Xueyun Gao

Metallofullerene nanoparticles circumvent tumor resistance to cisplatin by reactivating endocytosis

Cisplatin is a chemotherapeutic drug commonly used in clinics. However, acquired resistance confines its application in chemotherapeutics. To overcome the acquired resistance to cisplatin, it is reasoned, based on our previous findings of mediation of cellular responses by [Gd@C82(OH)22]n nanoparticles, that [Gd@C82(OH)22]n may reverse tumor resistance to cisplatin by reactivating the impaired endocytosis of cisplatin-resistant human prostate cancer (CP-r) cells. Here we report that exposure of the CP-r PC-3-luc cells to cisplatin in the presence of nontoxic [Gd@C82(OH)22]n not only decreased the number of surviving CP-r cells but also inhibited growth of the CP-r tumors in athymic nude mice as measured by both optical and MRI. Labeling the CP-r PC-3 cells with transferrin, an endocytotic marker, demonstrated that pretreatment of the CP-r PC-3-luc cells with [Gd@C82(OH)22]n enhanced intracellular accumulation of cisplatin and formation of cisplatin-DNA adducts by restoring the defective endocytosis of the CP-r cancer cells. The results suggest that [Gd@C82(OH)22]n nanoparticles overcome tumor resistance to cisplatin by increasing its intracellular accumulation through the mechanism of restoring defective endocytosis. The technology can be extended to other challenges related to multidrug resistance often found in cancer treatments.

Bio-distribution and metabolic paths of silica coated CdSeS quantum dots

With the rapid development of quantum dot (QD) technology, water-soluble QDs have the prospect of being used as a biological probe for specific diagnoses, but their biological behaviors in vivo are little known. Our recent in vivo studies concentrated on the bio-kinetics of QDs coated by hydroxyl group modified silica networks (the QDs are 21.3+/-2.0 nm in diameter and have maximal emission at 570 nm). Male ICR mice were intravenously given the water-soluble QDs with a single dose of 5 nmol/mouse. Inductively coupled plasma-mass spectrometry was used to measure the (111)Cd content to indicate the concentration of QDs in plasma, organs, and excretion samples collected at predetermined time intervals. Meanwhile, the distribution and aggregation state of QDs in tissues were also investigated by pathological examination and differential centrifugation. The plasma half-life and clearance of QDs were 19.8+/-3.2 h and 57.3+/-9.2 ml/h/kg, respectively. The liver and kidney were the main target organs for QDs. The QDs metabolized in three paths depending on their distinct aggregated states in vivo. A fraction of free QDs, maintaining their original form, could be filtered by glomerular capillaries and excreted via urine as small molecules within five days. Most QDs bound to protein and aggregated into larger particles that were metabolized in the liver and excreted via feces in vivo. After five days, 8.6% of the injected dose of aggregated QDs still remained in hepatic tissue and it was difficult for this fraction to clear.

Detection of Trace Hg2+ via Induced Circular Dichroism of DNA Wrapped Around Single-Walled Carbon Nanotubes

The strongly induced circular dichroism (ICD) signals of DNA wrapped around single-walled carbon nanotubes (SWCNTs) are shown by the Synchrotron Radiation Facility. In solution, trace amounts of Hg ions have a strong affinity to bind the nucleic bases of DNA-SWCNTs via a pseudo-first-order kinetic reaction. The Hg binding to the bases of DNA results in partial DNA disassociation from the SWCNTs. Such disassociation of DNA from the SWCNTs will decrease the coupling effects of the transition dipole moments between DNA and SWCNTs, thus inducing the ICD signal of DNA-SWCNTs to decrease significantly. Herein, the ICD of DNA-SWCNTs is applied to detect the concentration of Hg ions at nM level.

The suppression of prostate LNCaP cancer cells growth by Selenium nanoparticles through Akt/Mdm2/AR controlled apoptosis

The trace element Selenium is suggested having cancer prevention activity and used as food supplement. Previous results had shown Selenium nanoparticles are safer compared with other Selenium compounds like selenomethionine, sodium selenite and monomethylated Selenium, however, its anticancer activity and intrinsic mechanisms are still elusive. Here, we prepared Selenium nanoparticles and investigated its inherent anticancer mechanisms. We found Selenium nanoparticles inhibit growth of prostate LNCaP cancer cells partially through caspases mediated apoptosis. Selenium nanoparticles suppress transcriptional activity of androgen receptor via down-regulating its mRNA and protein expression. Moreover, Selenium nanoparticles activate Akt kinase by increasing its phosphorylation, promote Akt-dependent androgen receptor phosphorylation and Mdm2 regulated degradation through proteasome pathway. We suggest Selenium nanoparticles suppress prostate cancer cells growth by disrupting androgen receptor, implicating a potential application in cancer treatment.

Serial silver clusters biomineralized by one peptide.

