used for dual pH and temperature stimuli-responsive drug delivery applications in cancer therapy.

L-lysine Functionalized Mesoporous Silica Hybrid Nanoparticles for pH-Responsive Delivery of Curcumin.

Stimuli-responsive controlled drug delivery systems have attracted the attention of researchers in recent decades due to their potential application in developing efficient drug carriers that are responsive to applied stimuli triggers. In this work, we present the synthesis of L-lysine (an amino acid that combines both amine and carboxylic acid groups in a single unit) modified mesoporous silica nanoparticles (MS@Lys NPs) for the delivery of the anticancer bioactive agent (curcumin, Cur) to cancer cells. To begin, mesoporous silica hybrid nanoparticles (MS@GPTS NPs) with 3-glycidoxypropyl trimethoxy silane (GPTS) were synthesized. The L-lysine groups were then functionalized onto the mesopore channel surfaces of the MS@GPTS NPs through a ring-opening reaction between the epoxy groups of the GPTS and the amine groups of the L-lysine units. Several instrumental techniques were used to examine the structural properties of the prepared L-lysine-modified mesoporous silica nanoparticles (MS@Lys NPs). The drug loading and pH-responsive drug delivery behavior of MS@Lys NPs were studied at different pH levels (pH 7.4, 6.5, and 4.0) using curcumin (Cur) as a model anticancer bioactive agent. The MS@Lys NPs' in vitro cytocompatibility and cell uptake behavior were also examined using MDA-MB-231 cells. The experimental results imply that MS@Lys NPs might be used in cancer therapy as pH-responsive drug delivery applications.

L-Lysine-Modified pNIPAm-co-GMA Copolymer Hydrogel for pH- and Temperature-Responsive Drug Delivery and Fluorescence Imaging Applications.

The development of dual-stimuli-responsive hydrogels attracts much research interest owing to its unique stimuli-responsive characteristics. In this study, a poly-N-isopropyl acrylamide-co-glycidyl methacrylate-based copolymer was synthesized by incorporating N-isopropyl acrylamide (NIPAm) and a glycidyl methacrylate (GMA) monomer. The synthesized copolymer, pNIPAm-co-GMA was further modified with L-lysine (Lys) functional units and further conjugated with fluorescent isothiocyanate (FITC) to produce a fluorescent copolymer pNIPAAm-co-GMA-Lys hydrogel (HG). The in vitro drug loading and dual pH- and temperature-stimuli-responsive drug release behavior of the pNIPAAm-co-GMA-Lys HG was investigated at different pH (pH 7.4, 6.2, and 4.0) and temperature (25 °C, 37 °C, and 45 °C) conditions, respectively, using curcumin (Cur) as a model anticancer drug. The Cur drug-loaded pNIPAAm-co-GMA-Lys/Cur HG showed a relatively slow drug release behavior at a physiological pH (pH 7.4) and low temperature (25 °C) condition, whereas enhanced drug release was achieved at acidic pH (pH 6.2 and 4.0) and higher temperature (37 °C and 45 °C) conditions. Furthermore, the in vitro biocompatibility and intracellular fluorescence imaging were examined using the MDA-MB-231 cell line. Therefore, we demonstrate that the synthesized pNIPAAm-co-GMA-Lys HG system with temperature- and pH-stimuli-responsive features could be promising for various applications in biomedical fields, including drug delivery, gene delivery, tissue engineering, diagnosis, antibacterial/antifouling material, and implantable devices.

Efficient label-free in vivo photoacoustic imaging of melanoma cells using a condensed NIR-I spectral window.

In this paper, we propose an efficient label-free in vivo photoacoustic (PA) imaging of melanoma using a condensed near infrared-I (NIR-I) supercontinuum light source. Although NIR-II spectral window is advantageous such as longer penetration depth compared to the NIR-I region, supercontinuum light sources emitting both NIR-I and NIR-II region could lower the efficiency to target melanoma because of low optical power density in the melanoma's absorption spectra. To exploit efficient in vivo PA imaging of melanoma, we demonstrated the light source emitting from visible (532-600 nm) to NIR-I (600-1000 nm) by optimizing stimulated Raman scattering induced supercontinuum generation. The melanoma's structure is successfully differentiated from blood vessels at a high pulse energy of 2.5 µJ and a flexible pulse repetition rate (PRR) of 5-50 kHz. The proposed light source with the microjoules energies and tens of kHz of PRR can potentially accelerate clinical trials such as early diagnosis of melanoma.

Gating Mechanism of the Voltage-Gated Proton Channel Studied by Molecular Dynamics Simulations.

The voltage-gated proton channel Hv1 has important roles in proton extrusion, pH homeostasis, sperm motility, and cancer progression. The Hv1 channel has also been found to be highly expressed in cell lines and tissue samples from patients with breast cancer. A high-resolution closed-state structure has been reported for the mouse Hv1 chimera channel (mHv1cc), solved by X-ray crystallography, but the open-state structure of Hv1 has not been solved. Since Hv1 is a promising drug target, various groups have proposed open conformations by molecular modeling and simulation studies. However, the gating mechanism and the open-state conformation under the membrane potential are still debate. Here, we present a molecular dynamics study considering membrane potential and pH conditions. The closed-state structure of mHv1cc was used to run molecular dynamics (MD) simulations with respect to electric field and pH conditions in order to investigate the mechanism of proton transfer. We observed a continuous hydrogen bond chain of water molecules called a water-wire to be formed through the channel pore in the channel opening, triggered by downward displacement of the S2 helix and upward movement of the S4 helix relative to other helices. Due to the movement of the S2 and S4 helices, the internal salt bridge network was rearranged, and the hydrophobic gating layers were destroyed. In line with previous experimental and simulation observations, our simulation results led us to propose a new gating mechanism for the Hv1 proton channel, and may provide valuable information for novel drug discovery.

pH and Thermoresponsive PNIPAm-co-Polyacrylamide Hydrogel for Dual Stimuli-Responsive Controlled Drug Delivery.

