Search Results (16)

Nanogels are polymer-based, crosslinked hydrogel particles on the nanometer scale. Nanogels developed from synthetic and natural polymers have gathered a great deal of attention in industry and scientific society due to having an increased surface area, softness, flexibility, absorption, and drug loading ability, as well as their mimicking the environment of a tissue. Nanogels having biocompatibility, nontoxic and biodegradable properties with exceptional design, fabrication, and coating facilities may be used for a variety of different biomedical applications, such as drug delivery and therapy, tissue engineering, and bioimaging. Nanogels fabricated by chemical crosslinking and physical self-assembly displayed the ability to encapsulate therapeutics, including hydrophobic, hydrophilic, and small molecules, proteins, peptides, RNA and DNA sequences, and even ultrasmall nanoparticles within their three-dimensional polymer networks. One of the many drug delivery methods being investigated as a practical option for targeted delivery of drugs for cancer treatment is nanogels. The delivery of DNA and anticancer drugs like doxorubicin, epirubicin, and paclitaxel has been eased by polymeric nanogels. Stimuli-responsive PEGylated nanogels have been reported as smart nanomedicines for cancer diagnostics and therapy. Another promising biomedical application of nanogels is wound healing. Wounds are injuries to living tissue caused by a cut, blow, or other impact. There are numerous nanogels having different polymer compositions that have been reported to enhance the wound healing process, such as hyaluronan, poly-L-lysine, and berberine. When antimicrobial resistance is present, wound healing becomes a complicated process. Researchers are looking for novel alternative approaches, as foreign microorganisms in wounds are becoming resistant to antibiotics. Silver nanogels have been reported as a popular antimicrobial choice, as silver has been used as an antimicrobial throughout a prolonged period. Lignin-incorporated nanogels and lidocaine nanogels have also been reported as an antioxidant wound-dressing material that can aid in wound healing. In this review, we will summarize recent progress in biomedical applications for various nanogels, with a prime focus on cancer and wound healing. Full article

Recently, gold nanoclusters (AuNCs) have been widely used in biological applications due to their ultrasmall size, ranging within a few nanometers; large specific surface area; easy functionalization; unique fluorescence properties; and excellent conductivity. However, because they are unstable in solution, AuNCs require stabilization by using ligands such as dendrimers, peptides, DNA, and proteins. As a result, the properties of AuNCs and their formation are determined by the ligand, so the selection of the ligand is important. Of the many ligands implemented, enzyme-stabilized gold nanoclusters (enzyme–AuNCs) have attracted increasing attention for biosensor applications because of the excellent optical/electrochemical properties of AuNCs and the highly target-specific reactions of enzymes. In this review, we explore how enzyme–AuNCs are prepared, their properties, and the various types of enzyme–AuNC-based biosensors that use optical and electrochemical detection techniques. Finally, we discuss the current challenges and prospects of enzyme–AuNCs in biosensing applications. We expect this review to provide interdisciplinary knowledge about the application of enzyme–AuNC-based materials within the biomedical and environmental fields. Full article

We developed a novel site-specific bimodal MRI/fluorescence nanoparticle contrast agent targeting gastrin-releasing peptide receptors (GRPrs), which are overexpressed in aggressive prostate cancers. Biocompatible ultra-small superparamagnetic iron oxide (USPIO) nanoparticles were synthesized using glucose and casein coatings, followed by conjugation with a Cy7.5-K-8AOC-BBN [7-14] peptide conjugate. The resulting USPIO(Cy7.5)-BBN nanoparticles were purified by 100 kDa membrane dialysis and fully characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, and magnetic resonance imaging (MRI) relaxivity, as well as evaluated for in vitro and in vivo binding specificity and imaging efficacy in PC-3 prostate cancer cells and xenografted tumor-bearing mice. The USPIO(Cy7.5)-BBN nanoparticles had a core diameter of 4.93 ± 0.31 nm and a hydrodynamic diameter of 35.56 ± 0.58 nm. The r₂ relaxivity was measured to be 70.2 ± 2.5 s⁻¹ mM⁻¹ at 7T MRI. The Cy7.5-K-8AOC-BBN [7-14] peptide-to-nanoparticle ratio was determined to be 21:1. The in vitro GRPr inhibitory binding (IC₅₀) value was 2.5 ± 0.7 nM, indicating a very high binding affinity of USPIO(Cy7.5)-BBN to the GRPr on PC-3 cells. In vivo MRI showed significant tumor-to-muscle contrast enhancement in the uptake group at 4 h (31.1 ± 3.4%) and 24 h (25.7 ± 2.1%) post-injection compared to the blocking group (4 h: 15.3 ± 2.0% and 24 h: −2.8 ± 6.8%; p < 0.005). In vivo and ex vivo near-infrared fluorescence (NIRF) imaging revealed significantly increased fluorescence in tumors in the uptake group compared to the blocking group. These findings demonstrate the high specificity of bimodal USPIO(Cy7.5)-BBN nanoparticles towards GRPr-expressing PC-3 cells, suggesting their potential for targeted imaging in aggressive prostate cancer. Full article

