It is highly desirable in biomedical sciences to utilize the multifunctional nanoparticles of similar size with tunable emission. Since the optoelectronic properties of quantum dots (QDs) originate from size-dependent quantum confinement effects, we developed an alternate approach to synthesize color-tunable CdSe/ZnS QDs based on interfacial ion exchange (predominantly exchange of Se2– by S2– anions), using 1-dodecanethiol and oleylamine solvent systems as a sensitive parameter. The wide-range color-tunability (490–570 nm) was achieved unexpectedly as a result of interfacial alloying without inducing a significant change in the size (from 4.45 to 4.81 nm) of QDs. The local atomic structure order, chemical composition, and nature of alloying in QDs were unraveled by XAFS data analysis. Owing to the molecular-like sensitization behavior, the QDs were evaluated for singlet molecular oxygen (1O2) efficiency. They were further studied in RAW 264.7 macrophages for biocompatibility, bioimaging, and delivering pathways for use in future photodynamic therapy (PDT). The QDs demonstrated efficient singlet molecular oxygen (1O2) quantum yields (ΦQDs) of 14, 12, and 18% for QDs (I), QDs (II), and QDs (III), respectively. The QD-treated cells presented high cell viability above 85% and induced no cell activation. Fluorescence and transmission electron microscopy (TEM) images of cells manifested a considerable amount of QDs in the vicinity of the cell membrane and intracellular regions. The pathway-specific inhibition measurements revealed that the QDs were internalized by cells via energy-dependent endocytosis, predominantly macropinocytosis and other receptor-mediated endocytic pathways, and accumulated them presumably in endosome/lysosomes. This study will open new possibilities for engineering interfacial alloying-based tunable emission QDs and pathway-specific delivery of QD-based theranostics into a site of interest for simultaneous bioimaging and PDT.
Gold nanoparticle (AuNP) bioconjugates have been used as therapeutic and diagnostic tools; however, in vivo biocompatibility and cytotoxicity continue to be two fundamental issues. The effect of AuNPs (20 nm) conjugated with antibody [immunoglobulin G (IgG)], albumin, protein A, PEG4000, and citrate (cit) were evaluated in vitro using primary human cells of the vascular system. AuNP bioconjugates did not cause lysis of human erythrocytes, apoptosis or necrosis of human leukocytes, and endothelial cells in vitro, although AuNPs had been internalized and detected in the cytoplasm. Moreover, the influence of AuNPs on rheological parameters, blood and vessel wall characteristics was investigated in vivo by intravital microscopy assay using male Wistar rats mesentery microcirculation as model. Intravenous injection of AuNP-IgG or cit-AuNP did not cause hemorrhage, hemolysis or thrombus formation, instead suppressed the leukocyte adhesion to postcapillary vessel walls, an early stage of an inflammatory process. Furthermore, AuNP-IgG abrogated the expression of platelet-endothelial cell adhesion molecule-1, chemotaxis, and oxidative burst activation on neutrophils after leukotriene B4 stimulation, a membrane receptor-dependent stimulus, thus confirming their anti-inflammatory effects in vitro. The expression of oxidative burst activation was also suppressed after stimulating AuNP-IgG-treated neutrophils with lipid-soluble phorbol myristate acetate (PMA), confirming the direct intracellular action of AuNP-IgG on the inflammatory process in vitro. Our in vitro and in vivo experimental approaches highlighted the great potentiality of AuNP bioconjugates for therapeutic and diagnostic applications by parenteral routes.
The development of QDs based fluorescence bionanoprobe for cellular imaging fundamentally relies upon the precise knowledge of particle-cell interaction, optical properties of QDs inside and outside of the cell, movement...
The biocompatibility, bionanointeraction, uptake efficiency, and entry pathway of luminescent nanomaterials are the key factors to understand development of an efficient bionanoprobe. The foremost objective of this work is to explore the potential of 3-mercaptopropionic acid (3-MPA) capped ZnSe:xMn 2+ (x = 5, 10, and 15 mol %) quantum dots (QDs) for the development of bionanoprobe used in future biological and clinical applications. For this purpose, highly intense orangeemitting activator Mn 2+ ion doped ZnSe QDs were synthesized via a high-temperature organometallic method and rendered watersoluble by a ligand exchange approach. The morphological and physicochemical characterizations displayed the ultrasmall zincblend cubic crystal structure of QDs with an elliptical shape nanocrystals and average diameter of 4 nm. The luminescent nanomaterials exhibited orange emission centered at 584 nm under excitation at 385 nm. The biocompatibility, time-dependent cellular uptake, and the uptake mechanism of QDs were studied in RAW 264.7 macrophages, accomplished by various cytotoxicity assays, CytoViva hyperspectral enhanced dark-field and dual-mode fluorescence (DMF) microscopy, and transmission electron microscopy (TEM) images. The cytotoxicity study did not confirm any noticeable deleterious effect of QDs within incubation for 6 h. The fluorescence images of cells incubated with QDs showed efficient emission, which is a manifestation that QDs are photochemically stable in the intracellular environment. The cellular uptake findings demonstrated that the QDs were predominantly internalized via clathrin-and caveolae-mediated pathways. After the uptake, QDs aggregates appeared inside the vesicles in the cytoplasm, and their number and size gradually increased as a function of time. Nevertheless, the fluorescent QDs presented remarkable colloidal stability in various media, biocompatibility within the designated time, efficient time-dependent uptake, and distinct entry pathway in RAW macrophages, suggesting promising candidates to explore for the development of future bionanoprobes.
Ranelate ion, the major component of an old antiosporotic drug, exhibits a unusual chemical structure encompassing a thiophene ring with two carboxylic groups, a cyanonitrile substituent, and a nitrile diacetate group; it undergoes decarboxylation at the thiophene carbon‐5 position in acidic solutions, yielding a photoreactive (H5Ran) species which converts into a remarkably stable blue dithiophene dye in the presence of UV light and air.
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