Nano–bio interaction between human immunoglobulin G and nontoxic, near-infrared emitting water-borne silicon quantum dot micelles

In recent years, the field of nanomaterials has exponentially expanded with versatile biological applications. However, one of the roadblocks to their clinical translation is the critical knowledge gap about how the nanomaterials interact with the biological microenvironment (nano–bio interactions). When nanomaterials are used as drug carriers or contrast agents for biological imaging, the nano–bio interaction-mediated protein conformational changes and misfolding could lead to disease-related molecular alterations and/or cell death. Here, we studied the conformation changes of human immunoglobulin G (IgG) upon interaction with silicon quantum dots functionalized with 1-decene, Pluronic-F127 (SiQD-De/F127 micelles) using UV-visible, fluorescence steady state and excited state kinetics, circular dichroism, and molecular modeling. Decene monolayer terminated SiQDs are accumulated inside the Pluronic F127 shells to form SiQD-De/F127 micelles and were shown to bind strongly with IgG. In addition, biological evaluation studies in cell lines (HeLa, Fibroblast) and medaka fish (eggs and larvae) showed enhanced uptake and minimal cytotoxicity. Our results substantiate that engineered QDs obviating the protein conformational changes could have adept bioefficacy

Iodine containing porous organosilica nanoparticles trigger tumor spheroids destruction upon monochromatic X-ray irradiation: DNA breaks and K-edge energy X-ray

アインシュタインの光電効果をがん細胞の中で再現　放射線治療への新展開. 京都大学プレスリリース. 2021-07-14.Quantum physics helps destroy cancer cells. 京都大学プレスリリース. 2021-07-14.X-ray irradiation of high Z elements causes photoelectric effects that include the release of Auger electrons that can induce localized DNA breaks. We have previously established a tumor spheroid-based assay that used gadolinium containing mesoporous silica nanoparticles and synchrotron-generated monochromatic X-rays. In this work, we focused on iodine and synthesized iodine-containing porous organosilica (IPO) nanoparticles. IPO were loaded onto tumor spheroids and the spheroids were irradiated with 33.2 keV monochromatic X-ray. After incubation in CO₂ incubator, destruction of tumor spheroids was observed which was accompanied by apoptosis induction, as determined by the TUNEL assay. By employing the γH2AX assay, we detected double strand DNA cleavages immediately after the irradiation. These results suggest that IPO first generate double strand DNA breaks upon X-ray irradiation followed by apoptosis induction of cancer cells. Use of three different monochromatic X-rays having energy levels of 33.0, 33.2 and 33.4 keV as well as X-rays with 0.1 keV energy intervals showed that the optimum effect of all three events (spheroid destruction, apoptosis induction and generation of double strand DNA breaks) occurred with a 33.2 keV monochromatic X-ray. These results uncover the preferential effect of K-edge energy X-ray for tumor spheroid destruction mediated by iodine containing nanoparticles

Recent advances on fluorescent biomarkers of near-infrared quantum dots for in vitro and in vivo imaging

Luminescence probe has been broadly used for bio-imaging applications. Among them, near-infrared (NIR) quantum dots (QDs) are more attractive due to minimal tissue absorbance and larger penetration depth. Above said reasons allowed whole animal imaging without slice scan or dissection. This review describes in vitro and in vivo imaging of NIR QDs in the regions of 650–900 nm (NIR-I) and 1000–1450 nm (NIR-II). Also, we summarize the recent progress in bio-imaging and discuss the future trends of NIR QDs including group II-VI, IV-VI, I-VI, I-III-VI, III-V, and IV semiconductors

Recent Development to Explore the Use of Biodegradable Periodic Mesoporous Organosilica (BPMO) Nanomaterials for Cancer Therapy

Porous nanomaterials can be used to load various anti-cancer drugs efficiently and deliver them to a particular location in the body with minimal toxicity. Biodegradable periodic mesoporous organosilica nanoparticles (BPMOs) have recently emerged as promising candidates for disease targeting and drug delivery. They have a large functional surface and well-defined pores with a biodegradable organic group framework. Multiple biodegradation methods have been explored, such as the use of redox, pH, enzymatic activity, and light. Various drug delivery systems using BPMO have been developed. This review describes recent advances in the biomedical application of BPMOs

Binding Mode of CpG Oligodeoxynucleotides to Nanoparticles Regulates Bifurcated Cytokine induction via Toll-like Receptor 9

The interaction of cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) with Toll-like receptor 9 (TLR9) activates the immune system. Multimeric class A CpG ODNs induce interferon-α (IFN-α) and, to a lesser extent, interleukin-6. By contrast, monomeric class B CpG ODNs induce interleukin-6 but not IFN-α. This difference suggests that the multimerization of CpG ODN molecules is a key factor in IFN-α induction. We multimerized class B CpG ODN2006x3-PD molecules that consist entirely of a phosphodiester backbone onto quantum dot silicon nanoparticles with various binding modes. Herein, we present the binding mode-dependent bifurcation of cytokine induction and discuss its possible mechanism of CpG ODN and TLR9 interaction. Our discoveries also suggest that nanoparticles play roles in not only delivery of CpG ODNs but also control of CpG ODN activity

Insights into the Binding of 3-(1-Phenylsulfonyl-2-methylindol-3-ylcarbonyl) Propanoic Acid to Bovine Serum Albumin: Spectroscopy and Molecular Modelling Studies

Serum albumin is a globular protein which is most abundant in human that binds remarkably with wide range of drugs. A reliable prediction of protein and drug binding at the atomic level by optical spectroscopy and molecular modeling methods provides the basis for the design of new drug compounds. In the current study, A newly synthesized 3-(1-Phenylsulfonyl-2-methylindol-3- ylcarbonyl) propanoic acid (PA) which has a antifungal and anti bacterial effects also plays vital role for the nutrition, micro biome and physiology triangle. It has been reported that 90% of PA quantity is metabolized by the liver and the rest is transported into the peripheral blood, since PA has binding characteristics, understanding pharmacokinetic mechanism of the drug is important. In this regard, the binding of PA-Bovine Serum Albumin (BSA) was investigated by UV-Vis, fluorescence spectroscopy and molecular docking studies. From the experimental and modeling studies it is observed that PA could bind BSA through the hydrophobic force, and hydrogen bonding. The current study reveals that the optical spectroscopy and molecular modeling techniques could be effectively used to study the design of new drug and understanding their pharmacokinetics

Generation of microgrooved silica nanotube membranes with sustained drug delivery and cell contact guidance ability by using a Teflon microfluidic chip

Silica nanotubes have been extensively applied in the biomedical field. However, very little attention has been paid to the fabrication and application of micropatterned silica nanotubes. In the present study, microgrooved silica nanotube membranes were fabricated in situ by microgrooving silica-coated collagen hybrid fibril hydrogels in a Teflon microfluidic chip followed by calcination for removal of collagen fibrils. Scanning electron microscopy images showed that the resulting silica nanotube membranes displayed a typical microgroove/ridge surface topography with similar to 50 mu m microgroove width and similar to 120 mu m ridge width. They supported adsorption of bone morphogenetic protein 2 (BMP-2) and exhibited a sustained release behavior for BMP-2. After culturing with osteoblast MC3T3-E1 cells, they induced an enhanced osteoblast differentiation due to the release of biologically active BMP-2 and a strong contact guidance ability to directly align and elongate osteoblasts due to the presence of microgrooved surface topography, indicating their potential application as a multi-functional cell-supporting matrix for tissue generation