Cyclic arginyl-glycyl-aspartic acid peptide (cRGD) peptides show a high affinity towards αVβ3 integrin, a receptor overexpressed in many cancers. We aimed to combine the versatility of ultrasmall gold nanoparticles (usGNP) with the target selectivity of cRGD peptide for the directed delivery of a cytotoxic payload in a novel design. usGNPs were synthesized with a modified Brust-Schiffrin method and functionalized via amide coupling and ligand exchange and their uptake, intracellular trafficking, and toxicity were characterized. Our cRGD functionalized usGNPs demonstrated increased cellular uptake by αVβ3 integrin expressing cells, are internalized via clathrin-dependent endocytosis, accumulated in the lysosomes, and when loaded with mertansine led to increased cytotoxicity. Targeting via cRGD functionalization provides a mechanism to improve the efficacy, tolerability, and retention of therapeutic GNPs. Full article

Gold nanoclusters have revealed great potential as nanoantibiotics due to their superior chemical and physical characteristics. In this study, a peptide with 83 amino acids derived from haptoglobin was utilized as a surface ligand to synthesize gold nanoclusters via a facile hydrothermal approach. Characterization of the structural and optical properties demonstrated the successful synthesis of derived haptoglobin-conjugated gold nanoclusters. The spherical derived haptoglobin-conjugated gold nanoclusters exhibited a (111) plane of cubic gold and an ultra-small size of 3.6 ± 0.1 nm. The optical properties such as ultraviolet-visible absorption spectra, X-ray photoelectron spectroscopy spectra, fluorescence spectra, and Fourier transform infrared spectra also validated the successful conjugation between the derived haptoglobin peptide and the gold nanoclusters surface. The antibacterial activity, reactive oxygen species production, and antibacterial mechanisms of derived haptoglobin-conjugated gold nanoclusters were confirmed by culturing the bacterium Escherichia coli with hemoglobin to simulate bacteremia. The surface ligand of the derived haptoglobin peptide of derived haptoglobin-conjugated gold nanoclusters was able to conjugate with hemoglobin to inhibit the growth of Escherichia coli. The derived haptoglobin-conjugated gold nanoclusters with an ultra-small size also induced reactive oxygen species production, which resulted in the death of Escherichia coli. The superior antibacterial activity of derived haptoglobin-conjugated gold nanoclusters can be attributed to the synergistic effect of the surface ligand of the derived haptoglobin peptide and the ultra-small size. Our work demonstrated derived haptoglobin-conjugated gold nanoclusters as a promising nanoantibiotic for combating bacteremia. Full article