The artificial peptide with amino acid sequence CCYRGRKKRRQRRR was used to biomineralize serial Ag clusters. Under different alkaline conditions, clusters with red and blue emission were biomineralized by the peptide, respectively. The matrix-assisted laser desorption/ionization time-of-flight mass spectra implied that the red-emitting cluster sample was composed of Ag(28), while the blue-emitting cluster sample was composed of Ag(5), Ag(6), and Ag(7). The UV-visible absorption and infrared spectra revealed that the peptide phenol moiety reduced Ag(+) ions and that formed Ag clusters were captured by peptide thiol moieties. The phenol reduction potential was controlled by the alkalinity and played an important role in determining the Ag cluster size. Circular dichroism observations suggested that the alkalinity tuned the peptide secondary structure, which may also affect the Ag cluster size.

Bifunctional peptides that precisely biomineralize Au clusters and specifically stain cell nuclei

A bifunctional peptide containing a domain that targets cell nuclei and a domain with the ability to biomineralize and capture Au clusters is presented. The peptide-Au clusters exhibit red emission (λ(em) = 677 nm) and specifically stain the nuclei of three cell lines.

Ag cluster–aptamer hybrid: specifically marking the nucleus of live cells

Silver cluster-aptamer hybrids were mineralized via an artificially designed aptamer. The hybrids gave red emission when excited by light, and they successfully targeted the nucleus of live cells. This method is an effective approach to make cell target probes.

Graphene Covalently Binding Aryl Groups: Conductivity Increases Rather than Decreases

Graphene functionalized via nitrophenyl groups covalently bonding to its basal plane is studied by Raman spectroscopy and electric transport measurements. The Raman spectra of functionalized graphene exhibit D mode and peaks derived from nitrophenyl groups, and the two fingerprints exhibit nearly the same distribution in the two-dimensional Raman maps over the whole graphene sheet. This result directly proves that the nitrophenyl groups bond to the graphene basal plane via σ-bonds. Electric transport measurements demonstrate that the modified graphene is significantly more conductive than intrinsic graphene. In the competition between charge transfer effect and scattering effect introduced by the nitrophenyl groups, the former one is dominant so that the conductivity of functionalized graphene is significantly enhanced as a result.

Diazonium Functionalized Graphene: Microstructure, Electric, and Magnetic Properties

The unique honeycomb lattice structure of graphene gives rise to its outstanding electronic properties such as ultrahigh carrier mobility, ballistic transport, and more. However, a crucial obstacle to its use in the electronics industry is its lack of an energy bandgap. A covalent chemistry strategy could overcome this problem, and would have the benefits of being highly controllable and stable in the ambient environment. One possible approach is aryl diazonium functionalization. In this Account, we investigate the micromolecular/lattice structure, electronic structure, and electron-transport properties of nitrophenyl-diazonium-functionalized graphene. We find that nitrophenyl groups mainly adopt random and inhomogeneous configurations on the graphene basal plane, and that their bonding with graphene carbon atoms leads to slight elongation of the graphene lattice spacing. By contrast, hydrogenated graphene has a compressed lattice. Low levels of functionalization suppressed the electric conductivity of the resulting functionalized graphene, while highly functionalized graphene showed the opposite effect. This difference arises from the competition between the charge transfer effect and the scattering enhancement effect introduced by nitrophenyl groups bonding with graphene carbon atoms. Detailed electron transport measurements revealed that the nitrophenyl diazonium functionalization locally breaks the symmetry of graphene lattice, which leads to an increase in the density of state near the Fermi level, thus increasing the carrier density. On the other hand, the bonded nitrophenyl groups act as scattering centers, lowering the mean free path of the charge carriers and suppressing the carrier mobility. In rare cases, we observed ordered configurations of nitrophenyl groups in local domains on graphene flakes due to fluctuations in the reaction processes. We describe one example of such a superlattice, with a lattice constant nearly twice of that of pristine graphene. We performed comprehensive theoretical calculations to investigate the lattice and the electronic structure of the superlattice structure. Our results reveal that it is a thermodynamically stable, spin-polarized semiconductor with a bandgap of ∼0.5 eV. Our results demonstrate the possibility of controlling graphenes electronic properties using aryl diazonium functionalization. Asymmetric addition of aryl groups to different sublattices of graphene is a promising approach for producing ferromagnetic, semiconductive graphene, which will have broad applications in the electronic industry.

The Strong MRI Relaxivity of Paramagnetic Nanoparticles

We developed a method to synthesize paramagnetic nanoparticles of Gd@C82(OH)22+/-2. Such nanoparticles are with ordered microstructures and have strong MRI proton relaxation in vitro/vivo. Compared with commercial Gd-DTPA, a 12x MRI relaxivity of Gd@C82(OH)22+/-2 nanoparticles with ordered microstructures was achieved in vitro. The small Gd@C82(OH)22+/-2 nanoparticles, approximately 65nm, could easily escape the RES uptake in vivo; this opens the door for their clinical applications.