Bioimaging Of Cancer Cells Research Articles

Carborane Derivative Conjugated with Gold Nanoclusters for Targeted Cancer Cell Imaging.

Polyhedral borane derivatives have been utilized in the treatment of boron neuron capture therapy (BNCT) for brain glioma, and much attention has been paid to search excellent biocompatible boron-rich composites for effective cancer BNCT therapy. In this study, we have exploited the self-assembly of the gold nanoclusters with carborane amino derivatives (GNCs-CB) for the precise bioimaging of cancer cells and targeted delivery of this carborane compound to the tumors. Our observations demonstrate that the GNCs-CB can readily realize accurate tumor imaging and long-term accumulation in tumor sites by EPR effect and nanometer size effect, and thus efficiently implement tumor-targeting delivery of the carborane derivative and facilitate the real-time fluorescent visualization monitoring of the carborane targeted delivery process. This makes it possible to realize the accurate location of the tumor by the carborane derivative and reduce the damage to normal tissues in the process of boron neutron capture therapy through imaging guided treatment.

Rapid and multimodal in vivo bioimaging of cancer cells through in situ biosynthesis of Zn&Fe nanoclusters

Early diagnosis remains highly important for efficient cancer treatment, and hence, there is significant interest in the development of effective imaging strategies. This work reports a new multimodal bioimaging method for accurate and rapid diagnosis of cancer cells by introducing aqueous Fe2+ and Zn2+ ions into cancer cells (i.e., HeLa, U87, and HepG2 cancer cells). We found that the biocompatible metal ions Fe2+ and Zn2+ forced the cancer cells to spontaneously synthesize fluorescent ZnO nanoclusters and magnetic Fe3O4 nanoclusters. These clusters could then be used for multimodal cancer imaging by combining fluorescence imaging with magnetic resonance imaging and computed tomography imaging. Meanwhile, for normal cells (i.e., L02) and tissues, neither fluorescence nor any other obvious difference could be detected between preand post-injection. This multimodal bioimaging strategy based on the in situ biosynthesized Zn&Fe oxide nanoclusters might therefore be useful for early cancer diagnosis and therapy.

Porphyrin-based Pt/Pd-containing metallopolymers: Synthesis, characterization, optical property and potential application in bioimaging

In this work, we report two metallopolymers (Pt-P and Pd-P) through coupling of PtII or PdII porphyrin with fluorene derivatives. The structure and photophysical properties of these two metallpolymers were fully characterized, which indicate that these two metallopolymers are of good capability for bioimaging of cancer cells. Hence, nanoprobes based on Pt-P and Pd-P for bioimaging of HeLa cancer cells were explored. The biological experimental results show that Pt-P NPs exhibit good biocompatibility and specificity to HeLa cancer cells due to its favorable NP size.

Carboxymethylcellulose/ZnCdS fluorescent quantum dot nanoconjugates for cancer cell bioimaging

In this study, it is reported the use of sodium carboxymethyl cellulose (CMCel) as a multifunctional biocompatible polysaccharide for the direct synthesis of fluorescent alloyed-ZnCdS quantum dot (QD) nanoconjugates via aqueous “green” process at room temperature. The nanoconjugates were extensively characterized by spectroscopical (NMR, FTIR, UV-vis, PL) and morphological techniques (DLS, TEM) for accessing their structural and physicochemical properties associated with X-ray photoelectron spectroscopy (XPS) for surface and interface analysis. The results proved the hypothesis of formation of core-shell nanostructures composed by the semiconductor ZnCdS QD core and the organic biocompatible ligand CMCel shell. Moreover, CMCel chemical functional groups played a pivotal role for controlling the size of water-soluble colloidal nanocrystals (2r=4–5nm) and hydrodynamic diameters (<15nm) evidenced by metal complexation and interactions at the nanointerfaces. Additionally, these nanoconjugates were cytocompatible and luminescent for bioimaging human osteosarcoma cancer cells. Thus, these novel polysaccharide-based fluorescent bioconjugates offer promising perspectives as nanoplatforms for cancer cell bioimaging and diagnosis purposes.

Fluorescent pH-Sensing Probe Based on Biorefinery Wood Lignosulfonate and Its Application in Human Cancer Cell Bioimaging.