Atherosclerosis is the leading cause of global morbidity and mortality. Its therapy requires research in several areas, such as diagnosis of early arteriosclerosis, improvement of the pharmacokinetics and bioavailability of rapamycin as its therapeutic agents. Here, we used the targeting peptide VHPKQHR (VHP) (or fluorescent reagent) to modify the phospholipid molecules to target vascular cell adhesion molecule-1 (VCAM-1) and loaded ultrasmall paramagnetic iron oxide (USPIO/Fe₃O₄) plus rapamycin (Rap) to Rap/Fe₃O₄@VHP-Lipo (VHPKQHR-modified magnetic liposomes coated with Rap). This nanoparticle can be used for both the diagnosis and therapy of early atherosclerosis. We designed both an ex vivo system with mouse aortic endothelial cells (MAECs) and an in vivo system with ApoE knockout mice to test the labeling and delivering potential of Rap/Fe₃O₄@VHP-Lipo with fluorescent microscopy, flow cytometry and MRI. Our results of MRI imaging and fluorescence imaging showed that the T2 relaxation time of the Rap/Fe₃O₄@VHP-Lipo group was reduced by 2.7 times and 1.5 times, and the fluorescence intensity increased by 3.4 times and 2.5 times, respectively, compared with the normal saline group and the control liposome treatment group. It showed that Rap/Fe₃O₄@VHP-Lipo realized the diagnosis of early AS. Additionally, our results showed that, compared with the normal saline and control liposomes treatment group, the aortic fluorescence intensity of the Rap/Fe₃O₄@VHP-Lipo treatment group was significantly weaker, and the T2 relaxation time was prolonged by 8.9 times and 2.0 times, indicating that the targeted diagnostic agent detected the least plaques in the Rap/Fe₃O₄@VHP-Lipo treatment group. Based on our results, the synthesized theragnostic Rap/Fe₃O₄@VHP-Lipo serves as a great label for both MRI and fluorescence bimodal imaging of atherosclerosis. It also has therapeutic effects for the early treatment of atherosclerosis, and it has great potential for early diagnosis and can achieve the same level of therapy with a lower dose of Rap. Full article

The synthesis of ultra-small gold nanoclusters (Au NCs) with sizes down to 2 nm has received increasing interest due to their unique optical and electronic properties. Like many peptide-coated gold nanospheres synthesized before, modified gold nanoclusters with peptide conjugation are potentially significant in biomedical and catalytic fields. Here, we explore whether such small-sized gold nanoclusters can be conjugated with peptides also and characterize them using atomic force microscopy. Using a long and flexible elastin-like polypeptide (ELP)₂₀ as the conjugated peptide, (ELP)₂₀-Au NCs was successfully synthesized via a one-pot synthesis method. The unique optical and electronic properties of gold nanoclusters are still preserved, while a much larger size was obtained as expected due to the peptide conjugation. In addition, a short and rigid peptide (EAAAK)₃ was conjugated to the gold nanoclusters. Their Yong’s modulus was characterized using atomic force microscopy (AFM). Moreover, the coated peptide on the nanoclusters was pulled using AFM-based single molecule-force spectroscopy (SMFS), showing expected properties as one of the first force spectroscopy experiments on peptide-coated nanoclusters. Our results pave the way for further modification of nanoclusters based on the conjugated peptides and show a new method to characterize these materials using AFM-SMFS. Full article

The large size of nanoparticles prevents rapid extravasation from blood vessels and diffusion into tumors. Multimodal imaging uses the physical properties of one modality to validate the results of another. We aim to demonstrate the use of a targeted thin layer-protected ultra-small gold nanoparticles (Au-NPs) to detect cancer in vivo using multimodal imaging with photoacoustic and computed tomography (CT). The thin layer was produced using a mixed thiol-containing short ligands, including MUA, CVVVT-ol, and HS-(CH2)₁₁-PEG₄-OH. The gold nanoparticle was labeled with a heterobivalent (HB) peptide ligand that targets overexpression of epidermal growth factor receptors (EGFR) and ErbB2, hereafter HB-Au-NPs. A human xenograft model of esophageal cancer was used for imaging. HB-Au-NPs show spherical morphology, a core diameter of 4.47 ± 0.8 nm on transmission electron microscopy, and a hydrodynamic diameter of 6.41 ± 0.73 nm on dynamic light scattering. Uptake of HB-Au-NPs was observed only in cancer cells that overexpressed EGFR and ErbB2 using photoacoustic microscopy. Photoacoustic images of tumors in vivo showed peak HB-Au-NPs uptake at 8 h post-injection with systemic clearance by ~48 h. Whole-body images using CT validated specific tumor uptake of HB-Au-NPs in vivo. HB-Au-NPs showed good stability and biocompatibility with fast clearance and contrast-enhancing capability for both photoacoustic and CT imaging. A targeted thin layer-protected gold nanoprobe represents a new platform for molecular imaging and shows promise for early detection and staging of cancer. Full article

