RGDS-functionalized polyethylene glycol hydrogel-coated magnetic iron oxide nanoparticles enhance specific intracellular uptake by HeLa cells

The objective of this study was to develop thin, biocompatible, and biofunctional hydrogel-coated small-sized nanoparticles that exhibit favorable stability, viability, and specific cellular uptake. This article reports the coating of magnetic iron oxide nanoparticles (MIONPs) with covalently cross-linked biofunctional polyethylene glycol (PEG) hydrogel. Silanized MIONPs were derivatized with eosin Y, and the covalently cross-linked biofunctional PEG hydrogel coating was achieved via surface-initiated photopolymerization of PEG diacrylate in aqueous solution. The thickness of the PEG hydrogel coating, between 23 and 126 nm, was tuned with laser exposure time. PEG hydrogel-coated MIONPs were further functionalized with the fibronectin-derived arginine-glycine-aspartic acid-serine (RGDS) sequence, in order to achieve a biofunctional PEG hydrogel layer around the nanoparticles. RGDS-bound PEG hydrogel-coated MIONPs showed a 17-fold higher uptake by the human cervical cancer HeLa cell line than that of amine-coated MIONPs. This novel method allows for the coating of MIONPs with nano-thin biofunctional hydrogel layers that may prevent undesirable cell and protein adhesion and may allow for cellular uptake in target tissues in a specific manner. These findings indicate that the further biofunctional PEG hydrogel coating of MIONPs is a promising platform for enhanced specific cell targeting in biomedical imaging and cancer therapy

Development of near-infrared region luminescent N-acetyl-L-cysteine-coated Ag2S quantum dots with differential therapeutic effect

Aim: N-acetyl-L-cysteine (NAC) is a free radical scavenger. We developed NAC-coated Ag2S (NAC-Ag2S) quantum dot (QD) as an optical imaging and therapeutic agent. Materials & methods: QDs were synthesized in water. Their optical imaging potential and toxicity were studied in vitro. Results: NAC-Ag2S QDs have strong emission, that is tunable between 748 and 840 nm, and are stable in biologically relevant media. QDs showed significant differences both in cell internalization and toxicity in vitro. QDs were quite toxic to breast and cervical cancer cells but not to lung derived cells despite the higher uptake. NAC-Ag2S reduces reactive oxygen species (ROS) but causes cell death via DNA damage and apoptosis. Conclusion: NAC-Ag2S QDs are stable and strong signal-generating theranostic agents offering selective therapeutic effects

Structure-property relationships of novel phosphonate-functionalized networks and gels of poly(β-amino esters)

pH sensitivity, biodegradability and high biocompatibility make poly(β-amino esters) (PBAEs) important biomaterials with many potential applications including drug and gene delivery and tissue engineering, where their degradation should be tuned to match tissue regeneration rates. Therefore, we synthesize novel phosphonate-functionalized PBAE macromers, and copolymerize them with polyethylene glycol diacrylate (PEGDA) to produce PBAE networks and gels. Degradation and mechanical properties of gels can be tuned by the chemical structure of phosphonate-functionalized macromer precursors. By changing the structure of the PBAE macromers, gels with tunable degradations of 5–97% in 2 days are obtained. Swelling of gels before/after degradation is studied, correlating with the PBAE identity. Uniaxial compression tests reveal that the extent of decrease of the gel cross-link density during degradation is much pronounced with increasing amount and hydrophilicity of the PBAE macromers. Degradation products of the gels have no significant cytotoxicity on NIH 3T3 mouse embryonic fibroblast cells

Near-ir emitting cationic silver chalcogenide quantum dots

A novel near-IR emitting cationic silver chalcogenide quantum dot with a mixed coating wherein the coating comprises of at least 2 different types of materials and is capable of luminescence at the desired near IR bandwidth at wavelengths of 800-850 nm. The quantum dot is fabricated via an advantageous single-step, homogeneous, aqueous method at a low temperature resulting a near IR emitting semiconductor quantum dot with high Quantum Yield, high transfection with low toxicity. The quantum dots may be used in medical imaging, tumor detection, drug delivery and labeling as well as in quantum dot sensitized solar cells

Near-IR emitting cationic silver chalcogenide quantum dots

A novel near-IR emitting cationic silver chalcogenide quantum dot with a mixed coating wherein the coating comprises of at least 2 different types of materials and is capable of luminescence at the desired near IR bandwidth at wavelengths of 800-850 nm. The quantum dot is fabricated via an advantageous single-step, homogeneous, aqueous method at a low temperature resulting a near IR emitting semiconductor quantum dot with high Quantum Yield, high transfection with low toxicity. The quantum dots may be used in medical imaging, tumor detection, drug delivery and labeling as well as in quantum dot sensitized solar cells

Near-IR emitting cationic silver chalcogenide quantum dots

A novel near-IR emitting cationic silver chalcogenide quantum dot with a mixed coating wherein the coating comprises of at least 2 different types of materials and is capable of luminescence at the desired near IR bandwidth at wavelengths of 800-850 nm. The quantum dot is fabricated via an advantageous single-step, homogeneous, aqueous method at a low temperature resulting a near IR emitting semiconductor quantum dot with high Quantum Yield, high transfection with low toxicity. The quantum dots may be used in medical imaging, tumor detection, drug delivery and labeling as well as in quantum dot sensitized solar cells