A water-soluble, ratiometric fluorescent pH probe, L-SRhB, was synthesized via grafting spirolactam Rhodamine B (SRhB) to lignosulfonate (LS). As the ring-opening product of L-SRhB, FL-SRhB was also prepared. The pH-response experiment indicated that L-SRhB showed a rapid response to pH changes from 4.60 to 6.20 with a pKa of 5.35, which indicated that L-SRhB has the potential for pH detection of acidic organelle. In addition, the two probes were internalized successfully by living cells through the endocytosis pathway and could distinguish normal cells from cancer cells by different cell staining rates. In addition, L-SRhB showed obvious cytotoxicity to cancer cells, whereas it was nontoxic to normal cells in the same condition. L-SRhB might have potential in cancer therapy. L-SRhB might be a promising ratiometric fluorescent pH sensor and bioimaging dye for the recognition of cancer cells. The results also provided a new perspective to the high-value utilization of lignin.

Characterization of a near-infrared fluorescent DCPO-tagged glucose analogue for cancer cell imaging

Cancer cells are usually characterized with an increase in glucose uptake when compared with normal cells, which is known as Warburg effect. Near-infrared (NIR) fluorescent glucose analogues have been previously synthesized and been applied in cancer cell imaging. However, most NIR dyes usually have one or more charge in their structures, which may cause low cell membrane permeability and hamper their application in cell imaging. Here we reported a novel glucose analogue N2, which was designed and synthesized based on a new type of NIR dye, DCPO. As expected, higher level of N2 uptake was observed in hepatic carcinoma cells (HepG2) and gastric cancer cells (NCI-N87) than their equivalent cells from normal tissues of the same origin, respectively. The accumulation of N2 in cancer cells was in consistent with the overexpression of glucose transporter GLUT-1 in these cells. The cellular uptake of N2 was then confirmed to be dependent on GLUT-1, which was evidenced by the decreased uptake of N2 in the presence of d-glucose or GLUT-1 inhibitor phloretin. Moreover, uptake of N2 in cancer cells was found to be in a concentration- and time-dependent manner. In all, our study demonstrated that N2, as a novel DCPO-conjugated bioprobe, could be used to monitor cellular glucose consumption, and therefore might be applied in cancer cell bioimaging and bioassay in cancer studies.

Color-Tunable Amphiphilic Segmented π-Conjugated Polymer Nano-Assemblies and Their Bioimaging in Cancer Cells

We report a unique color tunable amphiphilic segmented π-conjugated polymer design and their π-stack driven diverse self-assembled nanostructures and demonstrate their application as a new classes of aqueous luminescent nanoparticle probes for bioimaging in cervical and breast cancer cells. Oligo-phenylenevinylene (OPV) was employed as rigid luminescent π-core and oligo-ethyleneoxy chains were used as flexible spacers to construct new amphiphilic segmented π-conjugated polymers by Witting–Horner polymerization route. The rigidity of the π-core was varied using tricyclodecanemethyleneoxy, 2-ethylhexyloxy or methoxy pendants and appropriate π-core geometry was optimized to achieve maximum aromatic π-stacking interactions. Solvent-induced chain aggregation of the polymers exhibited a morphological transition from one-dimensional helical nanofibrous to three-dimensional spherical nanoassemblies in good/bad solvent combinations. This morphological transformation was accompanied by the fluorescence color change...

Carbon Dots: Large Scale Synthesis of Highly Stable Fluorescent Carbon Dots Using Silica Spheres as Carriers for Targeted Bioimaging of Cancer Cells (Part. Part. Syst. Charact. 10/2015)

Carbon Dots: Large Scale Synthesis of Highly Stable Fluorescent Carbon Dots Using Silica Spheres as Carriers for Targeted Bioimaging of Cancer Cells (Part. Part. Syst. Charact. 10/2015)

Novel in situ biosynthesized fluorescent zinc nanoclusters for specific cellular bio-imaging

Abstract It is well known that zinc ions play an indispensable role in the structure and function of a large number of biological process and relevant bio-macromolecules. When some cancers occurred, the relevant concentration of zinc ions considerably decreased. Since cancer cells have a completely different redox homeostasis from normal cells, in this contribution, we have explored the possibility of bio-imaging or labeling of cancer cells through the in situ biosynthesized zinc nanoclusters by cancerous cells. The results demonstrate that we can readily realize the in vivo fluorescent bio-imaging of cancer cells through the in situ biosynthesis of the biocompatible zinc nanoclusters from cancerous cells ( i.e. , Hela cervical carcinoma cell line and others) when target cells cultured with micromolar zinc gluconate solutions.