Atherosclerosis is a progressive chronic arterial disease characterised by atheromatous plaque formation in the intima of the arterial wall. Several invasive and non-invasive imaging techniques have been developed to detect and characterise atherosclerosis in the vessel wall: anatomic/structural imaging, functional imaging and molecular imaging. In molecular imaging, vascular cell adhesion molecule-1 (VCAM-1) is a promising target for the non-invasive detection of atherosclerosis and for the assessment of novel antiatherogenic treatments. VCAM-1 is an adhesion molecule expressed on the activated endothelial surface that binds leucocyte ligands and therefore promotes leucocyte adhesion and transendothelial migration. Hence, for several years, there has been an increase in molecular imaging methods for detecting VCAM-1 in MRI, PET, SPECT, optical imaging and ultrasound. The use of microparticles of iron oxide (MPIO), ultrasmall superparamagnetic iron oxide (USPIO), microbubbles, echogenic immunoliposomes, peptides, nanobodies and other nanoparticles has been described. However, these approaches have been tested in animal models, and the remaining challenge is bench-to-bedside development and clinical applicability. Full article

Blood-brain barrier (BBB) crossing and brain penetration are really challenging for the delivery of therapeutic agents and imaging probes. The development of new crossing strategies is needed, and a wide range of approaches (invasive or not) have been proposed so far. The receptor-mediated transcytosis is an attractive mechanism, allowing the non-invasive penetration of the BBB. Among available targets, the low-density lipoprotein (LDL) receptor (LDLR) shows favorable characteristics mainly because of the lysosome-bypassed pathway of LDL delivery to the brain, allowing an intact discharge of the carried ligand to the brain targets. The phage display technology was employed to identify a dodecapeptide targeted to the extracellular domain of LDLR (ED-LDLR). This peptide was able to bind the ED-LDLR in the presence of natural ligands and dissociated at acidic pH and in the absence of calcium, in a similar manner as the LDL. In vitro, our peptide was endocytosed by endothelial cells through the caveolae-dependent pathway, proper to the LDLR route in BBB, suggesting the prevention of its lysosomal degradation. The in vivo studies performed by magnetic resonance imaging and fluorescent lifetime imaging suggested the brain penetration of this ED-LDLR-targeted peptide. Full article

Thyroid cancers are the most frequent endocrine cancers and their incidence is increasing worldwide. Thyroid nodules occur in over 19–68% of the population, but only 7–15% of them are diagnosed as malignant. Diagnosis relies on a fine needle aspiration biopsy, which is often inconclusive and about 90% of thyroidectomies are performed for benign lesions. Galectin-1 has been proposed as a confident biomarker for the discrimination of malignant from benign nodules. We previously identified by phage display two peptides (P1 and P7) targeting galectin-1, with the goal of developing imaging probes for non-invasive diagnosis of thyroid cancer. The peptides were coupled to ultra-small superparamagnetic particles of iron oxide (USPIO) or to a near-infrared dye (CF770) for non-invasive detection of galectin-1 expression in a mouse model of papillary thyroid cancer (PTC, as the most frequent one) by magnetic resonance imaging and fluorescence lifetime imaging. The imaging probes functionalized with the two peptides presented comparable image enhancement characteristics. However, those coupled to P7 were more favorable, and showed decreased retention by the liver and spleen (known for their galectin-1 expression) and high sensitivity (75%) and specificity (100%) of PTC detection, which confirm the aptitude of this peptide to discriminate human malignant from benign nodules (80% sensitivity, 100% specificity) previously observed by immunohistochemistry. Full article