Near-ir emitting cationic silver chalcogenide quantum dots

A novel near-IR emitting cationic silver chalcogenide quantum dot with a mixed coating wherein the coating comprises of at least 2 different types of materials and is capable of luminescence at the desired near IR bandwidth at wavelengths of 800-850 nm. The quantum dot is fabricated via an advantageous single-step, homogeneous, aqueous method at a low temperature resulting a near IR emitting semiconductor quantum dot with high Quantum Yield, high transfection with low toxicity. The quantum dots may be used in medical imaging, tumor detection, drug delivery and labeling as well as in quantum dot sensitized solar cells

Development of Cationic Ag2S NIR Emitting QDs as New Generation of Theranostic Nanoparticles

Quantum dots are semiconducting nanocrystals with diameters between 2-10 nanometers. Strong signal brightness, resistance to photo bleaching, size-tunable emission and large absorption coefficient across a wide spectral range make them powerful agent against conventional organic fluorescence dyes used in bioimaging applications. In addition to their optical imaging ability, quantum dots have multifunctional properties such as functionalization with targeting ligands for site specific delivery and loading with therapeutic drugs, peptides or oligonucleotides for drug and gene delivery applications thanks to their high surface to volume ratio. However, most of the synthesized QD’s emit in the visible region and they contain heavy metals such as Cd, Pb or Hg, which have intrinsic toxicity to living organisms. Ag2S QDs developed in recent years are of great interest with their excellent biocompatibility and strong emission intensity in near infrared region (NIR) of optical spectrum, offering higher photon penetration depth, lower absorption and scattering of light by cellular components and lower auto-fluorescence in the living tissue compared to visible region. Yet, the Ag2S compositions reported are still limited to anionic and PEGylated ones. We have focused on the development of first cationic Ag2S QDs for combined action of optical imaging and gene therapy. Here, we will discuss the synthesis of PEI coated Ag2S QDs, characterization and applications. PEI coating itself usually do not provide luminescent QDs. Yet, combination with small thiolated molecules provide means to tune the emission wavelength and intensity. We will discuss the influence of 2-mercaptopropionic acid and l-cysteine contribution in this formulation. Further we will discuss the effect of the coating composition on surface charge, size and biocompatibility. Optical imaging and gene delivery performance of these particles will be demonstrated as well

Impact of reaction variables and PEI/l-cysteine ratio on the optical properties and cytocompatibility of cationic Ag 2 S quantum dots as NIR bio-imaging probes

Near-infrared emitting semiconductor quantum dots (NIRQDs) are popular fluorescent probes due to better penetration depth and elimination of tissue autofluorescence. Here, we demonstrate one pot aqueous synthesis of cytocompatible, strongly luminescent, cationic Ag2S NIRQDs utilizing a mixed coating composed of branched polyethyleneimine (PEI)-25 kDa and L-cysteine (Cys) as in vitro luminescent tags and in vivo optical imaging agents. Ultrasmall sizes, a clear first excitonic peak in the absorption spectra, relatively narrow emission peaks with maxima between 730 and 775 nm and a Stokes shift less than 100 nm were obtained. Lifetime measurements indicate excitonic and defect-related emissions. Interestingly, not the emission maxima but the intensity was influenced by the Cys amount more dramatically. PEI/Cys 60/40 mol ratio provided the highest quantum yield reported until now for Ag2S NIRQD (157%) emitting at such a short wavelength. Low molecular weight PEI failed to produce luminescent QDs. Cytotoxicity evaluation of the most strongly luminescing NIRQDs, revealed the PEI/Cys (mol mol−1) 50/50 composition as the non-toxic composition below 2.4 μg Ag per mL concentration. Others had low-toxicity. In vitro microscopy experiments showed endosomal distribution of NIRQDs in Hela cells and strong NIR signal. In vivo imaging study demonstrated that Ag2S NIRQDs could effectively be used as strong optical imaging agents

Redox-responsive phosphonate-functionalized poly (β-amino ester) gels and cryogels

Poly(β-amino ester) networks have gained attention as a class of degradable polymers for biomedical applications, particularly as scaffolds for tissue engineering. In this work, two novel phosphonated diamines (one containing a redox-responsive disulfide group) are reacted with diacrylates via aza-Michael addition reaction to form acrylate terminated poly(β-amino ester)s which are subsequently used as macromolecular precursors for fabrication of degradable gels and cryogels. The degradation rates of the gels and cryogels are monitored in phosphate buffer saline (PBS) and dithiothreitol (DTT), and the degradation times are found to range from hours to months depending on the design of chemical structure. The in vitro cytotoxicities of the degradation products are assessed with mouse embryonic fibroblast cells (NIH 3T3) and human osteosarcoma cells (Saos-2). The tailorability of the degradation rates and the non-toxicity of the degradation products make these poly(β-amino ester) gels and cryogels good candidates as scaffolds for tissue engineering applications