Large Scale Synthesis of Highly Stable Fluorescent Carbon Dots Using Silica Spheres as Carriers for Targeted Bioimaging of Cancer Cells

In this paper, fluorescent carbon dots (CDs) loaded on silica (SiO2) spheres are synthesized by the one‐pot hydrothermal route, and then folic acids (FA) are covalently conjugated on the surface of SiO2 spheres. The formed SiO2@CDs‐FA composites can target specific tissues, e.g., cancer. The key of this method is the employment of (3‐aminopropyl)trimethoxysilane as bridge joint, which not only serves as surface passivation agents allowing the large scale synthesis of CDs with high quantum yield, but also enables SiO2@CDs composites further covalent conjugation of FA. The resultant SiO2@CDs composites have many advantages such as easy separation and purification, highly stable, well water‐soluble, and biocompatible. Moreover, the SiO2@CDs‐FA could be used as fluorescent probes for biological imaging in vitro. The uptake of the SiO2@CDs‐FA into HeLa cells is receptor‐mediated endocytosis, which is confirmed by a comparative study using FR‐negative 293T cells. Findings from this study suggest that the SiO2@CDs‐FA composites could be used as a platform for cancer diagnosis studies in various biological systems.

Self-Assembled Hybrids of Fluorescent Carbon Dots and PAMAM Dendrimers for Epirubicin Delivery and Intracellular Imaging.

Advanced nanomaterials integrating imaging and therapeutic modalities on a single platform offers a new horizon in current cancer treatment strategies. Recently, carbon dots (CQDs) have been successfully employed for bioimaging of cancer cells. In the present study, luminescent CQDs with anionic terminus and cationic acetylated G5 poly(amido amine) (G5-Ac85) dendrimers were combined via noncovalent interactions to form self-assembled fluorescent hybrids. The fluorescence of CQDs in hybrids is enhanced in the vicinity of primary amine groups of dendrimers, making them suitable as cellular imaging probes. Encapsulation of chemo-drug epirubicin (EPI) in the dendrimer interiors endowed the fluorescent hybrids with therapeutic potential. The in vitro release of an entrapped EPI drug from CQDs@EPI⊂G5-Ac85 hybrids was faster in an acidic environment than under physiological conditions. Herein, multifunctional CQDs@EPI⊂G5-Ac85 hybrids serve as a dual-emission delivery system, to track the intracellular distribution and cytotoxic effects of EPI drugs. Green emission properties of CQDs were used for fluorescence microscopic imaging and cellular uptake by flow cytometry. Cell cycle analysis, field-emission scanning electron microscopy (FE-SEM), reactive oxygen species (ROS) generation, and up-regulation of apoptotic signaling genes unanimously demonstrated the apoptosis inducing ability of CQDs@EPI⊂G5-Ac85 hybrids in breast cancer (MCF-7) cells. Therefore, we have evaluated CQDs@EPI⊂G5-Ac85 hybrids as prospective candidates to achieve simultaneous imaging and drug delivery in cancer cells.

Graphene oxide-encoded Ag nanoshells with single-particle detection sensitivity towards cancer cell imaging based on SERRS.

Developing ultrasensitive Raman nanoprobes is one of the emerging interests in the field of biosensing and bioimaging. Herein, we constructed a new type of surface-enhanced resonance Raman scattering nanoprobe composed of an Ag nanoshell as a surface-enhanced Raman scattering-active nanostructure, which was encapsulated with 4,7,10-trioxa-1,13-tridecanediamine-functionalized graphene oxide as an ultrasensitive Raman reporter exhibiting strong resonance Raman scattering including distinct D and G modes. The designed nanoprobe was able to produce much more intense and simpler Raman signals even at a single particle level than the Ag nanoshell bearing a well-known Raman reporter, which is beneficial for the sensitive detection of a target in a complex biological system. Finally, this ultrasensitive nanoprobe successfully demonstrated its potential for bioimaging of cancer cells using Raman spectroscopy.

Economical and green synthesis of bagasse-derived fluorescent carbon dots for biomedical applications

Carbon quantum dots (CDs) are promising nanomaterials in biomedical, photocatalytical and photoelectronic applications. However, determining how to explore an ideal precursor for a renewable carbon resource is still an interesting challenge. Here, for the first time, we report that renewable wastes of bagasse as a new precursor were prepared for fluorescent CDs by a hydrothermal carbonization (HTC) process. The characterization results show that such bagasse-derived CDs are monodispersed, contain quasi spherical particles with a diameter of about 1.8 nm and exhibit favorable photoluminescence properties, super-high photostability and good dispersibility in water. Most importantly, bagasse-derived CDs have good biocompatibility and can be easily and quickly internalized by living cancer cells; they can also be used for multicolour biolabeling and bioimaging in cancer cells. It is suggested that bagasse-derived CDs might have potential applications in biomedical and photoelectronic fields.

