30 research outputs found
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
Synthesis and Characterization of PEGylated Near-IR-Emitting Ag2S Quantum Dots for Tumor Imaging and Therapy
Near-infrared (NIR) emitting semiconductor quantum dots (QDs) have emerged as a new class of fluorescent probes in recent years due to better penetration depth into thetissue and elimination or significant reduction of tissue autofluorescence.Ag2S quantum dots are the most popular NIR emitting quantum dots in recent years becausedramatically improved cytocompatibility compared to heavy metal containing, more traditional QDs such as PbS, PbSe, CdHgTe.Previously, we have developed cationic polyethyleneimine (PEI)-25 kDa and 2MPA coated Ag2S QDs with high quantum yields.However, cationic QDs show some toxicity. Inorder to reduce such toxicity and prevent adsorption of blood components, we pegylated the cationic Ag2S QDs. PEGylation also enabled Doxorubicin® (Dox) loading tothese NIR QDs. Hence, PEG-PEI/2MPA coated aqueous Ag2S NIRQDs showed enhanced cytocompatability, theranostic and diagnostic potential.MaterialsBranched polyethyleneimine (PEI) (Mw 25 kDa) and N,N’-carbonyldiimidazole (CDI) were obtained from Aldrich. Methoxy polyethylene glycol (mPEG-OH, 2 kD) and chloroformwere purchased from Rapp Polymere and Merck Millipore, respectively.MethodsPEI and 2-MPA coated Ag2S QDs have been synthesized according to our previos report [5]. PEGylation was performed using CDI chemistry by activation of hydroxyl terminalgroups of the mPEG with CDI and conjugation of activated mPEG to QDs. Finally, washed samples were loaded with Dox. All cytotoxicity and optical imaging studies wereperformed with HeLa cells.ResultsPEI/2MPA Ag2S QDs have been conjugated with mPEG using CDI chemistry. NMR proved the conjugation. Particles were stable and highly luminescent even after PEGylation(Figure 1 a). Doxorubicin was loaded in PEGylated particles in high efficiency (Figure 1b). PEGylation improved the viability of HeLa cells especially at high doses (Figure 1c).Yet, Dox reduced viability.DiscussionIn this study, PEI and 2MPA coated and PEGylated Ag2S QDs have been developed as new theranostic nanoparticles which allows optical imaging at the NIR window andeffective delivery of a cancer drug into cells. Particles were stable in aqueous medium and luminesce strongly around 820 nm. Dox which is mostly used cancer drug wasloaded to the PEGylated particles to evaluate the QDs as a cancer drug delivery agent. In addition to increased viability of cells after PEGylation, Dox loading increased thetoxicty, provin g effcient delivery of Dox into the cells which was confirmed by confocal microscopy (Figure 1d). The drug release and apoptosis/necrosis studies will beperformed as next steps.ConclusionAs a conclusion, we have developed PEGylated cationic Ag2S QDs with high stability and strong luminesence in the NIR region. Such particles have high cytocompatability tobe used as safe optical imaging and drug delivery agents. This was demonstrated with Dox loading and delivery into HeLa cells.Figure 1. Photoluminescence and absorbance spectra of PEI/2MPA and PEG-PEI/2MPA Ag2S QDs (a), fluorescence intensity of Dox loaded PEG-QDs (b), cytotoxicityevaluation (c) and cell internalization of the nanoparticles (Arrows and red color show PEG-QDs in the HeLa cells) (d)
Synthesis and Characterization of PEGylated Near-IR-Emitting Ag2S Quantum Dots for Tumor Imaging and Therapy
Near-infrared (NIR) emitting semiconductor quantum dots (QDs) have emerged as a new class of fluorescent probes in recent years due to better penetration depth into thetissue and elimination or significant reduction of tissue autofluorescence.Ag2S quantum dots are the most popular NIR emitting quantum dots in recent years becausedramatically improved cytocompatibility compared to heavy metal containing, more traditional QDs such as PbS, PbSe, CdHgTe.Previously, we have developed cationic polyethyleneimine (PEI)-25 kDa and 2MPA coated Ag2S QDs with high quantum yields.However, cationic QDs show some toxicity. Inorder to reduce such toxicity and prevent adsorption of blood components, we pegylated the cationic Ag2S QDs. PEGylation also enabled Doxorubicin® (Dox) loading tothese NIR QDs. Hence, PEG-PEI/2MPA coated aqueous Ag2S NIRQDs showed enhanced cytocompatability, theranostic and diagnostic potential.MaterialsBranched polyethyleneimine (PEI) (Mw 25 kDa) and N,N’-carbonyldiimidazole (CDI) were obtained from Aldrich. Methoxy polyethylene glycol (mPEG-OH, 2 kD) and chloroformwere purchased from Rapp Polymere and Merck Millipore, respectively.MethodsPEI and 2-MPA coated Ag2S QDs have been synthesized according to our previos report [5]. PEGylation was performed using CDI chemistry by activation of hydroxyl terminalgroups of the mPEG with CDI and conjugation of activated mPEG to QDs. Finally, washed samples were loaded with Dox. All cytotoxicity and optical imaging studies wereperformed with HeLa cells.ResultsPEI/2MPA Ag2S QDs have been conjugated with mPEG using CDI chemistry. NMR proved the conjugation. Particles were stable and highly luminescent even after PEGylation(Figure 1 a). Doxorubicin was loaded in PEGylated particles in high efficiency (Figure 1b). PEGylation improved the viability of HeLa cells especially at high doses (Figure 1c).Yet, Dox reduced viability.DiscussionIn this study, PEI and 2MPA coated and PEGylated Ag2S QDs have been developed as new theranostic nanoparticles which allows optical imaging at the NIR window andeffective delivery of a cancer drug into cells. Particles were stable in aqueous medium and luminesce strongly around 820 nm. Dox which is mostly used cancer drug wasloaded to the PEGylated particles to evaluate the QDs as a cancer drug delivery agent. In addition to increased viability of cells after PEGylation, Dox loading increased thetoxicty, provin g effcient delivery of Dox into the cells which was confirmed by confocal microscopy (Figure 1d). The drug release and apoptosis/necrosis studies will beperformed as next steps.ConclusionAs a conclusion, we have developed PEGylated cationic Ag2S QDs with high stability and strong luminesence in the NIR region. Such particles have high cytocompatability tobe used as safe optical imaging and drug delivery agents. This was demonstrated with Dox loading and delivery into HeLa cells.Figure 1. Photoluminescence and absorbance spectra of PEI/2MPA and PEG-PEI/2MPA Ag2S QDs (a), fluorescence intensity of Dox loaded PEG-QDs (b), cytotoxicityevaluation (c) and cell internalization of the nanoparticles (Arrows and red color show PEG-QDs in the HeLa cells) (d)
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