The therapeutic delivery system with dual stimuli-responsiveness has attracted attention for drug delivery to target sites. In this study, we used free radical polymerization to develop a temperature and pH-responsive poly(N-isopropyl acrylamide)-co-poly(acrylamide) (PNIPAM-co-PAAm). PNIPAm-co-PAAm copolymer by reacting with N-isopropyl acrylamide (NIPAm) and acrylamide (Am) monomers. In addition, the synthesized melamine-glutaraldehyde (Mela-Glu) precursor was used as a cross-linker in the production of the melamine cross-linked PNIPAm-co-PAAm copolymer hydrogel (PNIPAm-co-PAAm-Mela HG) system. The temperature-responsive phase transition characteristics of the resulting PNIPAM-co-PAAm-Mela HG systems were determined. Furthermore, the pH-responsive drug release efficiency of curcumin was investigated under various pH and temperature circumstances. Under the combined pH and temperature stimuli (pH 5.0/45 °C), the PNIPAm-co-PAAm-Mela HG demonstrated substantial drug loading (74%), and nearly complete release of the loaded drug was accomplished in 8 h. Furthermore, the cytocompatibility of the PNIPAm-co-PAAm-Mela HG was evaluated on a human liver cancer cell line (HepG2), and the findings demonstrated that the prepared PNIPAm-co-PAAm-Mela HG is biocompatible. As a result, the PNIPAm-co-PAAm-Mela HG system might be used for both pH and temperature-stimuli-responsive drug delivery.

A portable device with low-power consumption for monitoring mouse vital signs during in vivo photoacoustic imaging and photothermal therapy.

OBJECTIVE: The aim of this study was to monitor the physiological changes and cytotoxic effects of exogenous contrast agents during photoacoustic imaging (PAI) and photothermal therapy (PTT). In this paper, a low-power telemetric device for mouse vital signs monitoring was designed and demonstrated. APPROACH: The power consumption was optimized through hardware and software co-design with a 17% increased operating time compared with typical operation. To demonstrate the feasibility of the monitoring device, PAI and PTT experiments with chitosan-polypyrrole nanocomposites (CS-PPy NCs) as exogenous contrast agents were conducted. Herein, the physiological variation in groups of mice with different CS-PPy NC concentrations was observed and analyzed. MAIN RESULTS: The experimental results indicated the influence of CS-PPy NCs and anesthesia on mouse vital signs in PAI and PTT. Additionally, the association between core temperature, heart rate, and saturation of peripheral oxygen (SpO2) during PAI and PTT was shown. The strong near-infrared absorbance of exogenous contrast agents could account for the increase in mouse core temperature and tumor temperature in this study. Furthermore, high cross-correlation values between core temperature, heart rate, and SpO2 were demonstrated to explain the fluctuation of mouse vital signs during PAI and PTT. SIGNIFICANCE: A design of a vital signs monitoring device, with low power consumption, was introduced in this study. A high cross correlation coefficient of mouse vital signs and the effects of CS-PPy NCs were observed, which explained the mouse physiological variation during the PAI and PTT experiments.

An Up-To-Date Review on Biomedical Applications of Palladium Nanoparticles.

Palladium nanoparticles (PdNPs) have intrinsic features, such as brilliant catalytic, electronic, physical, mechanical, and optical properties, as well as diversity in shape and size. The initial researches proved that PdNPs have impressive potential for the development of novel photothermal agents, photoacoustic agents, antimicrobial/antitumor agents, gene/drug carriers, prodrug activators, and biosensors. However, very few studies have taken the benefit of the unique characteristics of PdNPs for applications in the biomedical field in comparison with other metals like gold, silver, or iron. Thus, this review aims to highlight the potential applications in the biomedical field of PdNPs. From that, the review provides the perceptual vision for the future development of PdNPs in this field.

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.

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.

Photo-based PDT/PTT dual model killing and imaging of cancer cells using phycocyanin-polypyrrole nanoparticles.

Photodynamic therapy (PDT) and photothermal therapy (PTT) using nanoparticles have gained significant attention for its therapeutic effect for cancer treatment. In the present study, we fabricated polypyrrole nanoparticles by employing bovine serum albumin-phycocyanin complex and the formulated particles were stable in various physiological solutions like water, phosphate buffered saline and culture media. The formulated nanoparticles did not cause any noticeable toxicity to MDA-MB-231 and HEK-293 cells. The obtained nanoparticles effectively killed MDA-MB-231 cells in a dual way upon laser illumination, one is through phycocyanin propagated reactive oxygen species (PDT) upon laser illumination and in another way it eradicated the treated cells by converting optical energy into heat energy (PTT). Additionally, the nanoparticles generated good amplitude of ultrasound signals under photoacoustic imaging (PAT) system that facilitates imaging of treated cells. In conclusion, the fabricated particles could be used as a multimodal therapeutic agent for treatment of cancer in the biomedical field.

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-Met­Glu­Pro­Gly­Lys-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 mitogen­activated protein kinase. These results indicated that this Spirulina sp.-derived peptide warrants further investigation as a potential pharmacological inhibitor of ACE and vascular dysfunction.