Rational design of biotinylated probes: fluorescent turn-on detection of (strept)avidin and bioimaging in cancer cells.

Two fluorescent probes SPS1 and SPS2 were designed by connecting biotin to an environment-sensitive coumarin fluorophore. Streptavidin and avidin induced dramatical fluorescence changes in both probes. SPS2 has potential in fluorescent imaging of biotin receptor-enriched tumor cells.

Fabrication of Transferrin Functionalized Gold Nanoclusters/Graphene Oxide Nanocomposite for Turn-On Near-Infrared Fluorescent Bioimaging of Cancer Cells and Small Animals

Transferrin (Tf)-functionalized gold nanoclusters (Tf-AuNCs)/graphene oxide (GO) nanocomposite (Tf-AuNCs/GO) was fabricated as a turn-on near-infrared (NIR) fluorescent probe for bioimaging cancer cells and small animals. A one-step approach was developed to prepare Tf-AuNCs via a biomineralization process with Tf as the template. Tf acted not only as a stabilizer and a reducer but also as a functional ligand for targeting the transferrin receptor (TfR). The prepared Tf-AuNCs gave intense NIR fluorescence that can avoid interference from biological media such as tissue autofluorescence and scattering light. The assembly of Tf-AuNCs and GO gave the Tf-AuNCs/GO nanocomposite, a turn-on NIR fluorescent probe with negligible background fluorescence due to the super fluorescence quenching property of GO. The NIR fluorescence of the Tf-AuNCs/GO nanocomposite was effectively restored in the presence of TfR, due to the specific interaction between Tf and TfR and the competition of TfR with the GO for the Tf in Tf-AuNCs/GO composite. The developed turn-on NIR fluorescence probe offered excellent water solubility, stability, and biocompatibility, and exhibited high specificity to TfR with negligible cytotoxicity. The probe was successfully applied for turn-on fluorescent bioimaging of cancer cells and small animals.

In situ labeling and imaging of cellular protein via a bi-functional anticancer aptamer and its fluorescent ligand

In this article, we reported a novel approach for in situ labeling and imaging HeLa cancer cells utilizing a bifunctional aptamer (AS1411) and its fluorescent ligand, protoporphyrin IX (PPIX). In the presence of potassium ion, AS1411 folded to G-quadruplex structure, binded fluorescent ligand (PPIX) with fluorescent enhancement, and targeted the nucleolin overexpressed by cancer cells. Consequently, bioimaging of cancer cells specifically were realized by laser scanning confocal microscope. The bioimaging strategy with AS1411–PPIX complex was capable to distinguish HeLa cancer cells from normal cells unambiguously, and fluorescence imaging of cancer cells was also realized in human serum. Moreover, the bioimaging method was very facile, effective and need not any covalent modification. These results illustrated that the useful approach can provide a novel clue for bioimaging based on non-covalent bifunctional aptamer in clinic diagnosis.

Surface functionalization of two-photon dye-doped mesoporous silica nanoparticles with folic acid: cytotoxicity studies with HeLa and MCF-7 cancer cells

Two-photon dye-doped mesoporous silica nanoparticles (NPs) have been conjugated with folic acid (FA) in order to obtain efficient nanotools for bioimaging of cancer cells. The surface of the NPs was first functionalized with 3-aminopropyltriethoxysilane. The amine-covered NPs were subsequently reacted with an activated ester derivative of FA. Cytotoxicity studies performed with MCF7 and HeLa cancer cells demonstrate that these functionalized NPs are much less cytotoxic than the non-functionalized NPs against both cell lines. Unfortunately, the grafting of FA enables the formation of charge transfer complexes between the two-photon dye and FA which leads to quenching of the fluorescence of the NPs. Hence although these NPs cannot be used for biomaging purposes, they offer interesting potentialities if the two-photon dye used can be replaced by a two-photon fluorophore which do not interact with FA or if the interaction between the encapsulated dye and FA can be prevented by using a suitable spacer between the surface and the FA moiety.