To harness the applicability of microribonucleic acid (miRNA) as a cancer biomarker, the detection sensitivity of serum miRNA needs to be improved. This study evaluated the detection sensitivity of miRNA hybridization using cyclic voltammograms (CVs) and microelectrode array chips modified with peptide nucleic acid (PNA) probes and 6-hydroxy-1-hexanethiol. We investigated the PNA probe modification pattern on array chips using fluorescently labeled cDNA. The pattern was not uniformly spread over the working electrode (WE) and had a one-dimensional swirl-like pattern. Accordingly, we established a new ion-channel sensor model wherein the WE is negatively biased through the conductive π–π stacks of the PNA/DNA duplexes. This paper discusses the mechanism underlying the voltage shift in the CV curves based on the electric double-layer capacitance. Additionally, the novel hybridization evaluation parameter ΔE is introduced. Compared to conventional evaluation using oxidation current changes, ΔE was more sensitive. Using ΔE and a new hybridization system for ultrasmall amounts of aqueous solutions (as low as 35 pL), 140 zeptomol label-free miRNA were detected without polymerase chain reaction (PCR) amplification at an adequate sensitivity. Herein, the differences in the target molar amount and molar concentration are elucidated from the viewpoint of hybridization sensitivity. Full article

Pancreatic cancer is a concealed and highly malignant tumor, and its early diagnosis plays an increasingly weighty role during the course of cancer treatment. In this study, we developed a polymeric magnetic resonance imaging (MRI) nanoplatform for MRI contrast agents. To improve tumor-targeting delivery of MRI contrast agents, we employed a pancreatic cancer targeting CKAAKN peptide to prepare a peptide-functionalized amphiphilic hyaluronic acid–vitamin E succinate polymer (CKAAKN–HA–VES) for delivering ultra-small superparamagnetic iron oxide (USPIO), namely, CKAAKN–HA–VES@USPIO. With the modification of the CKAAKN peptide, CKAAKN–HA–VES@USPIO could specifically internalize into CKAAKN-positive BxPC-3 cells. The CKAAKN–HA–VES@USPIO nanoparticles presented a more specific accumulation into pancreatic cancer cells than normal pancreatic cells, and an obvious decrease in signal intensity was observed in CKAAKN-positive BxPC-3 cells, compared with CKAAKN-negative HPDE6-C7 cells and non-targeting HA–VES@USPIO nanoparticles. The results demonstrated that our polymeric MRI nanoplatform could selectively internalize into CKAAKN-positive pancreatic cancer cells by the specific binding of CKAAKN peptide with pancreatic cancer cell membrane receptors, which provided a novel polymeric MRI contrast agent with high specificity for pancreatic cancer diagnosis, and makes it a very promising candidate for magnetic resonance imaging contrast enhancement. Full article

A novel heterogeneous enzyme-palladium (Pd) (0) nanoparticles (PdNPs) bionanohybrid has been synthesized by an efficient, green, and straightforward methodology. A designed Geobacillus thermocatenulatus lipase (GTL) variant genetically and then chemically modified by the introduction of a tailor-made cysteine-containing complementary peptide- was used as the stabilizing and reducing agent for the in situ formation of ultra-small PdNPs nanoparticles embedded on the protein structure. This bionanohybrid was an excellent catalyst in the synthesis of trans-ethyl cinnamate by Heck reaction at 65 °C. It showed the best catalytic performance in dimethylformamide (DMF) containing 10–25% of water as a solvent but was also able to catalyze the reaction in pure DMF or with a higher amount of water as co-solvent. The recyclability and stability were excellent, maintaining more than 90% of catalytic activity after five cycles of use. Full article

It has been proposed that fluctuations in wound pH can give valuable insights into the healing processes in chronic wounds, but acquiring such data can be a technological challenge especially where there is little sample available. Developments in voltammetric pH sensing have opened up new avenues for the design of probes that can function in ultra-small volumes and can be inherently disposable but, as yet few can meet the demands of wound monitoring. A preliminary investigation of the pH response of a new redox wire prepared from a peptide homopolymer of tryptophan is presented and its potential applicability as a sensing material for use in smart dressings is critically discussed. Full article