Polymer coated gold nanoshells for combinational photochemotherapy of pancreatic cancer with gemcitabine.
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ABSTRACT:
SUBMITTER: Emamzadeh M
PROVIDER: S-EPMC8087785 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Engineered gold nanoparticles (GNPs) have become a useful tool in various therapeutic and diagnostic applications. Uncertainty remains regarding possible impacts of GNPs to the immune system. In this regard, we investigated the interactions of polymer-coated GNPs with B cells and their functions in mice as they constitute a crucial part of the immune system and represent a potential target for systemically administered GNPs. Surprisingly, we observed that polymer-coated GNPs mainly interact with the recently identified subpopulation of B lymphocytes named Age-associated B cells (ABCs). Importantly, we also showed that GNPs did not affect the percentages of other B cell populations in different organs. Furthermore, GNPs did not activate B cell innate-like immune responses in any of the tested conditions, nor did they impair adaptive B cell responses in immunized mice. Together, these data provide an important contribution to otherwise limited knowledge about GNP interference with B cell immune function, and demonstrate that GNPs represent a safe tool to target ABCs in vivo for various potential applications.
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Project description:A "smart" core@shell composite nanoparticle (NP) having dual-response mechanisms (i.e., temperature and light) was synthesized, and its efficacy in the loading and release of small molecules was explored. These core@shell NPs are composed of an optically active gold nanoshell (GNS) core and a mesoporous (m-) silica layer (m-SiO2). The GNS@m-SiO2 nanoparticles are further encapsulated within a thermo-responsive poly(N-isopropylacrylamide-co-acrylic acid) hydrogel (PNIPAM-co-AA). The multi-responsive composite NPs were designed to create thermally and optically modulated drug-delivery vehicles with a m-SiO2 layer providing additional non-collapsible space for drug storage. The influence of the m-SiO2 layer on the efficacy of loading and release of methylene blue, which serves as a model for a small-molecule therapeutic drug, was evaluated. The "smart" core@shell composite NPs having a m-SiO2 layer demonstrated an improved capacity to load and release small molecules compared to the corresponding NPs with no m-SiO2 shell. Additionally, an efficient response by the composite NPs was successfully induced by the thermal energy generated from the gold nanoshell core upon exposure to near infrared (NIR) stimulation.
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Project description:Nanoshells made of a silica core and a gold shell possess an optical response that is sensitive to nanometer-scale variations in shell thickness. The exponential red shift of the plasmon resonance with decreasing shell thickness makes ultrathin nanoshells (less than 10 nm) particularly interesting for broad and tuneable ranges of optical properties. Nanoshells are generally synthesised by coating gold onto seed-covered silica particles, producing continuous shells with a lower limit of 15 nm, due to an inhomogeneous droplet formation on the silica surface during the seed regrowth. In this paper, we investigate the effects of three variations of the synthesis protocol to favour ultrathin nanoshells: seed density, polymer additives and microwave treatment. We first maximised gold seed density around the silica core, but surprisingly its effect is limited. However, we found that the addition of polyvinylpyrrolidone during the shell synthesis leads to higher homogeneity and a thinner shell and that a post-synthetic thermal treatment using microwaves can further smooth the particle surface. This study brings new insights into the synthesis of metallic nanoshells, pushing the limits of ultrathin shell synthesis.
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Project description:This article details the preparation of hollow gold-silver nanoshells (GS-NSs) coated with tunably thin silica shells for use in plasmon-enhanced photocatalytic applications. Hollow GS-NSs were synthesized via the galvanic replacement of silver nanoparticles. The localized surface plasmon resonance (LSPR) peaks of the GS-NSs were tuned over the range of visible light to near-infrared (NIR) wavelengths by adjusting the ratio of silver nanoparticles to gold salt solution to obtain three distinct types of GS-NSs with LSPR peaks centered near 500, 700, and 900 nm. Varying concentrations of (3-aminopropyl)trimethoxysilane and sodium silicate solution afforded silica shell coatings of controllable thicknesses on the GS-NS cores. For each type of GS-NS, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images verified our ability to grow thin silica shells having three different thicknesses of silica shell (~2, ~10, and ~15 nm) on the GS-NS cores. Additionally, energy-dispersive X-ray (EDX) spectra confirmed the successful coating of the GS-NSs with SiO2 shells having controlled thicknesses. Extinction spectra of the as-prepared nanoparticles indicated that the silica shell has a minimal effect on the LSPR peak of the gold-silver nanoshells.
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Project description:BackgroundEngineered inorganic nanoparticles (NPs) are essential components in the development of nanotechnologies. For applications in nanomedicine, particles need to be functionalized to ensure a good dispersibility in biological fluids. In many cases however, functionalization is not sufficient: the particles become either coated by a corona of serum proteins or precipitate out of the solvent. We show that by changing the coating of magnetic iron oxide NPs using poly-L-lysine (PLL) polymer the colloidal stability of the dispersion is improved in aqueous solutions including water, phosphate buffered saline (PBS), PBS with 10% fetal bovine serum (FBS) and cell culture medium, and the internalization of the NPs toward living mammalian cells is profoundly affected.MethodsA multifunctional magnetic NP is designed to perform a near-infrared (NIR)-responsive remote control photothermal ablation for the treatment of breast cancer. In contrast to the previously reported studies of gold (Au) magnetic (Fe3O4) core-shell NPs, a Janus-like nanostructure is synthesized with Fe3O4 NPs decorated with Au resulting in an approximate size of 60 nm mean diameter. The surface of trisoctahedral Au-Fe3O4 NPs was coated with a positively charged polymer, PLL to deliver the NPs inside cells. The PLL-Au-Fe3O4 NPs were characterized by transmission electron microscopy (TEM), XRD, FT-IR and dynamic light scattering (DLS). The unique properties of both Au surface plasmon resonance and superparamagnetic moment result in a multimodal platform for use as a nanothermal ablator and also as a magnetic resonance imaging (MRI) contrast agent, respectively. Taking advantage of the photothermal therapy, PLL-Au-Fe3O4 NPs were incubated with BT-474 and MDA-MB-231 breast cancer cells, investigated for the cytotoxicity and intracellular uptake, and remotely triggered by a NIR laser of ~ 808 nm (1 W/cm2 for 10 min).ResultsThe PLL coating increased the colloidal stability and robustness of Au-Fe3O4 NPs (PLL-Au-Fe3O4) in biological media including cell culture medium, PBS and PBS with 10% fetal bovine serum. It is revealed that no significant (< 10%) cytotoxicity was induced by PLL-Au-Fe3O4 NPs itself in BT-474 and MDA-MB-231 cells at concentrations up to 100 μg/ml. Brightfield microscopy, fluorescence microscopy and TEM showed significant uptake of PLL-Au-Fe3O4 NPs by BT-474 and MDA-MB-231 cells. The cells exhibited 40 and 60% inhibition in BT-474 and MDA-MB-231 cell growth, respectively following the internalized NPs were triggered by a photothermal laser using 100 μg/ml PLL-Au-Fe3O4 NPs. The control cells treated with NPs but without laser showed < 10% cell death compared to no laser treatment control CONCLUSION: Combined together, the results demonstrate a new polymer gold superparamagnetic nanostructure that integrates both diagnostics function and photothermal ablation of tumors into a single multimodal nanoplatform exhibiting a significant cancer cell death.
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Project description:Polymer-coated gold nanoparticles target Age-Associated B cells in vivo
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